CD4 responses in the setting or suboptimal virological responses to antiretroviral therapy: features, outcomes, and associated factors.

PubMed

Collazos, Julio; Asensi, Víctor; Cartón, José Antonio

2009-07-01

The factors associated with discordant viroimmunological responses following antiretroviral therapy are unclear. We studied 1380 patients who initiated a protease inhibitor (PI)-based antiretroviral regimen and who fulfilled the criteria for inclusion. Of them, 255 (18.5%) had CD4 increases > or =100 cells/microl after 1 year of therapy despite detectable viral load (immunological responders); they were compared with 669 patients (48.5%) who had CD4 increases <100 cells/microl regardless of their final viral load (immunological nonresponders). Immunological responders had higher rates of sexual acquisition of HIV (p = 0.03), lower rates of clinical progression (p = 0.02), higher probabilities of being naive to antiretroviral therapy (p = 0.006) or to PI if antiretroviral experienced (p = 0.03), higher rates of receiving only nucleoside reverse transcriptase inhibitors in addition to the PI (p = 0.04), and lower baseline CD4 counts (p = 0.007) and higher viral loads (p = 0.009), as compared with nonresponders. Multivariate analysis revealed that sexual transmission of HIV (homosexual p = 0.004, heterosexual p = 0.03), no prior PI experience (p = 0.005), absence of clinical progression (p = 0.02), and lower baseline CD4 counts (p = 0.03) were independently associated with immunological response. However, these factors differed according to the patients' prior antiretroviral status, as higher baseline viral load was also associated with immunological response in antiretroviral-experienced patients (p = 0.02), whereas baseline CD4 count (p = 0.007) was the only predictive parameter in antiretroviral-naive patients. We conclude that immunological responses despite suboptimal viral suppression are common. Prior PI experience, HIV transmission category, baseline CD4 counts, and clinical progression were independently predictive of this condition, although the associated factors were different depending on the patient's prior antiretroviral history.

Effect of age on immunological response in the first year of antiretroviral therapy in HIV-1-infected adults in West Africa.

PubMed

Balestre, Eric; Eholié, Serge P; Lokossue, Amani; Sow, Papa Salif; Charurat, Man; Minga, Albert; Drabo, Joseph; Dabis, François; Ekouevi, Didier K; Thiébaut, Rodolphe

2012-05-15

To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context. The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4 gain over 12 months of ART was estimated using linear mixed models. Models were adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar period and ART regimen. The total number of patients included was 24,107, contributing for 50,893 measures of CD4 cell count in the first year of ART. The baseline median CD4 cell count was 144 cells/μl [interquartile range (IQR) 61-235]; median CD4 cell count reached 310 cells/μl (IQR 204-443) after 1 year of ART. The median age at treatment initiation was 36.3 years (10th-90th percentiles = 26.5-50.1). In adjusted analysis, the mean CD4 gain was significantly higher in younger patients (P < 0.0001). At 12 months, patients below 30 years recovered an additional 22 cells/μl on average [95% confidence interval (CI) 2-43] compared to patients at least 50 years. Among HIV-infected adults in West Africa, the immunological response after 12 months of ART was significantly poorer in elderly patients. As the population of treated patients is likely to get older, the impact of this age effect on immunological response to ART may increase over time.

Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study.

PubMed

Azzoni, Livio; Foulkes, Andrea S; Firnhaber, Cynthia; Yin, Xiangfan; Crowther, Nigel J; Glencross, Deborah; Lawrie, Denise; Stevens, Wendy; Papasavvas, Emmanouil; Sanne, Ian; Montaner, Luis J

2011-07-29

The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution.

CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV

PubMed Central

Lewis, Dorothy E; Gross, Kimber L; Diez, Martine M; Martinez, Maria L; Lukefahr, Helen N; Kozinetz, Claudia A; Arduino, Roberto C

2007-01-01

Background As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8+ T cell death in responses to ART and IL-2 therapy. Methods Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses. Results Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4+ T cells, leading to an increase in CD4 cell counts. CD8+ T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% ± 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8+ T cell apoptosis at baseline (mean 2.2% ± 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8+ T cell apoptosis (mean CD4 cell counts 1,209 ± 164 vs 754 ± 320 cells/mm3; CD4:CD8 ratios 1.55 vs. 0.70, respectively). Conclusion We postulate that CD8+ T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4+ T cells to rebound. Levels of CD8+ T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study. PMID:17263884

CD8 apoptosis may be a predictor of T cell number normalization after immune reconstitution in HIV.

PubMed

Lewis, Dorothy E; Gross, Kimber L; Diez, Martine M; Martinez, Maria L; Lukefahr, Helen N; Kozinetz, Claudia A; Arduino, Roberto C

2007-01-30

As part of the Houston Vanguard study, a subset of 10 patients randomized to receive IL-2 therapy were compared to 4 patients randomized to not receive IL-2, for markers of T cell activation and death during the first three cycles of IL-2. All patients were treated with combination antiretroviral therapy (ART) and were virally suppressed. The purpose of the study was to examine the role of CD8(+) T cell death in responses to ART and IL-2 therapy. Lymphocytes were examined at Day 0, 5 and 30 days during three cycles of IL-2 therapy. CD25, CD38, HLA-DR expression and annexin (cell death) were examined on CD4 and CD8 subpopulations. Follow up studies examined CD4 levels and CD4:CD8 reconstitution after 6 years using both univariant and multivariate analyses. Human lymphocytes responded to IL-2 therapy by upregulation of CD25 on CD4(+) T cells, leading to an increase in CD4 cell counts. CD8(+) T cells did not increase CD25 expression, but upregulated activation antigens (CD38 and DR) and had increased death. At baseline, 7 of the 14 patients had high CD8+ T cell apoptosis (mean 17.0% +/- 6.0). We did an exploratory analysis of immune status after six years, and found that baseline CD8+ T cell apoptosis was correlated with CD4 cell count gain beginning two years post enrollment. Patients with low levels of CD8(+) T cell apoptosis at baseline (mean 2.2% +/- 2.1) had significantly higher CD4 cell counts and more normalized CD4:CD8 ratios than patients with high CD8(+) T cell apoptosis (mean CD4 cell counts 1,209 +/- 164 vs 754 +/- 320 cells/mm(3); CD4:CD8 ratios 1.55 vs. 0.70, respectively). We postulate that CD8(+) T cell apoptosis may reflect inherent activation status, which continues in some patients even though viral replication is suppressed which influences the ability of CD4(+) T cells to rebound. Levels of CD8(+) T cell apoptosis may therefore be an independent predictor of immune status, which should be shown in a prospective study.

Discordant Treatment Responses to Combination Antiretroviral Therapy in Rwanda: A Prospective Cohort Study

PubMed Central

Kayigamba, Felix R.; Franke, Molly F.; Bakker, Mirjam I.; Rodriguez, Carly A.; Bagiruwigize, Emmanuel; Wit, Ferdinand WNM; Rich, Michael L.; Schim van der Loeff, Maarten F.

2016-01-01

Introduction Some antiretroviral therapy naïve patients starting combination antiretroviral therapy (cART) experience a limited CD4 count rise despite virological suppression, or vice versa. We assessed the prevalence and determinants of discordant treatment responses in a Rwandan cohort. Methods A discordant immunological cART response was defined as an increase of <100 CD4 cells/mm3 at 12 months compared to baseline despite virological suppression (viral load [VL] <40 copies/mL). A discordant virological cART response was defined as detectable VL at 12 months with an increase in CD4 count ≥100 cells/mm3. The prevalence of, and independent predictors for these two types of discordant responses were analysed in two cohorts nested in a 12-month prospective study of cART-naïve HIV patients treated at nine rural health facilities in two regions in Rwanda. Results Among 382 patients with an undetectable VL at 12 months, 112 (29%) had a CD4 rise of <100 cells/mm3. Age ≥35 years and longer travel to the clinic were independent determinants of an immunological discordant response, but sex, baseline CD4 count, body mass index and WHO HIV clinical stage were not. Among 326 patients with a CD4 rise of ≥100 cells/mm3, 56 (17%) had a detectable viral load at 12 months. Male sex was associated with a virological discordant treatment response (P = 0.05), but age, baseline CD4 count, BMI, WHO HIV clinical stage, and travel time to the clinic were not. Conclusions Discordant treatment responses were common in cART-naïve HIV patients in Rwanda. Small CD4 increases could be misinterpreted as a (virological) treatment failure and lead to unnecessary treatment changes. PMID:27438000

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care

PubMed Central

Cescon, Angela; Patterson, Sophie; Davey, Colin; Ding, Erin; Raboud, Janet M; Chan, Keith; Loutfy, Mona R; Cooper, Curtis; Burchell, Ann N; Palmer, Alexis K; Tsoukas, Christos; Machouf, Nima; Klein, Marina B; Rourke, Sean B; Rachlis, Anita; Hogg, Robert S; Montaner, Julio SG

2015-01-01

Introduction Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. Methods Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm3 or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran–Armitage test, and independent correlates of late initiation were identified using logistic regression. Results In total, 8942 participants (18% female) of median age 40 years (Q1–Q3 33–47) were included. The median baseline CD4 count increased from 190 cells/mm3 (Q1–Q3 80–320) in 2000 to 360 cells/mm3 (Q1–Q3 220–490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm3 or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm3), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation. Conclusions This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care. PMID:26443752

Late initiation of combination antiretroviral therapy in Canada: a call for a national public health strategy to improve engagement in HIV care.

PubMed

Cescon, Angela; Patterson, Sophie; Davey, Colin; Ding, Erin; Raboud, Janet M; Chan, Keith; Loutfy, Mona R; Cooper, Curtis; Burchell, Ann N; Palmer, Alexis K; Tsoukas, Christos; Machouf, Nima; Klein, Marina B; Rourke, Sean B; Rachlis, Anita; Hogg, Robert S; Montaner, Julio S G

2015-01-01

Combination antiretroviral therapy (ART) significantly decreases morbidity, mortality and HIV transmission. We aimed to characterize the timing of ART initiation based on CD4 cell count from 2000 to 2012 and identify factors associated with late initiation of treatment. Participants from the Canadian Observational Cohort (CANOC), a multi-site cohort of HIV-positive adults initiating ART naively after 1 January 2000, in three Canadian provinces (British Columbia, Ontario and Québec) were included. Late initiation was defined as a CD4 count <200 cells/mm(3) or an AIDS-defining illness before ART initiation (baseline). Temporal trends were assessed using the Cochran-Armitage test, and independent correlates of late initiation were identified using logistic regression. In total, 8942 participants (18% female) of median age 40 years (Q1-Q3 33-47) were included. The median baseline CD4 count increased from 190 cells/mm(3) (Q1-Q3 80-320) in 2000 to 360 cells/mm(3) (Q1-Q3 220-490) in 2012 (p<0.001). Overall, 4274 participants (48%) initiated ART with a CD4 count <200 cells/mm(3) or AIDS-defining illness. Late initiation was more common among women, non-MSM, older individuals, participants from Ontario and BC (vs. Québec), persons with injection drug use (IDU) history and individuals starting ART in earlier calendar years. In sub-analysis exploring recent (2008 to 2012) predictors using an updated CD4 criterion (<350 cells/mm(3)), IDU and residence in BC (vs. Québec) were no longer significant correlates of late initiation. This analysis documents increasing baseline CD4 counts over time among Canadians initiating ART. However, CD4 counts at ART initiation remain below contemporary treatment guidelines, highlighting the need for strategies to improve earlier engagement in HIV care.

Metabolic and anthropometric parameters contribute to ART-mediated CD4+ T cell recovery in HIV-1-infected individuals: an observational study

PubMed Central

2011-01-01

Background The degree of immune reconstitution achieved in response to suppressive ART is associated with baseline individual characteristics, such as pre-treatment CD4 count, levels of viral replication, cellular activation, choice of treatment regimen and gender. However, the combined effect of these variables on long-term CD4 recovery remains elusive, and no single variable predicts treatment response. We sought to determine if adiposity and molecules associated with lipid metabolism may affect the response to ART and the degree of subsequent immune reconstitution, and to assess their ability to predict CD4 recovery. Methods We studied a cohort of 69 (48 females and 21 males) HIV-infected, treatment-naïve South African subjects initiating antiretroviral treatment (d4T, 3Tc and lopinavir/ritonavir). We collected information at baseline and six months after viral suppression, assessing anthropometric parameters, dual energy X-ray absorptiometry and magnetic resonance imaging scans, serum-based clinical laboratory tests and whole blood-based flow cytometry, and determined their role in predicting the increase in CD4 count in response to ART. Results We present evidence that baseline CD4+ T cell count, viral load, CD8+ T cell activation (CD95 expression) and metabolic and anthropometric parameters linked to adiposity (LDL/HDL cholesterol ratio and waist/hip ratio) significantly contribute to variability in the extent of CD4 reconstitution (ΔCD4) after six months of continuous ART. Conclusions Our final model accounts for 44% of the variability in CD4+ T cell recovery in virally suppressed individuals, representing a workable predictive model of immune reconstitution. PMID:21801351

Structural normalization of the lymphoid tissue in asymptomatic HIV-infected patients after 48 weeks of potent antiretroviral therapy.

PubMed

Macías, J; Japón, M A; Leal, M; Sáez, C; Pineda, J A; Segura, D I; Ortega, J; Lissen, E

2001-12-07

The hallmark of HIV infection is the involution and destruction of lymphoid tissue. However, very little information exists on the effect of highly active antiretroviral therapy (HAART) on lymphoid tissue structure. To evaluate the effect of a HAART regimen after 48 weeks on the architecture and cell regeneration of tonsil lymphoid tissue in HIV-infected patients with CD4 T cell counts > or = 500/microl. From June 1997 to February 1998 all asymptomatic HIV-infected patients with CD4 T cell counts > or = 500/microl seen at our unit were offered quadruple antiretroviral therapy. Tonsil biopsies were obtained at baseline and at 48 weeks. Tonsil tissue sections were examined to evaluate structural and immunohistochemical changes by two blinded and independent pathologists. Cell numbers were counted for selected markers in T-dependent zones. Eleven patients were evaluable, six were excluded because of insufficient or inadequate sampling in at least one of the biopsies. Cellular depletion, plasma cell accumulation and prominent vessels were observed in all cases; three excluded patients with evaluable baseline biopsies showed similar tissue lesions. Follow-up biopsies demonstrated some degree of improvement in all patients. Germinal centres appeared in seven cases that were not seen at baseline. CD4 cell counts increased and CD8 cell counts decreased significantly in lymphoid tissue. An increase in CD45RA+ cells was observed; however, the proportion of CD45+Ki67+ cells did not differ between baseline and 48 weeks. This study shows an unexpected range of moderate to severe lymphoid tissue lesions in mildly immunosuppressed HIV-infected patients, which was partly restored after 48 weeks of HAART.

CD4/CD8 ratio, age, and risk of serious non-communicable diseases in HIV-infected adults on antiretroviral therapy

PubMed Central

CASTILHO, Jessica L.; SHEPHERD, Bryan E.; KOETHE, John; TURNER, Megan; BEBAWY, Sally; LOGAN, James; ROGERS, William B.; RAFFANTI, Stephen; STERLING, Timothy R.

2015-01-01

Objective In virologically suppressed HIV-infected adults, non-communicable diseases (NCDs) have been associated with immune senescence and low CD4/CD8 lymphocyte ratio. Age differences in the relationship between CD4/CD8 ratio and NCDs have not been described. Design Observational cohort study. Methods We assessed CD4/CD8 ratio and incident NCDs (cardiovascular, cancer, liver, and renal diseases) in HIV-infected adults started on antiretroviral therapy between 1998–2012. Study inclusion began once patients maintained virologic suppression for 12 months (defined as baseline). We examined age and baseline CD4/CD8 ratio and used Cox proportional hazard models to assess baseline CD4/CD8 ratio and NCDs. Results This study included 2,006 patients. Low baseline CD4/CD8 ratio was associated with older age, male sex, and low CD4 lymphocyte counts. In models adjusting for CD4 lymphocyte count, CD4/CD8 ratio was inversely associated with age (p <0.01). Among all patients, 182 had incident NCDs, including 46 with coronary artery disease (CAD) events. CD4/CD8 ratio was inversely associated with risk of CAD events (adjusted HR per 0.1 increase in CD4/CD8 ratio = 0.87, 95% CI: 0.76–0.99, p=0.03). This association was driven by those under age 50 years (adjusted HR 0.83 [0.70–0.97], p = 0.02) versus those over age 50 years (adjusted HR = 0.96 [0.79–1.18], p = 0.71). CD4/CD8 ratio was not significantly associated with incident non-cardiac NCDs. Conclusions Higher CD4/CD8 ratio after one year of HIV virologic suppression was independently predictive of decreased CAD risk, particularly among younger adults. Advanced immune senescence may contribute to CAD events in younger HIV patients on antiretroviral therapy. PMID:26959354

No effect of interleukin-2 on IgE levels given in addition to antiretroviral therapy in HIV-infected adults with CD4 >300 cells/mm3.

PubMed

Ananworanich, Jintanat; Chantaphakul, Hiroshi; Teeratakulpisarn, Somsong; Siangphoe, Umaporn; Ubolyam, Sasiwimol; Chuenyam, Theshinee; Ungsedhaphan, Chaiwat; Lange, Joep; Cooper, David; Phanuphak, Praphan; Ruxrungtham, Kiat

2005-03-01

HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and Th2 cytokines. The objective of the present study was to investigate whether IL-2 given in addition to antiretrovirals (ARV) would result in lower IgE levels and less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom scoring, PFT and skin prick test (SPT) were performed. It was found that the baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively. Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1 antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the baseline; however, there were no differences in IgE levels, allergic symptom scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect on atopy.

Daily low-dose subcutaneous interleukin-2 added to single- or dual-nucleoside therapy in HIV infection does not protect against CD4+ T-cell decline or improve other indices of immune function: results of a randomized controlled clinical trial (ACTG 248).

PubMed

Vogler, Mary A; Teppler, Hedy; Gelman, Rebecca; Valentine, Fred; Lederman, Michael M; Pomerantz, Roger J; Pollard, Richard B; Cherng, Deborah Weng; Gonzalez, Charles J; Squires, Kathleen E; Frank, Ian; Mildvan, Donna; Mahon, Laura F; Schock, Barbara

2004-05-01

Approaches to preserve or enhance immune function in HIV-1 infection are needed. To examine the ability of daily low-dose interleukin-2 (IL-2) in combination with antiretroviral therapy to preserve circulating CD4+ T-cell counts, the clinical safety and tolerability of this treatment, and safety with respect to changes in plasma HIV-1 RNA levels. Twenty-four-week, phase 2, multicenter, randomized, open-label trial conducted at 12 AIDS Clinical Trials Units between September 1995 and May 1997. A total of 115 HIV-infected persons with screening CD4+ T-cell counts between 300 and 700 cells/mm who were on stable single- or dual-nucleoside therapy for at least 2 months, 11% of whom were also on a protease inhibitor at study entry. Patients were randomly assigned to receive IL-2 at a dose of 1 million IU subcutaneously once daily plus continued anti-retroviral therapy (ART + IL-2, n = 57) vs. continued ART alone (ART alone, n = 58). IL-2 dose reductions were made for objective or subjective toxicities. All subjects randomly assigned to the IL-2 arm who interrupted ART were also required to discontinue IL-2 for the same period. The primary endpoint was a decrease in CD4 T-cell count from baseline; the safety analysis was based on change in plasma HIV RNA by bDNA; and clinical safety and tolerability were analyzed by standard clinical criteria. Of the patients with a baseline CD4 T-cell count recorded, 15 (27%) of 55 patients randomly assigned to ART alone had a drop of > or =25% in their CD4 T-cell count and 23 (41%) of 56 patients randomly assigned to ART + IL-2 had a drop of > or =25% in their CD4 T-cell count at some time over the 24 weeks of the study. This difference was not statistically significant. There was a statistically significant greater variance in CD4 T-cell counts in the IL-2-treated group. More patients in the IL-2 group had at least a 25% increase in CD4 T-cell counts over baseline (34 vs. 13%, P = 0.007). A comparison of grade 3 or worse toxicity showed no differences between the arms, but IL-2 was associated with significantly more grade 2 or worse general body symptoms, primarily discomfort and fatigue. There was no significant difference between the groups with regard to changes in plasma HIV RNA, lymphocyte proliferation, natural killer cell activity, skin test responses to recall antigens, or antibody responses to immunization. Plasma markers of immune activation all increased significantly in IL-2 recipients. In patients with baseline CD4 T-cell counts > or =300 cells/mm primarily treated with single- or dual-nucleoside ART, subcutaneously administered IL-2 at a dose of 1 million IU daily for up to 24 weeks had low toxicity but showed no consistent benefit in preventing decline in CD4 T-cell counts and minimal evidence of immunologic improvement vs. continued ART alone.

Plasma n-6 Fatty Acid Levels Are Associated With CD4 Cell Counts, Hospitalization, and Mortality in HIV-Infected Patients.

PubMed

Kabagambe, Edmond K; Ezeamama, Amara E; Guwatudde, David; Campos, Hannia; Fawzi, Wafaie

2016-12-15

Fatty acids, including n-6 series, modulate immune function, but their effect on CD4 cell counts, death, or hospitalization in HIV-infected patients on antiretroviral therapy is unknown. In a randomized trial for effects of multivitamins in HIV-infected patients in Uganda, we used gas chromatography to measure plasma n-6 fatty acids at baseline; determined CD4 counts at baseline, 3, 6, 12, and 18 months; and recorded hospitalization or death events. The associations of fatty acids with CD4 counts and events were analyzed using repeated-measures analysis of variance and Cox regression, respectively. Among 297 patients with fatty acids measurements, 16 patients died and 69 were hospitalized within 18 months. Except for linoleic acid, n-6 fatty acids levels were positively associated with CD4 counts at baseline but not during follow-up. In models that included all 5 major n-6 fatty acids, age; sex; body mass index; anemia status; use of antiretroviral therapy, multivitamin supplements, and alcohol; and the risk of death or hospitalization decreased significantly with an increase in linoleic acid and gamma-linolenic acid levels, whereas associations for dihomo-gamma-linolenic acid, arachidonic acid, and aolrenic acid were null. The hazard ratios (95% confidence intervals) per 1 SD increase in linoleic acid and gamma-linolenic acid were 0.73 (0.56-0.94) and 0.51 (0.36-0.72), respectively. Gamma-linolenic acid remained significant (hazard ratio = 0.51; 95% confidence interval: 0.35 to 0.68) after further adjustment for other plasma fatty acids. Lower levels of gamma-linolenic acid are associated with lower CD4 counts and an increased risk of death or hospitalization. These results suggest a potential for using n-6 fatty acids to improve outcomes from antiretroviral therapy.

Treatment outcomes of patients on antiretrovirals after six months of treatment, Khami Clinic, Bulawayo, Zimbabwe.

PubMed

Ncube, R T; Hwalima, Z; Tshimanga, M; Chirenda, J; Mabaera, B; Apollo, T

2008-01-01

To describe treatment outcomes of patients on anti-retrovirals at six months of treatment. We conducted pre-intervention post intervention surveys using a pretest-post test design. Khami Municipal Clinic, Bulawayo. We interviewed consecutive patients eligible to receive antiretroviral drugs (ARVs). All patients had a history of TB treatment and a CD4 count less than 200 cells/mm. Mean change in CD4 count, weight, body mass index, and Karnofsky performance measured before and at six months ofantiretroviral treatment. 72 subjects were interviewed at baseline, their median age was 38 years (Q1, 32 years, Q3, 43 years). Of these, 17 (24%) died before six months of treatment. Three (4%) defaulted treatment follow up. A total of 52 respondents were alive and interviewed at six months though only 50, had repeat CD4 counts at six months. Among the 50 survivors, the mean CD4 count at six months was significantly higher than at baseline (p = 0.0003). There was a 4.2 point statistical significant increase in the mean weight from baseline (p = 0.0005). Similarly, the mean Body Mass Index (BMI) significantly increased by 1.5 kg/m2 from baseline, (p = 0.001). The mean Karnofsky performance increased from 89% at baseline to 95% at six months (p = 0004). The researchers noted that patients on TB treatment were being deferred antiretroviral therapy until they completed TB treatment. The Khami project bears testimony that even in a resource poor setting; treatment of HIV/AIDS with antiretroviral drugs is feasible. We recommend early treatment initiation for those on TB treatment in line with national guidelines.

Maternal outcomes after HAART for the prevention of mother-to-child transmission in HIV-infected women in Brazil.

PubMed

Pilotto, Jose H; Velasque, Luciane S; Friedman, Ruth K; Moreira, Ronaldo I; Veloso, Valdilea G; Grinsztejn, Beatriz; Morgado, Mariza G; Watts, D Heather; Currier, Judith S; Hoffman, Risa M

2011-01-01

Information is lacking on outcomes in HIV-infected Brazilian women with CD4(+) T-cell counts >200 cells/mm(3) who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery. Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2-3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4(+) T-cell decrease to ≤200 cells/mm(3). Predictors of the WHO stage 2-3 events and HIV progression outcomes were evaluated with Cox's proportional hazards models. A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2-3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8-20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3-11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4(+) T-cell decreases. Women who had baseline CD4(+) T-cell counts between 200-500 cells/mm(3) had a hazard ratio for WHO stage 2-3 events of 2.5 compared to women with baseline ≥500 cells/mm(3) (95% CI 1.0-6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4(+) T-cell count (hazard ratio 0.99, 95% CI 0.98-0.99; P=0.02). In this observational study, a baseline CD4(+) T-cell count <500 cells/mm(3) was associated with an increased risk of postpartum WHO stage 2-3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health.

The effect of valacyclovir on HIV and HSV-2 in HIV-infected persons on antiretroviral therapy with previously unrecognised HSV-2.

PubMed

Van Wagoner, Nicholas; Geisler, William M; Bachmann, Laura H; Hook, Edward W

2015-07-01

In the absence of antiretroviral therapy, valacyclovir may reduce HIV viral load and increase CD4+ T-lymphocyte count. We sought to evaluate the impact of valacyclovir on HIV and HSV-2 in co-infected patients receiving antiretroviral therapy with previously unrecognised HSV-2 infection. A prospective, randomised-controlled, 24-week trial of valacyclovir 1000 mg was performed. Mean CD4+ T-lymphocyte count at 24 weeks compared to baseline CD4+ T-lymphocyte count was the primary outcome. HIV viral load suppression, HSV-2 outbreaks and asymptomatic HSV-2 shedding were secondary outcomes. Participants were randomised to valacyclovir (N = 66) or placebo (N = 35). Study completion was 64%. There was no change in 24 weeks compared to baseline CD4+ T-lymphocyte count in either group (valacyclovir p = 0.91, placebo p = 0.59) or the proportion with HIV viral load suppression (valacyclovir p = 0.75, placebo p = 1.0). Genital HSV and asymptomatic HSV-2 shedding were rare. Valacyclovir had no effect on CD4+ T-lymphocyte count or HIV viral load in this population. Valacyclovir may reduce clinical outbreaks and asymptomatic HSV-2 shedding, but the rarity of these events, along with its lack of benefit on HIV, does not support its use in this clinical setting. © The Author(s) 2014.

No neurocognitive advantage for immediate antiretroviral treatment in adults with greater than 500 CD4+ T-cell counts.

PubMed

Wright, Edwina J; Grund, Birgit; Robertson, Kevin R; Cysique, Lucette; Brew, Bruce J; Collins, Gary L; Poehlman-Roediger, Mollie; Vjecha, Michael J; Penalva de Oliveira, Augusto César; Standridge, Barbara; Carey, Cate; Avihingsanon, Anchalee; Florence, Eric; Lundgren, Jens D; Arenas-Pinto, Alejandro; Mueller, Nicolas J; Winston, Alan; Nsubuga, Moses S; Lal, Luxshimi; Price, Richard W

2018-05-15

To compare the effect of immediate versus deferred antiretroviral treatment (ART) on neuropsychological test performance in treatment-naive HIV-positive adults with more than 500 CD4 cells/μl. Randomized trial. The START parent study randomized participants to commence immediate versus deferred ART until CD4 less than 350 cells/μl. The START Neurology substudy used eight neuropsychological tests, at baseline, months 4, 8, 12 and annually, to compare groups for changes in test performance. Test results were internally standardized to z-scores. The primary outcome was the average of the eight test z-scores (QNPZ-8). Mean changes in QNPZ-8 from baseline were compared by intent-to-treat using longitudinal mixed models. Changes from baseline to specific time points were compared using ANCOVA models. The 592 participants had a median age of 34 years; median baseline CD4 count was 629 cells/μl; the mean follow-up was 3.4 years. ART was used for 94 and 32% of accrued person-years in the immediate and deferred groups, respectively. There was no difference between the immediate and deferred ART groups in QNPZ-8 change through follow-up [-0.018 (95% CI -0.062 to 0.027, P = 0.44)], or at any visit. However, QNPZ-8 scores increased in both arms during the first year, by 0.22 and 0.24, respectively (P < 0.001 for increase from baseline). We observed substantial improvement in neurocognitive test performance during the first year in both study arms, underlining the importance of using a control group in studies assessing neurocognitive performance over time. Immediate ART neither benefitted nor harmed neurocognitive performance in individuals with CD4 cell counts above 500 cells/μl.

Changes in intestinal microbiota in HIV-1-infected subjects following cART initiation: influence of CD4+ T cell count.

PubMed

Ji, Yongjia; Zhang, Fengdi; Zhang, Renfang; Shen, Yinzhong; Liu, Li; Wang, Jiangrong; Yang, Junyang; Tang, Qi; Xun, Jingna; Qi, Tangkai; Wang, Zhenyan; Song, Wei; Tang, Yang; Chen, Jun; Lu, Hongzhou

2018-06-22

The roles of immunodeficiency and combined antiretroviral therapy (cART) in shaping the gut microbiota in HIV-1-infected subjects (HISs) have not been described thoroughly by time-series investigations. In this study, 36 antiretroviral-naïve HISs were enrolled to prospectively assess alterations in the fecal microbiota and plasma markers of microbial translocation and inflammation with cART. At baseline, the species α-diversity of the fecal microbiota was significantly lower in HISs with a CD4 + T cell count <300/mm 3 than in HISs with a CD4 + T cell count >300/mm 3 (Shannon index: Median 2.557 vs. 2.981, P = 0.006; Simpson index: Median 0.168 vs. 0.096, P = 0.004). Additionally, the baseline α-diversity indices correlated with CD4 + T cell counts (Shannon index: r = 0.474, P = 0.004; Simpson index: r = -0.467, P = 0.004) and the specific plasma biomarkers for microbial translocation and inflammation. After cART introduction, the species α-diversity of fecal microbiota in HISs with CD4 + T cell counts <300/mm 3 was significantly restored (Shannon index: Median 2.557 vs. 2.791, P = 0.007; Simpson index: Median 0.168 vs. 0.112, P = 0.004), while the variances were insignificant among HISs with CD4+ T cell counts >300/mm 3 (Shannon index: Median 2.981 vs. 2.934, P = 0.179; Simpson index: Median 0.096 vs. 0.119, P = 0.082). Meanwhile, with cART introduction, alterations in the gut microbial composition were more significant in the subgroup with CD4 + T cell counts >300/mm 3 , corresponding to increases in the specific plasma inflammatory markers. These findings implicated the interactive roles of immunodeficiency and cART for affecting gut microbiota in HIV-1-infected individuals, providing new insights into intestinal microbiome dysbiosis related to HIV-1 infection.

CD4+ Cell Count and HIV Load as Predictors of Size of Anal Warts Over Time in HIV-Infected Women

PubMed Central

Luu, Hung N.; Amirian, E. Susan; Chan, Wenyaw; Beasley, R. Palmer; Piller, Linda B.

2012-01-01

Background. Little is known about the associations between CD4+ cell counts, human immunodeficiency virus (HIV) load, and human papillomavirus “low-risk” types in noncancerous clinical outcomes. This study examined whether CD4+ count and HIV load predict the size of the largest anal warts in 976 HIV-infected women in an ongoing cohort. Methods. A linear mixed model was used to determine the association between size of anal wart and CD4+ count and HIV load. Results. The incidence of anal warts was 4.15 cases per 100 person-years (95% confidence interval [CI], 3.83–4.77) and 1.30 cases per 100 person-years (95% CI, 1.00–1.58) in HIV-infected and HIV-uninfected women, respectively. There appeared to be an inverse association between size of the largest anal warts and CD4+ count at baseline; however, this was not statistically significant. There was no association between size of the largest anal warts and CD4+ count or HIV load over time. Conclusions. There was no evidence for an association between size of the largest anal warts and CD4+ count or HIV load over time. Further exploration on the role of immune response on the development of anal warts is warranted in a larger study. PMID:22246682

AZT Impairs Immunological Recovery on First-line ART: Collaborative analysis of cohort studies in Southern Africa

PubMed Central

WANDELER, Gilles; GSPONER, Thomas; MULENGA, Lloyd; GARONE, Daniela; WOOD, Robin; MASKEW, Mhairi; PROZESKY, Hans; HOFFMANN, Christopher; EHMER, Jochen; DICKINSON, Diana; DAVIES, Mary-Ann; EGGER, Matthias; KEISER, Olivia

2013-01-01

Objectives Zidovudine (AZT) is recommended for first-line antiretroviral therapy (ART) in resource limited settings. AZT may, however, lead to anemia and impaired immunological response. We compared CD4 counts over 5 years between patients starting ART with and without AZT in Southern Africa. Design Cohort study Methods Patients aged ≥16 years who started first-line ART in South Africa, Botswana, Zambia or Lesotho were included. We used linear mixed-effect models to compare CD4 cell count trajectories between patients on AZT-containing regimens and patients on other regimens, censoring follow-up at first treatment change. Impaired immunological recovery, defined as a CD4 count below 100 cells/μl at 1 year, was assessed in logistic regression. Analyses were adjusted for baseline CD4 count and haemoglobin level, age, gender, type of regimen, viral load monitoring and calendar year. Results 72,597 patients starting ART, including 19,758 (27.2%) on AZT, were analysed. Patients on AZT had higher CD4 cell counts (150 vs.128 cells/μl) and haemoglobin level (12.0 vs. 11.0 g/dl) at baseline, and were less likely to be female than those on other regimens. Adjusted differences in CD4 counts between regimens containing and not containing AZT were −16 cells/μl (95% CI −18 to −14) at 1 year and −56 cells/μl (95% CI −59 to −52) at 5 years. Impaired immunological recovery was more likely with AZT compared to other regimens (odds ratio 1.40, 95% CI 1.22–1.61). Conclusions In Southern Africa AZT is associated with inferior immunological recovery compared to other backbones. Replacing AZT with another NRTI could avoid unnecessary switches to second-line ART. PMID:23660577

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults.

PubMed

Stermole, Benjamin M; Grandits, Greg A; Roediger, Mollie P; Clark, Brychan M; Ganesan, Anuradha; Weintrob, Amy C; Crum-Cianflone, Nancy F; Ferguson, Tomas M; Macalino, Grace E; Landrum, Michael L

2011-04-05

We analyzed HIV viral load (VL) and CD4 count changes, and antibody responses following MMR vaccination of individuals in the U.S. Military HIV Natural History Study cohort. Cases receiving at least one dose of MMR vaccine after HIV diagnosis were matched 1:2 to HIV-positive controls not receiving the vaccine. Baseline was defined as time of vaccination for cases and indexed and matched to the time post-HIV diagnosis for controls. Changes in CD4 count and VL at 6, 12, 18 and 24 months were compared between cases and controls using a general linear model. Available sera from cases were tested for MMR seropositivity at baseline and post-vaccination at 6, 12, 18, and 24 months. Overall mean CD4 count change from baseline through 24 months was 20 (±23) cells/μL greater for cases than controls (p=0.39). Similar non-significant changes in CD4 cell count were seen in the subset of those not on HAART at baseline. VL changes were small and similar between groups (mean differential change -0.04 (±0.18) log(10) copies/mL; p=0.84). Of 21 vaccinated participants with baseline serologic testing, 14 (67%) were reactive to measles, 19 (91%) to mumps, and 20 (95%) to rubella. Three (43%) of 7 participants nonreactive to measles developed measles IgG; for mumps, 1 (50%) of 2 developed mumps IgG; for rubella, 1 (100%) developed rubella IgG. MMR vaccination did not result in detrimental immunologic or virologic changes through 24 months post-vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

PubMed

Julg, Boris; Poole, Danielle; Ghebremichael, Musie; Castilla, Carmen; Altfeld, Marcus; Sunpath, Henry; Murphy, Richard A; Walker, Bruce D

2012-01-01

Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42%) and 83% (95% CI:79%-86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3) after 12 and ≥ 500 cells/mm(3) after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

PubMed Central

May, Margaret T.; Vehreschild, Jorg-Janne; Trickey, Adam; Obel, Niels; Reiss, Peter; Bonnet, Fabrice; Mary-Krause, Murielle; Samji, Hasina; Cavassini, Matthias; Gill, Michael John; Shepherd, Leah C.; Crane, Heidi M.; d'Arminio Monforte, Antonella; Burkholder, Greer A.; Johnson, Margaret M.; Sobrino-Vegas, Paz; Domingo, Pere; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy R.; Miró, José M.; Sterne, Jonathan A. C.

2016-01-01

Background. CD4 count at start of combination antiretroviral therapy (ART) is strongly associated with short-term survival, but its association with longer-term survival is less well characterized. Methods. We estimated mortality rates (MRs) by time since start of ART (<0.5, 0.5–0.9, 1–2.9, 3–4.9, 5–9.9, and ≥10 years) among patients from 18 European and North American cohorts who started ART during 1996–2001. Piecewise exponential models stratified by cohort were used to estimate crude and adjusted (for sex, age, transmission risk, period of starting ART [1996–1997, 1998–1999, 2000–2001], and AIDS and human immunodeficiency virus type 1 RNA at baseline) mortality rate ratios (MRRs) by CD4 count at start of ART (0–49, 50–99, 100–199, 200–349, 350–499, ≥500 cells/µL) overall and separately according to time since start of ART. Results. A total of 6344 of 37 496 patients died during 359 219 years of follow-up. The MR per 1000 person-years was 32.8 (95% confidence interval [CI], 30.2–35.5) during the first 6 months, declining to 16.0 (95% CI, 15.4–16.8) during 5–9.9 years and 14.2 (95% CI, 13.3–15.1) after 10 years’ duration of ART. During the first year of ART, there was a strong inverse association of CD4 count at start of ART with mortality. This diminished over the next 4 years. The adjusted MRR per CD4 group was 0.97 (95% CI, .94–1.00; P = .054) and 1.02 (95% CI, .98–1.07; P = .32) among patients followed for 5–9.9 and ≥10 years, respectively. Conclusions. After surviving 5 years of ART, the mortality of patients who started ART with low baseline CD4 count converged with mortality of patients with intermediate and high baseline CD4 counts. PMID:27025828

Evaluating immunologic response and clinical deterioration in treatment-naïve patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

PubMed Central

Oyomopito, Rebecca A.; Li, Patrick CK.; Sungkanuparph, Somnuek; Phanuphak, Praphan; Tee, Kok Keng; Sirisanthana, Thira; Kantipong, Pacharee; Oka, Shinichi; Lee, Chris KC.; Kamarulzaman, Adeeba; Choi, Jun Yong; Sohn, Annette H.; Law, Matthew; Chen, Yi-Ming A.

2012-01-01

Background HIV-1 group M viruses diverge 25%–35% in envelope, important for viral attachment during infection, and 10–15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunologic or virologic treatment responses differed by genotype in treatment-naïve patients initiating first-line therapy. Methods Prospectively collected, longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of CDC category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post-therapy, evaluated by linear and logistic regression, respectively. Results Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median:413 days, IQR:169–672 days). Patients >40 years demonstrated smaller immunological increases (p=0.002) and higher risk of clinical deterioration (HR=2.17; p=0.008). Patients with baseline CD4 cell counts >200 cells/μL had lower risk of clinical deterioration (HR=0.373; p=0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post-therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (p=0.024). A total of 530 patients (48.0% of eligible) were included in virologic analyses with no differences in response found between genotypes. Conclusions Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared to subtype-B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virologic suppression. PMID:23138836

Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.

PubMed

Tanuma, Junko; Matsumoto, Shoko; Haneuse, Sebastien; Cuong, Do Duy; Vu, Tuong Van; Thuy, Pham Thi Thanh; Dung, Nguyen Thi; Dung, Nguyen Thi Hoai; Trung, Nguyen Vu; Kinh, Nguyen Van; Oka, Shinichi

2017-12-01

Achieving viral suppression is key in the global strategy to end the HIV epidemic. However, the levels of viral suppression have yet to be described in many resource-limited settings. We investigated the time to virologic failure (VF; defined as a viral load of ≥1000 copies/ml) and changes in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired early immune recovery (defined as not attaining an increase in 100 cells/mm 3 in CD4 counts at 24 months) were further analysed. From 1806 participants, 225 were identified as having VF at a median of 50 months of first-line ART. The viral suppression rate at 12 months was 95.5% and survival without VF was maintained above 90% until 42 months. An increase in CD4 counts from the baseline was greater in groups with lower baseline CD4 counts. A younger age (multivariate hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR 1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT)) were associated with earlier VF. Factors associated with impaired early immune recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. Durable high-rate viral suppression was observed in the cohort of patients on first-line ART in Vietnam. Our results highlight the need to increase adherence support among injection drug users and HCV co-infected patients. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival

PubMed Central

Chen, Marcelo; Wong, Wing-Wai; Law, Matthew G.; Kiertiburanakul, Sasisopin; Yunihastuti, Evy; Merati, Tuti Parwati; Lim, Poh Lian; Chaiwarith, Romanee; Phanuphak, Praphan; Lee, Man Po; Kumarasamy, Nagalingeswaran; Saphonn, Vonthanak; Ditangco, Rossana; Sim, Benedict L. H.; Nguyen, Kinh Van; Pujari, Sanjay; Kamarulzaman, Adeeba; Zhang, Fujie; Pham, Thuy Thanh; Choi, Jun Yong; Oka, Shinichi; Kantipong, Pacharee; Mustafa, Mahiran; Ratanasuwan, Winai; Durier, Nicolas; Chen, Yi-Ming Arthur

2016-01-01

Background We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region. Methods Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test. Results A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive. Conclusion In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality. PMID:26933963

Is the virulence of HIV changing? A meta-analysis of trends in prognostic markers of HIV disease progression and transmission

PubMed Central

Herbeck, Joshua T.; Müller, Viktor; Maust, Brandon S.; Ledergerber, Bruno; Torti, Carlo; Di Giambenedetto, Simona; Gras, Luuk; Günthard, Huldrych F.; Jacobson, Lisa P.; Mullins, James I.; Gottlieb, Geoffrey S.

2013-01-01

Objective The potential for changing HIV-1 virulence has significant implications for the AIDS epidemic, including changing HIV transmission rates, rapidity of disease progression, and timing of ART. Published data to date have provided conflicting results. Design We conducted a meta-analysis of changes in baseline CD4+ T-cell counts and set point plasma viral RNA load over time in order to establish whether summary trends are consistent with changing HIV-1 virulence. Methods We searched PubMed for studies of trends in HIV-1 prognostic markers of disease progression and supplemented findings with publications referenced in epidemiological or virulence studies. We identified 12 studies of trends in baseline CD4+ T-cell counts (21 052 total individuals), and eight studies of trends in set point viral loads (10 785 total individuals), spanning the years 1984–2010. Using random-effects meta-analysis, we estimated summary effect sizes for trends in HIV-1 plasma viral loads and CD4+ T-cell counts. Results Baseline CD4+ T-cell counts showed a summary trend of decreasing cell counts [effect=−4.93 cells/µl per year, 95% confidence interval (CI) −6.53 to −3.3]. Set point viral loads showed a summary trend of increasing plasma viral RNA loads (effect=0.013 log10 copies/ml per year, 95% CI −0.001 to 0.03). The trend rates decelerated in recent years for both prognostic markers. Conclusion Our results are consistent with increased virulence of HIV-1 over the course of the epidemic. Extrapolating over the 30 years since the first description of AIDS, this represents a CD4+ T cells loss of approximately 148 cells/µl and a gain of 0.39 log10 copies/ml of viral RNA measured during early infection. These effect sizes would predict increasing rates of disease progression, and need for ART as well as increasing transmission risk. PMID:22089381

Changes in antiretroviral therapy guidelines: implications for public health policy and public purses.

PubMed

Hamilton, Alex; Garcia-Calleja, Jesus M; Vitoria, Marco; Gilks, Charles; Souteyrand, Yves; De Cock, Kevin; Crowley, Siobhan

2010-10-01

The World Health Organization (WHO) published a revision of the antiretroviral therapy (ART) guidelines and now recommends ART for all those with a CD4 cell count ≤350/mm(3), for people with HIV and active tuberculosis (TB) or chronic active hepatitis B irrespective of CD4 cell count and all HIV-positive pregnant women. A study was undertaken to estimate the impact of the new guidelines using four countries as examples. The current WHO/UNAIDS country projections were accessed based on the 2007 estimates for Zambia, Kenya, Cameroon and Vietnam. New projections were created using Spectrum. CD4 progression rates to need for ART were modified and compared with the baseline projections. The pattern of increased need for treatment is similar across the four projections. Initiating treatment at a CD4 count <250/mm(3) will increase the need for treatment by a median of 22% immediately, initiating ART at a CD4 count <350/mm(3) increases the need for treatment by a median of 60%, and the need for treatment doubles if ART is commenced at a CD4 count <500/mm(3). Initiating ART at a CD4 cell count <250/mm(3) would increase the need for treatment by a median of around 15% in 2012; initiating treatment at a CD4 count <350/mm(3) increases the need for treatment by a median of 42% across the same projections and about 84% if CD4 <500/mm(3) was used. The projections indicate that initiating ART earlier in the course of the disease by increasing the threshold for the initiation of ART would increase the numbers of adults in need of treatment immediately and in the future.

Anemia among HIV-Infected Patients Initiating Antiretroviral Therapy in South Africa: Improvement in Hemoglobin regardless of Degree of Immunosuppression and the Initiating ART Regimen.

PubMed

Takuva, Simbarashe; Maskew, Mhairi; Brennan, Alana T; Sanne, Ian; Macphail, A Patrick; Fox, Mathew P

2013-01-01

Among those with HIV, anemia is a strong risk factor for disease progression and death independent of CD4 count and viral load. Understanding the role of anemia in HIV treatment is critical to developing strategies to reduce morbidity and mortality. We conducted a prospective analysis among 10,259 HIV-infected adults initiating first-line ART between April 2004 and August 2009 in Johannesburg, South Africa. The prevalence of anemia at ART initiation was 25.8%. Mean hemoglobin increased independent of baseline CD4. Females, lower BMI, WHO stage III/IV, lower CD4 count, and zidovudine use were associated with increased risk of developing anemia during follow-up. After initiation of ART, hemoglobin improved, regardless of regimen type and the degree of immunosuppression. Between 0 and 6 months on ART, the magnitude of hemoglobin increase was linearly related to CD4 count. However, between 6 and 24 months on ART, hemoglobin levels showed a sustained overall increase, the magnitude of which was similar regardless of baseline CD4 level. This increase in hemoglobin was seen even among patients on zidovudine containing regimens. Since low hemoglobin is an established adverse prognostic marker, prompt identification of anemia may result in improved morbidity and mortality of patients initiating ART.

Trends in baseline CD4 cell counts and risk factors for late antiretroviral therapy initiation among HIV-positive patients in Shanghai, a retrospective cross-sectional study.

PubMed

Sun, Jianjun; Liu, Li; Shen, Jiayin; Chen, Panpan; Lu, Hongzhou

2017-04-19

There are few studies focus on the factors underlying the late initiation of ART in China. We analyzed the trends in the median CD4 cell counts among different patient groups over time and the risk factors for the late initiation of ART in Shanghai, China. A retrospective cross-sectional survey was made in the Department of Infectious Disease of Shanghai Public Health Clinical Center which is a designated diagnosis and treatment center for HIV-positive patients in Shanghai during the period of January 1st, 2008--June 30th, 2014. Late ART initiation was defined as a CD4 cell count <200 cells/mm 3 or having a clinical AIDS diagnosis prior to ART initiation. Trends in the median CD4 cell count at ART initiation and the proportion of late ART initiation by year were evaluated using Spearman's correlations and Chi-squared methods, respectively. We used a logistic regression model to analyze the risk factors for late ART initiation. The related factors collected in the multivariate model were the patient's age, gender, infection routes and marital status. A total of 3796 patients were analyzed in this study, with a median baseline CD4 cell count of 205 cells/mm 3 [interquartile range: 75-287]. The median CD4 cell counts of patients initiating ART late increased from 76 cells/mm 3 in 2008 to 103 cells/mm 3 in 2014 (p < 0.001), and the proportion of late ART initiation decreased from 80% to 45% (p < 0.001). The risk factors for late ART initiation were male gender, heterosexual transmission and older age (>30 years) (p < 0.001). Notable improvements were made in the median CD4 cell count at ART initiation and the proportion of late ART initiation from 2008 to 2014. However, persons with high risk of HIV exposure who are male, older even heterosexual orientation should be given more opportunities to receive frequently screening, earlier diagnoses and timely treatment.

Predictors of immunological failure of antiretroviral therapy among HIV infected patients in Ethiopia: a matched case-control study.

PubMed

Teshome, Wondu; Asefa, Anteneh; Assefa, Anteneh

2014-01-01

In resource constrained settings, immunological assessment through CD4 count is used to assess response to first line Highly Active Antiretroviral Therapy (HAART). In this study, we aim to investigate factors associated with immunological treatment failure. A matched case-control study design was used. Cases were subjects who already experienced immunological treatment failure and controls were those without immunological failure after an exactly or approximately equivalent duration of first line treatment with cases. Data were analyzed using SPSS v16.0. Conditional logistic regression was carried out. A total of 134 cases and 134 controls were included in the study. At baseline, the mean age ± 1 SD of cases was 37.5 ± 9.7 years whereas it was 36.9 ± 9.2 years among controls. The median baseline CD4 counts of cases and controls were 121.0 cells/µl (IQR: 47-183 cells/µl) and 122.0 cells/µl (IQR: 80.0-189.8 cells/µl), respectively. The median rate of CD4 cells increase was comparable for the two groups in the first six months of commencing HAART (P = 0.442). However, the median rate of CD4 increase was significantly different for the two groups in the next 6 months period (M6 to M12). The rate of increment was 8.8 (IQR: 0.5, 14.6) and 1.8 (IQR: 8.8, 11.3) cells/µl/month for controls and cases, respectively (Mann-Whitney U test, P = 0.003). In conditional logistic regressions grouped baseline CD4 count (P = 0.028), old age group and higher educational status (P<0.001) were significant predictors of immunological treatment failure. Subjects with immunological treatment failure have an optimal rate of immunological recovery in the first 6 months of treatment with first line HAART, but relative to the non-failing group the rate declines at a later period, notably between 6 and 12 months. Low baseline CD4 count, old age and higher educational status were associated with immunological treatment failure.

Late Antiretroviral Therapy (ART) Initiation Is Associated with Long-Term Persistence of Systemic Inflammation and Metabolic Abnormalities

PubMed Central

Ghislain, Mathilde; Bastard, Jean-Philippe; Meyer, Laurence; Capeau, Jacqueline; Fellahi, Soraya; Gérard, Laurence; May, Thierry; Simon, Anne; Vigouroux, Corinne; Goujard, Cécile

2015-01-01

Objectives HIV-induced immunodeficiency is associated with metabolic abnormalities and systemic inflammation. We investigated the effect of antiretroviral therapy (ART) on restoration of insulin sensitivity, markers of immune activation and inflammation. Methods Immunological, metabolic and inflammatory status was assessed at antiretroviral therapy initiation and three years later in 208 patients from the ANRS-COPANA cohort. Patients were compared according to their pre-ART CD4+ cell count (group 1: ≤ 200/mm3, n = 66 vs. group 2: > 200/mm3, n = 142). Results Median CD4+ cell count increased in both groups after 3 years of successful ART but remained significantly lower in group 1 than in group 2 (404 vs 572 cells/mm3). Triglyceride and insulin levels were higher or tended to be higher in group 1 than in group 2 at ART initiation (median: 1.32 vs 0.97 mmol/l, p = 0.04 and 7.6 vs 6.8 IU, p = 0.09, respectively) and remained higher after three years of ART (1.42 vs 1.16 mmol/L, p = 0.0009 and 8.9 vs 7.2 IU, p = 0.01). After adjustment for individual characteristics and antiretroviral therapy regimens (protease inhibitor (PI), zidovudine), insulin levels remained significantly higher in patients with low baseline CD4+ cell count. Baseline IL-6, sCD14 and sTNFR2 levels were higher in group 1 than in group 2. Most biomarkers of immune activation/inflammation declined during ART, but IL-6 and hsCRP levels remained higher in patients with low baseline CD4+ cell count than in the other patients (median are respectively 1.4 vs 1.1 pg/ml, p = 0.03 and 2.1 vs 1.3 mg/ml, p = 0.07). Conclusion After three years of successful ART, low pretreatment CD4+ T cell count remained associated with elevated insulin, triglyceride, IL-6 and hsCRP levels. These persistent metabolic and inflammatory abnormalities could contribute to an increased risk of cardiovascular and metabolic disease. PMID:26636578

Basal CD34+ Cell Count Predicts Peripheral Blood Stem Cell Mobilization in Healthy Donors after Administration of Granulocyte Colony-Stimulating Factor: A Longitudinal, Prospective, Observational, Single-Center, Cohort Study.

PubMed

Martino, Massimo; Gori, Mercedes; Pitino, Annalisa; Gentile, Massimo; Dattola, Antonia; Pontari, Antonella; Vigna, Ernesto; Moscato, Tiziana; Recchia, Anna Grazia; Barilla', Santina; Tripepi, Giovanni; Morabito, Fortunato

2017-07-01

A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 + cells on day 5 with emphasis on the predictive value of the basal CD34 + cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 + cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 + levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/µL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 + on day 5 using the baseline value of CD34 + as the key predictor was performed. On crude analysis, a baseline value of CD34 + ranging from .5 cells/µL to 1 cells/µL predicts a median value of 50 cells/µL on day 5; a value of 2 cells/µL predicts a median value of 70.7 cells/µL; a value of 3 cells/µL to 4 cells/µL predicts a median value of 91.3 cells/µL, and a value ≥ 5 predicts a median value of 112 cells/µL. In conclusion, the baseline PB CD34 + cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Effects of pharmacists' interventions on patient outcomes in an HIV primary care clinic.

PubMed

March, Kristi; Mak, May; Louie, Stan G

2007-12-15

The effects of pharmacists' interventions on patient outcomes in an HIV primary care clinic were studied. All study participants were referred to a pharmacist-managed drug optimization clinic (DOC) in a county-based HIV primary care clinic between November 1, 2003, and September 30, 2004. Patients were eligible for study participation if they were 18 years of age or older and gave informed consent to participate. Pharmacists' interventions were categorized as follows: patient education, addition of a medication, dosage adjustment, discontinuation of a medication, and interpretation of viral-resistance tests. Changes in baseline CD4+ T-lymphocyte counts and viral load were also measured over the study period. Toxicities related to highly active antiretroviral therapy were recorded and graded from 0 to 4, with 0 indicating no toxicity and 4 indicating severe toxicity. Study participants used a standardized survey to measure their own health-related quality of life. Changes in CD4+ lymphocyte counts and viral load were analyzed using Student's t test and analysis of variance. Toxicity grades were analyzed using the Wilcoxon signed-rank test. A total of 34 patients completed the study. Pharmacists made a total of 253 interventions, most of which were categorized as patient education. The mean CD4+ lymphocyte count increased from baseline levels by 54 +/- 78 cells/mm3 over the study period (p < 0.0002). The mean +/- S.D. reduction in circulating viral load over the study period was 1.02 log10 copies/mL ( p < 0.004). HIV-infected patients who were managed by pharmacists in a DOC demonstrated significant improvement from baseline in their CD4+ lymphocyte counts, viral loads, and drug-related toxicities.

Longitudinal effect of CD4 by cotrimoxazole use on malaria incidence among HIV-infected Ugandan adults on antiretroviral therapy: a randomized controlled study.

PubMed

Kasirye, Ronnie; Grosskurth, Heiner; Munderi, Paula; Levin, Jonathan; Anywaine, Zacchaeus; Nunn, Andrew; Kamali, Anatoli; Baisley, Kathy

2016-07-15

The effect of CD4 count on malaria incidence in HIV infected adults on antiretroviral therapy (ART) was assessed in the context of a randomized controlled trial on the effect of stopping cotrimoxazole (CTX). This study presents a sub-analysis of the COSTOP trial (ISRCTN44723643) which was carried out among HIV-infected Ugandan adults stable on ART with CD4 counts ≥250 cells/µl. Participants were randomized (1:1) to continue CTX or stop CTX and receive matching placebo, and were followed up for a minimum of 1 year (median 2.5 years). CD4 counts were measured at baseline, 3 months and then every 6 months. Clinical malaria was defined as fever and a positive blood slide. First, the relationship between current CD4 count during follow-up and malaria among participants on placebo was examined; using random effects Poisson regression to account for repeated episodes. Second, the effect of CD4 count at enrolment, CD4 count at ART initiation, and CD4 count during follow-up on malaria, was assessed within each trial arm; to examine whether the effect of CD4 count differed by CTX use. 2180 participants were enrolled into the COSTOP trial. The incidence of clinical malaria was approximately four episodes/100 person years in the CTX arm and 14 episodes/100 person years in the placebo arm. There was no evidence of an association of current CD4 and clinical malaria incidence (P = 0.56), or parasitaemia levels (P = 0.24), in the placebo arm. Malaria incidence did not differ by CD4 count at ART initiation, enrolment or during follow up, irrespective of CTX use. When compared with participants in the lowest CD4 stratum, rate ratios within each trial arm were all close to 1, and P values were all above P = 0.30. The immune status of HIV infected participants who are stable on ART as measured by CD4 count was not associated with malaria incidence and did not modify the effect of stopping CTX on malaria. The decision of whether to stop or continue CTX prophylaxis for malaria in HIV infected individuals who are stable on ART should not be based on CD4 counts alone. COSTOP trial registration number ISRCTN44723643.

Effects of incarceration on HIV-infected individuals.

PubMed

Griffin, M M; Ryan, J G; Briscoe, V S; Shadle, K M

1996-10-01

Human immunodeficiency virus (HIV) infection is a critical problem among the incarcerated population, with rates as high as 17% being reported for prison systems in New York. The literature suggests that stressful living conditions and inherent defects in the immune system associated with HIV infection make prison populations more susceptible to a disproportionate decrease in their CD4 counts. To determine the effects of incarceration on HIV-infected individuals, the charts of 800 inmates were reviewed. Baseline (draw 1), 2- to 5-month (draw 2), and 6- to 12-month (draw 3) CD4 cell counts were obtained. Mean cell counts were calculated, and paired t-tests were used to identify differences. The group receiving antiretrovirals throughout showed no difference in mean CD4 cell count between draws 1 and 2 or between draws 1 and 3. The group not receiving HIV medications did not show a significant difference in CD4 cell counts between draws 1 and 2, but did show a significant difference between draws 1 and 3. For this group, the rate of decline in CD4 cells was greater than among an outpatient setting. The subsample of subjects initiating therapy prior to the second blood draw showed a significant increase in mean CD4 cell counts at draw 1 versus draw 2, but did not show a significant change when comparing draw 1 to draw 3. When examining subjects based on their antiviral status, the mean CD4 cell count at each of the draws was statistically associated with subjects' antiviral status. We conclude that incarceration causes a more rapid decrease in CD4 cells compared with an outpatient population, causing clinical significance on the normal course of HIV disease.

Association of HIV transmission categories with sociodemographic, viroimmunological and clinical parameters of HIV-infected patients.

PubMed

Collazos, J; Asensi, V; Carton, J A

2010-07-01

To analyse sociodemographic, viroimmunological and clinical parameters in different HIV-transmission categories at baseline and during treatment, 3039 patients were followed up for 12 months after the initiation of a nelfinavir-based regimen. Multiple baseline parameters were significantly different in the diverse categories, including CD4 counts (P<0.0001) and viral load (P=0.02). There were differences in the groups regarding the CD4 response (P=0.01), but not the virological response (P=0.4), to therapy over time. Multivariate analyses revealed that transmission categories were significantly related to baseline CD4 counts (P=0.01), viral load at 12 months (P=0.0006), poorer adherence to therapy of injecting drug users (IDUs) vs. each of the other groups (P<0.001) and failure to complete the 12-month evaluation of IDU vs. heterosexual (P=0.003) and men who have sex with men (MSM) groups (P=0.02). We conclude that transmission categories had a significant influence on several baseline parameters and viroimmunological outcomes following highly active antiretroviral therapy (HAART), as well as on adherence to therapy and to medical appointments.

Immunogenicity and tolerability of yellow fever vaccination in 23 French HIV-infected patients.

PubMed

Pistone, Thierry; Verdière, Claire-Hélène; Receveur, Marie-Catherine; Ezzedine, Khaled; Lafon, Marie-Edith; Malvy, Denis

2010-09-01

Vaccination of asymptomatic human immunodeficiency virus (HIV)-infected patients with a CD4 cell count ≥ 200/mm³ is strongly suggested prior to travel to a region where yellow fever (YF) is endemic. However, few data describing YF vaccination in such patients are available. In this retrospective observational study of 23 HIV-infected patients, YF antibody titers, CD4 cell counts, and viral loads were measured before and after vaccination. Serologies were performed retrospectively on samples that had been stored as part of routine hospital procedures. Ninety-three percent of patients (13/14) with no baseline immunity, seroconverted after vaccination. Immunogenicity appeared slowly; only 2 of the 5 patients tested within 5 weeks of vaccination had seroconverted. A booster effect was noted in 3 of the 9 patients with baseline immunogenicity. Finally, due to unawareness of his HIV status, one patient was vaccinated and was found later to have a CD4 cell count < 200/mm³.The YF vaccine was well tolerated and no serious adverse events were reported. The impact of vaccination on immunologic and viral parameters was variable. Both decreases (n = 7) and increases (n = 5) in CD4 cell counts were recorded. Viral loads became undetectable in 2 patients and doubled or became positive in 3 patients. Yellow fever vaccination was safe and effective in a large majority of this cohort of stable, HIV-infected patients.

Prevalence and Persistence of Cervical Human Papillomavirus Infection In HIV-Positive Women Initiating Highly-Active Antiretroviral Therapy

PubMed Central

Fife, Kenneth H.; Wu, Julia W.; Squires, Kathleen E.; Watts, D. Heather; Andersen, Janet W.; Brown, Darron R.

2009-01-01

Objective To determine the prevalence of HPV DNA in cervical specimens from treatment-naïve women initiating highly active antiretroviral therapy (HAART) and explore the longitudinal association of HPV DNA with CD4 count and HIV viral load (VL). Methods Women enrolled prior to HAART were evaluated at baseline, weeks 24, 48, and 96 with CD4 count, VL, and cervical swab for HPV DNA. Results The 146 subjects had a median CD4 count of 238 cells/μL and VL of 13,894 copies/mL. Ninety-seven (66%) subjects had HPV DNA detected in the baseline specimen including 90 subjects (62%) positive for one or more high risk HPV types. HPV DNA detection declined to 49% at week 96, and that of a high risk HPV type to 39%. The duration of follow-up was associated with decreased detection of HPV DNA of any type (p=0.045) and of high risk HPV types (p=0.003). There was at most a marginal association between HAART response and loss of detection of cervical HPV DNA. Conclusions Women initiating HAART had a high prevalence of cervical HPV DNA that declined over 96 weeks of HAART. The relationship of CD4 count and VL response to the decline of cervical HPV DNA was not strong. PMID:19387354

Regulatory T Cells in Chronic Graft-Versus-Host Disease After Extracorporeal Photopheresis: Correlation With Skin and Global Organ Responses, and Ability to Taper Steroids.

PubMed

Denney, Helen A; Whittle, Robert J; Lai, Jennifer; Jacques, Richard M; Taylor, Peter C

2017-01-01

Induction of immune tolerance by an increase in regulatory T (Treg) cells after extracorporeal photopheresis (ECP) is thought to contribute to how ECP exerts its therapeutic effect in patients with chronic graft-versus-host disease (cGvHD). We investigated whether percentages and absolute counts of Treg cells changed post-ECP, and examined correlation with response. Absolute counts and % of CD4+ T cells and Treg cells (CD4 + CD25 + FOXP3 + CD127dim/-) were evaluated using flow cytometry in 32 patients with cGvHD treated by ECP for a minimum of 3 months, and up to 12 months. CD4+ or Treg cells at baseline to 12 months post-ECP were compared with changes in skin disease scores or global organ involvement, or the ability to taper steroids, at 14, 28, and 56 weeks. Regulatory T cells % increased significantly above any overall changes in CD4+ % at 6, 9, and 12 months post-ECP. There was no statistically significant association between Treg cells and skin or steroid response, whereas a larger increase in CD4+ count from baseline to 1 to 3 months corresponded to increased odds of being able to reduce steroid dose by 50% or greater at 14 weeks. Skin and global organ responders at 28 weeks had higher median Treg cell counts 3 months post-ECP than nonresponders, as did steroid responders at 56 weeks who were 12 months post-ECP. Regulatory T cell counts and % varied greatly among cGvHD patients, and the increase post-ECP was not significant until 6 months. No clear correlation was found between Treg cells and clinical improvement, suggesting that increases in Treg cell numbers and/or proportions are not driving the mechanism leading to a response after ECP.

[Assessment on depressive status and the therapeutic effects of highly active antiretroviral therapy among anti-HIV-1(+) population].

PubMed

Zhang, Li; Yang, Di; Zhao, Hong-xin; Han, Ning; Xiao, Jiang; Chen, Yu-fang; Han, Zhu; Li, Yan-mei; Wei, Kai; Zhang, Wen; Gao, Gui-ju

2013-05-01

To assess the depressive status and its influence on Chinese HIV-1(+) population, and how it was influenced by highly active antiretroviral therapy (HAART) and the CD4(+) T cell count. Anti-HIV-1(+) patients (age between 18 and 65 years old) who had met the criteria to commence the anti-HIV treatment but had not yet started, were selected from the Beijing Ditan Hospital between March 2011 and June 2012. BDI-II (Beck Depression Inventory) and a self-designed questionnaire were used to evaluate the baseline and the status of 48 weeks post the HAART treatment. Statistically, t test and the Wilcoxon rank sum test were used to compare the BDI scores under different conditions and before/after the HAART. (1) Of 100 subjects: male to female ratio was 99:1; the average age was 31.37 ± 5.58 years; the average education background was of 13.13 ± 3.51 years; the unemployed percentage was 4%; time before being identified as anti-HIV-1(+) was 5.0 (1.0 - 21.0) months; the percentage being infected through homosexual contact was 83%. The baseline BDI score was 6.0 (3 - 10.25). (2) There was no significant difference (P > 0.05) in BDI score between those subjects having had education less or more than 12 years; the BDI score of patients whose anti-HIV-1(+) was significantly higher (P < 0.05) among those discovered within the past 6 months than those more than 6 months. The BDI score of patients whose baseline CD4(+) T cell count below 200 cells/µl was significantly higher (P < 0.05) than those with baseline CD4(+) T cell count greater than 200 cells/µl. The CD4(+) T cell count was significantly high (P < 0.001) after 48 weeks of anti-viral treatment, but the BDI score was not significantly different (P > 0.05). There was no significant change (P > 0.05) in the proportion of patients with different degrees of BDI score before and after 48 weeks of antiviral treatment. Depression in HIV patients was most overt in the first six months when they were aware of the infection. The degree of depression was more severe in patients with baseline CD4(+) T cell count less than 200 cells/µl with improvement of immunity after the HAART did not alleviate the level of depression.

The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models

PubMed Central

Ford, Deborah; Robins, James M.; Petersen, Maya L.; Gibb, Diana M.; Gilks, Charles F.; Mugyenyi, Peter; Grosskurth, Heiner; Hakim, James; Katabira, Elly; Babiker, Abdel G.; Walker, A. Sarah

2015-01-01

In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organization stage 4 event (with CD4 count <250) was 0.96 (95% confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95% CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95% CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95% CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups by 48-week CD4 count, the mortality risk associated with CDM versus LCM was greater in persons with CD4 counts of <100 (hazard ratio = 2.4, 95% CI: 1.3, 4.3) than in those with CD4 counts of ≥100 (hazard ratio = 1.1, 95% CI: 0.8, 1.7; interaction P = 0.04). These findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks. PMID:26316598

The Relationship Between Caffeine Intake and Immunological and Virological Markers of HIV Disease Progression in Miami Adult Studies on HIV Cohort.

PubMed

Ramamoorthy, Venkataraghavan; Campa, Adriana; Rubens, Muni; Martinez, Sabrina S; Fleetwood, Christina; Stewart, Tiffanie; Liuzzi, Juan P; George, Florence; Khan, Hafiz; Li, Yinghui; Baum, Marianna K

2017-05-01

Although there are many studies on adverse health effects of substance use and HIV disease progression, similar studies about caffeine consumption are few. In this study, we investigated the effects of caffeine on immunological and virological markers of HIV disease progression. A convenience sample of 130 clinically stable people living with HIV/AIDS on antiretroviral therapy (65 consuming ≤250 mg/day and 65 consuming >250 mg/day of caffeine) were recruited from the Miami Adult Studies on HIV (MASH) cohort. This study included a baseline and 3-month follow-up visit. Demographics, body composition measures, substance use, Modified Caffeine Consumption Questionnaire (MCCQ), and CD4 count and HIV viral load were obtained for all participants. Multivariable linear regression and Linear Mixed Models (LMMs) were used to understand the effect of caffeine consumption on CD4 count and HIV viral load. The mean age of the cohort was 47.9 ± 6.4 years, 60.8% were men and 75.4% were African Americans. All participants were on ART during both the visits. Mean caffeine intake at baseline was 337.6 ± 305.0 mg/day and did not change significantly at the 3-month follow-up visit. Multivariable linear regressions after adjustment for covariates showed significant association between caffeine consumption and higher CD4 count (β = 1.532, p = 0.049) and lower HIV viral load (β = -1.067, p = 0.048). LMM after adjustment for covariates showed that the relationship between caffeine and CD4 count (β = 1.720, p = 0.042) and HIV viral load (β = -1.389, p = 0.033) continued over time in a dose-response manner. Higher caffeine consumption was associated with higher CD4 cell counts and lower HIV viral loads indicating beneficial effects on HIV disease progression. Further studies examining biochemical effects of caffeine on CD4 cell counts and viral replication need to be done in the future.

Antiretroviral Therapy for Prevention of Tuberculosis in Adults with HIV: A Systematic Review and Meta-Analysis

PubMed Central

Suthar, Amitabh B.; Lawn, Stephen D.; del Amo, Julia; Getahun, Haileyesus; Dye, Christopher; Sculier, Delphine; Sterling, Timothy R.; Chaisson, Richard E.; Williams, Brian G.; Harries, Anthony D.; Granich, Reuben M.

2012-01-01

Background Human immunodeficiency virus (HIV) infection is the strongest risk factor for developing tuberculosis and has fuelled its resurgence, especially in sub-Saharan Africa. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV worldwide. Antiretroviral therapy has substantial potential to prevent HIV-associated tuberculosis. We conducted a systematic review of studies that analysed the impact of antiretroviral therapy on the incidence of tuberculosis in adults with HIV infection. Methods and Findings PubMed, Embase, African Index Medicus, LILACS, and clinical trial registries were systematically searched. Randomised controlled trials, prospective cohort studies, and retrospective cohort studies were included if they compared tuberculosis incidence by antiretroviral therapy status in HIV-infected adults for a median of over 6 mo in developing countries. For the meta-analyses there were four categories based on CD4 counts at antiretroviral therapy initiation: (1) less than 200 cells/µl, (2) 200 to 350 cells/µl, (3) greater than 350 cells/µl, and (4) any CD4 count. Eleven studies met the inclusion criteria. Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis in all baseline CD4 count categories: (1) less than 200 cells/µl (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.07 to 0.36), (2) 200 to 350 cells/µl (HR 0.34, 95% CI 0.19 to 0.60), (3) greater than 350 cells/µl (HR 0.43, 95% CI 0.30 to 0.63), and (4) any CD4 count (HR 0.35, 95% CI 0.28 to 0.44). There was no evidence of hazard ratio modification with respect to baseline CD4 count category (p = 0.20). Conclusions Antiretroviral therapy is strongly associated with a reduction in the incidence of tuberculosis across all CD4 count strata. Earlier initiation of antiretroviral therapy may be a key component of global and national strategies to control the HIV-associated tuberculosis syndemic. Review Registration International Prospective Register of Systematic Reviews CRD42011001209 Please see later in the article for the Editors' Summary. PMID:22911011

Fatigue in HIV illness: relationship to depression, physical limitations, and disability.

PubMed

Ferrando, S; Evans, S; Goggin, K; Sewell, M; Fishman, B; Rabkin, J

1998-01-01

This study was conducted to investigate the prevalence of clinical fatigue reported by gay/bisexual men at all HIV illness stages, and whether fatigue, while associated with depression, independently contributes to limitations in physical function and disability. HIV- men, HIV+ men with CD4 counts >500, HIV+ men with CD4 counts 200 to 500, and men with AIDS were compared on prevalence of clinical fatigue, as defined by a standardized instrument. Among HIV+ men, the relationships among fatigue, depressed mood, major depressive disorder, HIV illness markers (including CD4 count and HIV RNA viral load), physical limitations, and disability were assessed at baseline and after 1 year. The prevalence of clinical fatigue in men with CD4 counts <500 was 14%, significantly higher than HIV- men and HIV+ men with CD4 counts >500. However, fatigue was not directly correlated with CD4 count or HIV RNA. Fatigue was a chronic symptom that was associated with depressed mood, major depressive disorder, physical limitations, and disability. After 1 year, an increase in depressive symptoms predicted a small amount of variance in fatigue; however, depressive symptoms were not associated with physical limitations or disability after controlling for fatigue. Fatigue is a chronic symptom that is more prevalent in advanced HIV illness, and which, although associated with depression, does not seem to be merely a symptom of depression. Because fatigue contributes independently to physical limitations and disability, it should be assessed and treated.

Impact of exposure to intimate partner violence on CD4+ and CD8+ T cell decay in HIV infected women: longitudinal study.

PubMed

Jewkes, Rachel; Dunkle, Kristin; Jama-Shai, Nwabisa; Gray, Glenda

2015-01-01

Intimate partner violence (IPV) is a risk factor for HIV acquisition in many settings, but little is known about its impact on cellular immunity especially in HIV infected women, and if any impact differs according to the form of IPV. We tested hypotheses that exposure to IPV, non-partner rape, hunger, pregnancy, depression and substance abuse predicted change in CD4+ and CD8+ T-cell count in a dataset of 103 HIV infected young women aged 15-26 enrolled in a cluster randomised controlled trial. Multiple regression models were fitted to measure rate of change in CD4 and CD8 and including terms for age, person years of CD4+/CD8+ T-cell observation, HIV positivity at baseline, and stratum. Exposure variables included drug use, emotional, physical or sexual IPV exposure, non-partner rape, pregnancy and food insecurity. Mean CD4+ T cell count at baseline (or first HIV+ test) was 567.6 (range 1121-114). Participants were followed for an average of 1.3 years. The magnitude of change in CD4 T-cells was significantly associated with having ever experienced emotional abuse from a current partner at baseline or first HIV+ test (Coeff -132.9 95% CI -196.4, -69.4 p<0.0001) and drug use (Coeff -129.9 95% CI -238.7, -21.2 p=0.02). It was not associated with other measures. The change in CD8 T-cells was associated with having ever experienced emotional abuse at baseline or prior to the first HIV+ test (Coeff -178.4 95%CI -330.2, -26.5 p=0.02). In young ART-naive HIV positive women gender-based violence exposure in the form of emotional abuse is associated with a faster rate of decline in markers of cellular immunity. This highlights the importance of attending to emotional abuse when studying the physiological impact of IPV experience and the mechanisms of its impact on women's health.

Loss to Follow-Up in a Community Clinic in South Africa – Roles of Gender, Pregnancy and CD4 count

PubMed Central

Wang, Bingxia; Losina, Elena; Stark, Ruth; Munro, Alison; Walensky, Rochelle P.; Wilke, Marisa; Martin, Des; Lu, Zhigang; Freedberg, Kenneth A.; Wood, Robin

2013-01-01

Background Faith-based organizations have expanded access to antiretroviral therapy (ART) in community clinics across South Africa. Loss to follow-up (LTFU), however, limits both the potential individual and population treatment benefits and is an obstacle to optimal care. Objective To identify patient characteristics associated with LTFU six months after starting ART in patients in a large South African community clinic. Methods Patients initiating ART between April 2004 and October 2006 in one Catholic Relief Services HIV treatment clinic who had at least one follow-up visit were included in the analysis. Standardized instruments were used for data collection. Routine monitoring was performed every 6 months following ART initiation. Rates of LTFU over time were estimated by the Kaplan-Meier method. The log-rank test was used to examine the impact of age, baseline CD4 count, HIV RNA, gender and pregnancy status for women on LTFU. Cox proportional hazard regression was performed to analyze hazard ratios for LTFU. Results Data from 925 patients (age > 14 years), median age 36 years, 70% female (16% pregnant) were included in the analysis. Fifty one patients (6%) were lost to follow-up six months after ART initiation. When stratified by baseline CD4 count, gender and pregnancy status, pregnant women with lower baseline CD4 count (≤200 /μl) had 6.06 times (95% CI: 2.20 – 16.71) the hazard of LTFU compared to men. Conclusions HIV-infected pregnant women initiating ART are significantly more likely to be lost to follow-up in a community clinic in South Africa. Interventions to successfully retain pregnant women in care are urgently needed. PMID:21786730

When to Initiate Combined Antiretroviral Therapy to Reduce Mortality and AIDS-Defining Illness in HIV-Infected Persons in Developed Countries

PubMed Central

2012-01-01

Background Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 109 cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. Objective To identify the optimal CD4 cell count at which cART should be initiated. Design Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 109 cells/L. Setting HIV clinics in Europe and the Veterans Health Administration system in the United States. Patients 20 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 109 cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 109 cells/L and were included in the analysis. Measurements Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Results Compared with initiating cART at the CD4 cell count threshold of 0.500 × 109 cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. Limitations CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Conclusion Initiation of cART at a threshold CD4 count of 0.500 × 109 cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 ×109 cells/L. Primary Funding Source National Institutes of Health. PMID:21502648

When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries: an observational study.

PubMed

Cain, Lauren E; Logan, Roger; Robins, James M; Sterne, Jonathan A C; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C; von Wyl, Viktor; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Remonie; Meyer, Laurence; Perez-Hoyos, Santiago; Muga, Roberto; Lodi, Sara; Lanoy, Emilie; Costagliola, Dominique; Hernan, Miguel A

2011-04-19

Most clinical guidelines recommend that AIDS-free, HIV-infected persons with CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy (cART), but the optimal CD4 cell count at which cART should be initiated remains a matter of debate. To identify the optimal CD4 cell count at which cART should be initiated. Prospective observational data from the HIV-CAUSAL Collaboration and dynamic marginal structural models were used to compare cART initiation strategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L. HIV clinics in Europe and the Veterans Health Administration system in the United States. 20, 971 HIV-infected, therapy-naive persons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and no previous AIDS-defining illnesses, of whom 8392 had a CD4 cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L and were included in the analysis. Hazard ratios and survival proportions for all-cause mortality and a combined end point of AIDS-defining illness or death. Compared with initiating cART at the CD4 cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was 1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48) for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to 1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combined end point of AIDS-defining illness or death. CD4 cell count at cART initiation was not randomized. Residual confounding may exist. Initiation of cART at a threshold CD4 count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortality did not vary substantially with the use of CD4 thresholds between 0.300 and 0.500 × 10(9) cells/L.

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania

PubMed Central

Kawai, Kosuke; Villamor, Eduardo; Mugusi, Ferdinand M; Saathoff, Elmar; Urassa, Willy; Bosch, Ronald J; Spiegelman, Donna; Fawzi, Wafaie W

2012-01-01

BACKGROUND Patients with tuberculosis (TB) often suffer from profound malnutrition. OBJECTIVE To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. METHODS A total of 471 HIV-positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months TB treatment following enrollment. RESULTS About 40% of HIV-positive and 47% of HIV-negative TB patients had BMI <18.5 kg/m2 at baseline. About 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV-positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Female sex, older age, low CD4 cell counts, previous TB infection, and less money spent on food were independently associated with a smaller improvement in hemoglobin among HIV-positive patients during treatment. CONCLUSION HIV- positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment. PMID:22283899

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania.

PubMed

Kawai, K; Villamor, E; Mugusi, F M; Saathoff, E; Urassa, W; Bosch, R J; Spiegelman, D; Fawzi, W W

2011-10-01

Patients with tuberculosis (TB) often suffer from profound malnutrition. To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. A total of 471 human immunodeficiency virus (HIV) positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months' TB treatment following enrollment. About 40% of HIV-positive and 47% of HIV-negative TB patients had body mass index (BMI) < 18.5 kg/m 2 at baseline, while about 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV- positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Fe- male sex, older age, low CD4 cell counts, previous TB infection and less money spent on food were independently associated with a smaller improvement in hemoglobin levels among HIV-positive patients during treatment. HIV-positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment.

Efficacy of Cyto-Chex blood preservative for delayed manual CD4 testing using Dynal T4 Quant CD4 test among HIV-infected persons in Zambia.

PubMed

Truett, April A; Letizia, Andrew; Malyangu, Evans; Sinyangwe, Frank; Morales, Brandi N; Crum, Nancy F; Crowe, Suzanne M

2006-02-01

Manual CD4 tests such as Dynal T4 Quant (Dynabeads, Dynal Biotech, Oslo, Norway) are less expensive alternatives to flow cytometry in resource-limited countries. Whereas blood preservatives have proven useful for stabilizing blood samples to allow delayed CD4 testing by flow cytometry, they have not been verified for manual tests. A method for preservation of blood prior to manual CD4 testing is needed for long-distance transport or sample batching. Blood from HIV-positive Zambian military beneficiaries was mixed (1:1) with Cyto-Chex (Streck Laboratories, La Vista, NE) blood preservative, and the blood was stored at refrigerated, ambient, and incubator (37 degrees C) temperatures prior to Dynabeads CD4 testing at 0, 3, 6, and 9 days after collection. Baseline flow cytometry and Dynabeads testing without preservative were performed for comparison. Twenty-seven patient samples were analyzed. Dynabeads vs. flow cytometry had a correlation coefficient (r) of 0.84. There was excellent correlation (r = 0.96) between baseline Dynabeads testing and Cyto-Chex-preserved samples. Refrigerated samples showed strong correlation with baseline Dynabeads (r = 0.93-0.95) on days 3, 6, and 9 without decline in CD4 count (P = 0.73). Samples stored at ambient temperature yielded inferior results (r = 0.76-0.81), with a significant decline in CD4 count by day 3 (P < 0.001). The incubator arm had especially poor correlation (r = 0.30-0.49). Addition of Cyto-Chex to peripheral blood (1:1) adequately preserves refrigerated blood samples for up to 9 days for subsequent testing with Dynabeads CD4 test. Cyto-Chex, however, cannot be recommended for delayed Dynabeads CD4 testing with storage at 37 degrees C or ambient temperatures in tropical areas similar to the site of this study.

Are persons living with HIV timely accessing ART services in India?

PubMed

Sogarwal, Ruchi; Bachani, Damodar

2009-05-01

CD4+ T-cell level is one of the important criteria for categorising HIV-related clinical conditions to determine initiation of antiretroviral therapy (ART). The present study is undertaken to analyse baseline CD4 count at which persons living with HIV/AIDS (PLHA) were getting registered for ART in India. It also examines the profile of the PLHA with baseline CD4 count over a period of time. Data of 1,10,974 registered PLHAs at ART centres were analysed for the last three years (April 2005 to March 2008) in the computerised management information system. It was revealed that 85 per cent of PLHA were registered when their baseline CD4 count was less than 250 cells/mm3 and thus were eligible for initiation of ART. No significant change in the proportion of PLHA by CD4 categories was observed in the last three years. These findings suggest that registration for ART at early stages of infection is still uncommon. Significant decline in the proportion of PLHA in the age group of 21-30 years, literate and employed was noticed. The proportion of PLHA referred by counselling and testing centres has increased from 62.6% in 2005-06 to 71.3% in 2007-08. Sexual transmission, followed by mother to child transmission has been reported as two major modes of HIV transmission by PLHA registered at ART centres in the last three years. Though the number of ART centres has increased in India which in turn has increased the number of PLHAs registered and on ART, it is evident from this study that the programme is still far behind to achieve the goal of early detection for timely ART.

Improved neurocognitive test performance in both arms of the SMART study: impact of practice effect

PubMed Central

Grund, Birgit; Wright, Edwina J.; Brew, Bruce J.; Price, Richard W.; Roediger, Mollie P.; Bain, Margaret P.; Hoy, Jennifer F.; Shlay, Judith C.; Vjecha, Michael J.; Robertson, Kevin R.

2013-01-01

We evaluated factors associated with improvement in neurocognitive performance in 258 HIV-infected adults with baseline CD4 lymphocyte counts above 350 cells/mm3 randomized to intermittent, CD4-guided antiretroviral therapy (ART) (128 participants) versus continuous therapy (130) in the Neurology substudy of the Strategies for Management of Antiretroviral Therapy trial. Participants were enrolled in Australia, North America, Brazil, and Thailand, and neurocognitive performance was assessed by a five-test battery at baseline and month 6. The primary outcome was change in the quantitative neurocognitive performance z score (QNPZ-5), the average of the z scores of the five tests. Associations of the 6-month change in test scores with ART use, CD4 cell counts, HIV RNA levels, and other factors were determined using multiple regression models. At baseline, median age was 40 years, median CD4 cell count was 513 cells/mm3, 88 % had plasma HIV RNA ≤400 copies/mL, and mean QNPZ-5 was −0.68. Neurocognitive performance improved in both treatment groups by 6 months; QNPZ-5 scores increased by 0.20 and 0.13 in the intermittent and continuous ART groups, respectively (both P<0.001 for increase and P=0.26 for difference). ART was used on average for 3.6 and 5.9 out of the 6 months in the intermittent and continuous ART groups, respectively, but the increase in neurocognitive test scores could not be explained by ART use, changes in CD4, or plasma HIV RNA, which suggests a practice effect. The impact of a practice effect after 6 months emphasizes the need for a control group in HIV studies that measure intervention effects using neurocognitive tests similar to ours. PMID:23943468

Opportunistic Infections and Complications in Human Immunodeficiency Virus-1-Infected Children

PubMed Central

Yadav, Jaivinder; Nanda, Sanjeev; Sharma, Deepak

2014-01-01

Objectives: The aim of this study was to ascertain the correlation between various opportunistic infections and complications in human immunodeficiency virus (HIV)-1-infected children and the immune status of these patients, evaluated by absolute cluster of differentiation 4 (CD4) count and CD4 percentage. Methods: This study was conducted from January 2009 to June 2010 at the Antiretroviral Treatment Centre of the Pt. B.D. Sharma Post Graduate Institute of Medical Sciences, a tertiary care hospital in Rohtak, Haryana, in northern India. A total of 20 HIV-1-infected children aged 4–57 months were studied. Demographic and baseline investigations were performed prior to the start of highly active antiretroviral therapy (HAART). A fixed-dose combination of HAART was given based on the patient’s weight. Baseline investigations were repeated after six months of HAART. Results: There was a significant increase in the patients’ haemoglobin, weight, height and CD4 count after six months of HAART. Significant improvements (P <0.05) were also noted in the patients’ immune status, graded according to the World Health Organization. Conclusion: This study observed that the severity and frequency of opportunistic complications in paediatric patients with HIV-1 increased with a fall in the CD4 count. The treatment of opportunistic infections, along with antiretroviral therapy, may lead to both clinical and immunological recovery as well as a decreased incidence of future opportunistic infections. The CD4 count may give treating physicians an initial idea about the immune status of each child and could also be used as a biological marker of HAART efficacy. Patient compliance must be ensured during HAART as this is a key factor in improving outcomes. PMID:25364555

A Bereavement Support Group Intervention Is Longitudinally Associated with Salutary Effects on the CD4 Cell Count and Number of Physician Visits

PubMed Central

Goodkin, Karl; Feaster, Daniel J.; Asthana, Deshratn; Blaney, Nancy T.; Kumar, Mahendra; Baldewicz, Teri; Tuttle, Raymond S.; Maher, Kevin J.; Baum, Marianna K.; Shapshak, Paul; Fletcher, Mary Ann

1998-01-01

A randomized, controlled, clinical trial was conducted to examine the impact of a semistructured, 10-week, once weekly, 90-min/session bereavement support group intervention on immunological, neuroendocrine, and clinical health status in human immunodeficiency virus type 1-seropositive (HIV-1+) and HIV-1-seronegative (HIV-1−) homosexual men, compared to a standard of care control condition. A total of 119 homosexual men (74 HIV-1+ and 45 HIV-1−) were assessed at baseline, 10 weeks, and 6 months follow-up. At the 6-month follow-up assessment, the intervention groups exhibited significant beneficial effects compared to controls on changes in CD4 cell, total T-lymphocyte, and total lymphocyte counts, when baseline levels, antiretroviral medication use, CDC stage of disease, and other potentially confounding factors were accounted for. There was no statistically significant effect on the CD4/CD8 ratio or on the CD8 cell count. The effect on CD4 cell count was associated with group attendance and with changes in plasma cortisol level. Plasma cortisol levels decreased significantly among intervention subjects, compared to controls. A significantly reduced number of health care visits over the 6-month follow-up period among the intervention subjects supported the clinical relevance of the immunological changes observed for both HIV-1+ and HIV-1− individuals. These results indicate that behavioral interventions may have salutary immunological and clinical health effects following bereavement among HIV-1-infected individuals. The effect in HIV-1− individuals suggests that this bereavement support group intervention might have similar salutary effects in the general population. Potential effects of such interventions on clinical HIV disease progression are of interest and should be studied. PMID:9605995

Strongyloidiasis Epidemiology and Treatment Response in Patients with HIV Infection

PubMed Central

Cortes-Penfield, Nicolas; Moore, Cody; Arduino, Roberto; Serpa, Jose

2017-01-01

Abstract Background We sought to characterize the epidemiology of HIV and S. stercoralis coinfection in an urban HIV cohort, and to investigate the effect of S. stercoralis infection on HIV virologic control and immune recovery. Methods We reviewed the medical records of all HIV-infected patients diagnosed with strongyloidiasis who received care at Thomas Street Health Center (Houston, TX) between 2000 and 2015. For each case we included up to two matched HIV-infected patients without strongyloidiasis (controls). Matching was based on age, sex, ethnicity, baseline CD4 percentage, and HIV viral load at the time of strongyloidiasis diagnosis in the case patient. We recorded patient demographics, comorbidities, CD4 count and percentage, HIV viral load, and absolute eosinophilia count (AEC) at the time of HIV diagnosis, strongyloidiasis diagnosis, and six and twelve months after ivermectin treatment. Results We identified 15 cases of HIV and S.stercoralis coinfection; 13 had at least one available matched control. The mean age of coinfected patients was 45; all were Hispanic, 84.6% were male, and the mean CD4 nadir was 146 cells/ul. At the time of strongyloidiasis diagnosis, the mean CD4 count was 460 cells/ul, HIV RNA viral load 2.07 logs/ml, and AEC was 1,360 cells/μL. At 6 and 12 months after treatment, CD4 counts were 514 and 464 cells/μL, HIV RNA viral loads 1.78 and 2.31 log/mL, and AECs 319 and 362 cells/μL, respectively. Although CD4 counts increased 6 months after treatment, they returned to baseline levels at 12 months; neither change achieved statistical significance. The reduction in AECs after ivermectin treatment was statistically significant (P < 0.001). Matched controls without S.stercoralis had lower AECs at baseline, 6 months, and 12 months; otherwise, there were no differences between cases and controls. Conclusion Strongyloidiasis treatment in HIV-infected patients led to normalization of the AEC at 6 months in most cases, but AECs remained higher than in control patients. Persistently elevated AECs may suggest treatment failure or reinfection. Our study was unable to identify any effect of S. stercoralis infection or treatment on HIV virologic suppression or immunologic recovery; larger studies are warranted to investigate the effect of strongyloidiasis on HIV disease. Disclosures All authors: No reported disclosures.

Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial.

PubMed

Fogel, Jessica M; Hudelson, Sarah E; Ou, San-San; Hart, Stephen; Wallis, Carole; Morgado, Mariza G; Saravanan, Shanmugam; Tripathy, Srikanth; Hovind, Laura; Piwowar-Manning, Estelle; Sabin, Devin; McCauley, Marybeth; Gamble, Theresa; Zhang, Xinyi C; Eron, Joseph J; Gallant, Joel E; Kumwenda, Johnstone; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James; Badal-Faesen, Sharlaa; Akelo, Victor; Hosseinipour, Mina C; Santos, Breno R; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H

2016-07-01

Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts.

Robust interferon-α and IL-12 responses by dendritic cells are related to efficient CD4+ T-cell recovery in HIV patients on ART.

PubMed

Tan, Dino Bee Aik; Yong, Yean Kong; Lim, Andrew; Tan, Hong Yien; Kamarulzaman, Adeeba; French, Martyn; Price, Patricia

2011-05-01

Amongst HIV patients with successful virological responses to antiretroviral therapy (ART), poor CD4(+) T-cell recovery is associated with low nadir CD4(+) T-cell counts and persistent immune activation. These factors might be influenced by dendritic cell (DC) function. Interferon-α-producing plasmacytoid DC and IL-12-producing myeloid DC were quantified by flow cytometry after stimulation with agonists to TLR7/8 (CL075) or TLR9 (CpG-ODN). These were compared between patients who achieved CD4(+) T-cell counts above or below 200 cells/μL after 6 months on ART (High vs. Low groups). High Group patients had more DC producing interferon-α or IL-12 at Weeks 6 and 12 on ART than Low Group patients. The frequencies of cytokine-producing DC at Week 12 were directly correlated with CD4(+) T-cell counts at baseline and at Week 12. Patients with good recovery of CD4(+) T-cells had robust TLR-mediated interferon-α responses by plasmacytoid DC and IL-12 responses by myeloid DC during early ART (1-3 months). Copyright © 2011 Elsevier Inc. All rights reserved.

Short-term additional enfuvirtide therapy is associated with a greater immunological recovery in HIV very late presenters: a controlled pilot study.

PubMed

Bonora, S; Calcagno, A; Cometto, C; Fontana, S; Aguilar, D; D'Avolio, A; Gonzalez de Requena, D; Maiello, A; Dal Conte, I; Lucchini, A; Di Perri, G

2012-02-01

To evaluate whether the addition of enfuvirtide to standard highly active antiretroviral therapy (HAART) could confer immunovirological benefits in human immunodeficiency virus (HIV)-infected very late presenters. The current study is an open comparative therapeutic trial of standard protease inhibitor (PI)-based HAART ± additional enfuvirtide in treatment-naïve deeply immunologically impaired HIV-positive patients. Very late presenters (CD4 <50/mm(3)), without tuberculosis and neoplasms, were alternatively allocated to two nucleoside reverse transcriptase inhibitors (NRTIs) and lopinavir/ritonavir without (control arm, CO) or with (ENF arm) enfuvirtide 90 mg bid. Enfuvirtide was administered until the achievement of viral load <50 copies/ml and for at least 24 weeks. The primary objective was the magnitude of CD4+ cell recovery at 6 months. HIV RNA was intensively monitored in the first month, and, thereafter, monthly, as for CD4+ cell count and percentage, clinical data, and plasma drug concentrations. Of 22 enrolled patients (11 per arm), 19 completed the study (10 in the ENF arm). Baseline CD4+ cell counts and % were comparable, with 20 CD4+/mm(3) (12-37) and a percentage of 3.3 (1.7-7.1) in the ENF arm, and 16 CD4+/mm(3) (9-29) and a percentage of 3.1 (2.3-3.8) in the CO arm, respectively. The baseline viral load was also comparable between the two arms, with 5.77 log10 (5.42-6) and 5.39 log10 (5.06-6) in the ENF and CO arms, respectively. Enfuvirtide recipients had higher CD4+ percentage at week 8 (7.6 vs. 3.6%, p = 0.02) and at week 24 (10.7 vs. 5.9%, p = 0.02), and a greater CD4+ increase at week 24 (207 vs. 134 cells/mm(3), p = 0.04), with 70% of enfuvirtide intakers versus 12.5% of controls who achieved a CD4+ cell count >200/mm(3) (p = 0.01). At 48 weeks, patients in the ENF arm had CD4+ cell counts higher than controls (251 vs. 153cells/mm(3), p = 0.04) and were also found to be faster in reaching a CD4 cell count over 200/mm(3): 18 (8-24) versus 48 (36-108) weeks (p = 0.01). Viral load decay at week 4 was greater in the ENF arm (-3 vs. -2.2 log, p = 0.04), while the proportion of patients with viral load <50 copies/ml at week 24 was comparable. In this pilot study, the addition of enfuvirtide to a lopinavir-based HAART was shown to be associated with a significantly faster and greater immunological recovery in newly discovered HIV-positive patients with very low CD4+ cell counts. Induction strategies using an enfuvirtide-based approach in such subjects warrant further investigation.

Mindfulness meditation training effects on CD4+ T lymphocytes in HIV-1 infected adults: A small randomized controlled trial

PubMed Central

Creswell, J. David; Myers, Hector F.; Cole, Steven W.; Irwin, Michael R.

2009-01-01

Mindfulness meditation training has stress reduction benefits in various patient populations, but its effects on biological markers of HIV-1 progression are unknown. The present study tested the efficacy of an 8-week Mindfulness-based stress reduction (MBSR) meditation program compared to a 1-day control seminar on CD4+ T lymphocyte counts in stressed HIV infected adults. A single-blind randomized controlled trial was conducted with enrollment and follow-up occurring between November 2005 and December 2007. A diverse community sample of 48 HIV-1 infected adults was randomized and entered treatment in either an 8-week MBSR or a 1-day control stress reduction education seminar. The primary outcome was circulating counts of CD4+ T lymphocytes. Participants in the 1-day control seminar showed declines in CD4+ T lymphocyte counts whereas counts among participants in the 8-week MBSR program were unchanged from baseline to post-intervention (time × treatment condition interaction, p = .02). This effect was independent of antiretroviral (ARV) medication use. Additional analyses indicated that treatment adherence to the mindfulness meditation program, as measured by class attendance, mediated the effects of mindfulness meditation training on buffering CD4+ T lymphocyte declines. These findings provide an initial indication that mindfulness meditation training can buffer CD4+ T lymphocyte declines in HIV-1 infected adults. PMID:18678242

Cytomegalovirus retinitis in acquired immunodeficiency syndrome patients: A problem worth giving attention to.

PubMed

Gupta, Priti Kapadia; Patel, Nikunj V; Patel, Shivani D; Patel, Kunjan J

2014-01-01

Cytomegalovirus (CMV) retinitis remains the most common ocular opportunistic infection in patients with acquired immunodeficiency syndrome even in the era of highly active antiretroviral therapy (HAART). Increased survival of patients on HAART has increased incidence of blindness, which will further increase in the future. The objective of this study was to determine the incidence of CMV retinitis and the effect of HAART on the natural history of CMV retinitis in patients referred from ART center. Patients with baseline/current CD4 counts <150 cells/µl were evaluated for CMV retinitis. Complete ophthalmological evaluation was carried out and records of CD4 counts, HAART regime, presence of any form of CMV retinitis and response to HAART were noted. Out of 800 patients registered with CD4 <150 cells/µl in ART center, 100 patients reached us. Among these, CMV retinitis was observed in 15% patients, with median CD4 count at the time of examination being 56 cells/µl (range: 24-306 cells/µl). 66.67% patients were HAART non-responders and 63.6% eyes were economically blind. CMV retinitis occurs even in patients with higher CD4 counts. Timely diagnosis and intervention of this treatable condition can reduce the number of blinding years in these young patients who otherwise live longer as a result of HAART.

Incidence and risk factors of antiretroviral treatment failure in treatment-naïve HIV-infected patients at Chiang Mai University Hospital, Thailand

PubMed Central

2011-01-01

Background The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients. Methods A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand. Results From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001). Conclusions This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART. PMID:22060823

Joint longitudinal data analysis in detecting determinants of CD4 cell count change and adherence to highly active antiretroviral therapy at Felege Hiwot Teaching and Specialized Hospital, North-west Ethiopia (Amhara Region).

PubMed

Seyoum, Awoke; Ndlovu, Principal; Temesgen, Zewotir

2017-03-16

Adherence and CD4 cell count change measure the progression of the disease in HIV patients after the commencement of HAART. Lack of information about associated factors on adherence to HAART and CD4 cell count reduction is a challenge for the improvement of cells in HIV positive adults. The main objective of adopting joint modeling was to compare separate and joint models of longitudinal repeated measures in identifying long-term predictors of the two longitudinal outcomes: CD4 cell count and adherence to HAART. A longitudinal retrospective cohort study was conducted to examine the joint predictors of CD4 cell count change and adherence to HAART among HIV adult patients enrolled in the first 10 months of the year 2008 and followed-up to June 2012. Joint model was employed to determine joint predictors of two longitudinal response variables over time. Furthermore, the generalized linear mixed effect model had been used for specification of the marginal distribution, conditional to correlated random effect. A total of 792 adult HIV patients were studied to analyze the longitudinal joint model study. The result from this investigation revealed that age, weight, baseline CD4 cell count, ownership of cell phone, visiting times, marital status, residence area and level of disclosure of the disease to family members had significantly affected both outcomes. From the two-way interactions, time * owner of cell phone, time * sex, age * sex, age * level of education as well as time * level of education were significant for CD4 cell count change in the longitudinal data analysis. The multivariate joint model with linear predictor indicates that CD4 cell count change was positively correlated (p ≤ 0.0001) with adherence to HAART. Hence, as adherence to HAART increased, CD4 cell count also increased; and those patients who had significant CD4 cell count change at each visiting time had been encouraged to be good adherents. Joint model analysis was more parsimonious as compared to separate analysis, as it reduces type I error and subject-specific analysis improved its model fit. The joint model operates multivariate analysis simultaneously; and it has great power in parameter estimation. Developing joint model helps validate the observed correlation between the outcomes that have emerged from the association of intercepts. There should be a special attention and intervention for HIV positive adults, especially for those who had poor adherence and with low CD4 cell count change. The intervention may be important for pre-treatment counseling and awareness creation. The study also identified a group of patients who were with maximum risk of CD4 cell count change. It is suggested that this group of patients needs high intervention for counseling.

High CMV IgG antibody levels are associated to a lower CD4+ RESPONSE to antiretroviral therapy in HIV-infected women.

PubMed

Giuliano, Marina; Pirillo, Maria Franca; Liotta, Giuseppe; Andreotti, Mauro; Jere, Haswell; Sagno, Jean-Baptiste; Ciccacci, Fausto; Amici, Roberta; Marazzi, Maria Cristina; Vella, Stefano; Palombi, Leonardo; Mancinelli, Sandro

2017-11-01

Virtually all HIV-infected women in sub-Saharan Africa have evidence of Cytomegalovirus (CMV) infection and levels of specific anti-CMV IgG have been suggested to represent more intense reactivation of subclinical infection. Studies have also shown direct influence of CMV on lymphocytes. The aim of this study was to determine if levels of anti-CMV specific antibodies could impact on the immunological response to antiretroviral treatment (ART) in HIV-infected pregnant women. CMV-specific IgG were measured in HIV-infected pregnant women at 26 weeks of gestation (before ART initiation). Women received ART until 6 months postpartum or indefinitely according to local guidelines at the time of the study. Immunological and virological responses were assessed 6 months and 24 months after delivery. A total of 81 women were studied. At baseline high levels (above the median) of specific IgG were associated to a low CD4+ cell count (P<0.001), a high viral load (P=0.003), and to an older age (P=0.051). In a multivariate model adjusting for baseline CD4+ count, baseline viral load and age, the presence of low levels of CMV IgG was the only independent predictor of a a CD4+ count above 500/mm 3 24 months after delivery among women on continuous therapy. In this cohort, levels of CVM IgG had a significant influence on the immunological response to ART, adding information to the known impact of CMV infection in the HIV-positive population, and underlining the need of new strategies to contain the infection. Copyright © 2017 Elsevier B.V. All rights reserved.

CD4-dependent characteristics of coreceptor use and HIV type 1 V3 sequence in a large population of therapy-naive individuals.

PubMed

Low, Andrew J; Marchant, David; Brumme, Chanson J; Brumme, Zabrina L; Dong, Winnie; Sing, Tobias; Hogg, Robert S; Montaner, Julio S G; Gill, Vikram; Cheung, Peter K; Harrigan, P Richard

2008-02-01

We investigated the associations between coreceptor use, V3 loop sequence, and CD4 count in a cross-sectional analysis of a large cohort of chronically HIV-infected, treatment-naive patients. HIV coreceptor usage was determined in the last pretherapy plasma sample for 977 individuals initiating HAART in British Columbia, Canada using the Monogram Trofile Tropism assay. Relative light unit (RLU) readouts from the Trofile assay, as well as HIV V3 loop sequence data, were examined as a function of baseline CD4 cell count for 953 (97%) samples with both phenotype and genotype data available. Median CCR5 RLUs were high for both R5 and X4-capable samples, while CXCR4 RLUs were orders of magnitude lower for X4 samples (p < 0.001). CCR5 RLUs in R5 samples (N = 799) increased with decreasing CD4 count (p < 0.001), but did not vary with plasma viral load (pVL) (p = 0.74). In X4 samples (N = 178), CCR5 RLUs decreased with decreasing CD4 count (p = 0.046) and decreasing pVL (p = 0.097), while CXCR4 RLUs increased with decreasing pVL (p = 0.0008) but did not vary with CD4 (p = 0.96). RLUs varied with the presence of substitutions at V3 loop positions 11, 25, and 6-8. The prevalence and impact of substitutions at codons 25 and 6-8 were CD4 dependent as was the presence of amino acid mixtures in the V3; substitutions at position 11 were CD4 independent. Assay RLU measures predictably vary with both immunological and virological parameters. The ability to predict X4 virus using genotypic determinants at positions 25 and 6-8 of the V3 loop is CD4 dependent, while position 11 appears to be CD4 independent.

Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection

PubMed Central

Hickling, Stephen; Hurst, Jacob; Meyerowitz, Jodi; Willberg, Christian B.; Robinson, Nicola; Brown, Helen; Kinloch, Sabine; Babiker, Abdel; Nwokolo, Nneka; Fox, Julie; Fidler, Sarah; Phillips, Rodney; Frater, John

2016-01-01

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches. PMID:27415828

Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia.

PubMed

Yirdaw, Kesetebirhan Delele; Hattingh, Susan

2015-01-01

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources.

Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia

PubMed Central

2015-01-01

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources. PMID:25961732

Day-On, Day-Off emtricitabine, tenofovir disoproxil fumarate and efavirenz single tablet regimen (DODO) as maintenance therapy in HIV-infected patients.

PubMed

Costantini, Andrea; Tontini, Chiara; Rocchi, Monia; Martini, Matteo; Butini, Luca

2018-06-01

Reduced dose schedules may be feasible options to simplify antiretroviral therapy (ART) in selected HIV-1-infected individuals. Efficacy and safety of a Day-on, Day-off (DODO) schedule of tenofovir disoproxil fumarate, emtricitabine and efavirenz (FTC/TDF/EFV) single tablet regimen (STR) was assessed. Twenty-seven patients were prescribed the DODO schedule and were monitored for 48 weeks. Switching criteria were: no previous ART failure, no AIDS-defining illnesses, T CD4 cell nadir >200/mmc, and HIV-RNA below detection limit (40 copies/mL) for at least six months. Clinical and laboratory data, including plasma HIV-RNA levels, T CD4 and CD8 counts, liver and kidney function, lipid levels and ultrasensitive C-reactive protein (us-CRP) were assessed at baseline, week 4, 12, 24, and 48. Statistical analysis was performed by paired Student's T-test for comparison between baseline and each time point and Chi square test for CD4/CD8 ratio comparison. In all, 26 out of 27 patients maintained plasma HIV-RNA levels below the detection limit through the entire follow-up. One patient experienced low level plasma HIV-RNA rebound at week 36 (47 copies/ml) and immediately reverted to the conventional dose schedule of FTC/TDF/EFV; plasma HIV-RNA was undetectable after four weeks. No major changes on liver and kidney function tests, lipid levels and us-CRP were observed. Although no profound modifications of T CD4 count were observed during follow-up, the CD4/CD8 ratio increased significantly at week 48 compared to the baseline (p<0.05). In conclusion, 48-week DODO administration of the fixed dose FTC/TDF/EFV STR combination was safe and effective in maintaining HIV viral replication below the detection limit in a selected group of HIV-1-infected individuals.

Changes in body mass index and hemoglobin concentration in breastfeeding women living with HIV with a CD4 count over 350: Results from 4 African countries (The ANRS 12174 trial)

PubMed Central

Engebretsen, Ingunn M. S.; Nagot, Nicolas; Meda, Nicolas Y.; Vallo, Roselyne; Kankasa, Chipepo; Tumwine, James K.; Singata, Mandisa; Hofmeyr, Justus G.; Van de Perre, Philippe; Tylleskär, Thorkild

2017-01-01

Introduction Breastfeeding is recommended for infants born to HIV-infected women in low-income settings. Both breastfeeding and HIV-infection are energy demanding. Our objective was to explore how exclusive and predominant breastfeeding changes body mass index (BMI) among breastfeeding HIV1-positive women participating in the ANRS12174 trial (clinical trial no NCT0064026). Methods HIV-positive women (n = 1 267) with CD4 count >350, intending to breastfeed HIV-negative infants were enrolled from Burkina Faso, South Africa, Uganda and Zambia and counselled on breastfeeding. N = 1 216 were included in the analysis. The trial compared Lamivudine and Lopinavir/Ritonavir as a peri-exposure prophylaxis. We ran a linear mixed-effect model with BMI as the dependent variable and exclusive or predominant breastfeeding duration as the key explanatory variable. Results Any breastfeeding or exclusive/predominant) breastfeeding was initiated by 99.6% and 98.6% of the mothers respectively in the first week after birth. The median (interquartile range: IQR) duration of the group that did any breastfeeding or the group that did exclusive /predominant breastfeeding were 9.5 (7.5; 10.6) and 5.8 (5.6; 5.9)) months, respectively. The median (IQR) age, BMI, CD4 count, and HIV viral load at baseline (day 7) were 27 (23.3; 31) years, 23.7 (21.3; 27.0) kg/m2, 530 (432.5; 668.5) cells/μl and 0.1 (0.8; 13.7)1000 copies/mL, respectively. No major change in mean BMI was seen in this cohort over a 50-week period during lactation. The mean change between 26 and 50 weeks after birth was 0.7 kg/m2. Baseline mean BMI (measured on day 7 postpartum) and CD4 count were positively associated with maternal BMI change, with a mean increase of 1.0 kg/m2 (0.9; 1.0) per each additional baseline-BMI kilogram and 0.3 kg/m2 (0.2; 0.5) for each additional CD4 cell/μl, respectively. Conclusion Breastfeeding was not negatively correlated with the BMI of HIV-1 infected Sub-Saharan African mothers. However, a higher baseline BMI and a CD4 count >500 cells/μl were associated with maternal BMI during the exclusive/ predominant breastfeeding period. Considering the benefits of breast milk for the infants and the recurrent results from different studies that breastfeeding is not harmful to the HIV-1-infected mothers, this study also supports the WHO 2016 guidelines on infant feeding that mothers living with HIV should breastfeed where formula is not safe for at least 12 months and up to 24 months, given that the right treatment or prophylaxis for the infection is administered. These findings and conclusions cannot be extrapolated to women who are immune-compromised or have AIDS. PMID:28486519

Changes in body mass index and hemoglobin concentration in breastfeeding women living with HIV with a CD4 count over 350: Results from 4 African countries (The ANRS 12174 trial).

PubMed

Somé, Eric Nagaonlé; Engebretsen, Ingunn M S; Nagot, Nicolas; Meda, Nicolas Y; Vallo, Roselyne; Kankasa, Chipepo; Tumwine, James K; Singata, Mandisa; Hofmeyr, Justus G; Van de Perre, Philippe; Tylleskär, Thorkild

2017-01-01

Breastfeeding is recommended for infants born to HIV-infected women in low-income settings. Both breastfeeding and HIV-infection are energy demanding. Our objective was to explore how exclusive and predominant breastfeeding changes body mass index (BMI) among breastfeeding HIV1-positive women participating in the ANRS12174 trial (clinical trial no NCT0064026). HIV-positive women (n = 1 267) with CD4 count >350, intending to breastfeed HIV-negative infants were enrolled from Burkina Faso, South Africa, Uganda and Zambia and counselled on breastfeeding. N = 1 216 were included in the analysis. The trial compared Lamivudine and Lopinavir/Ritonavir as a peri-exposure prophylaxis. We ran a linear mixed-effect model with BMI as the dependent variable and exclusive or predominant breastfeeding duration as the key explanatory variable. Any breastfeeding or exclusive/predominant) breastfeeding was initiated by 99.6% and 98.6% of the mothers respectively in the first week after birth. The median (interquartile range: IQR) duration of the group that did any breastfeeding or the group that did exclusive /predominant breastfeeding were 9.5 (7.5; 10.6) and 5.8 (5.6; 5.9)) months, respectively. The median (IQR) age, BMI, CD4 count, and HIV viral load at baseline (day 7) were 27 (23.3; 31) years, 23.7 (21.3; 27.0) kg/m2, 530 (432.5; 668.5) cells/μl and 0.1 (0.8; 13.7)1000 copies/mL, respectively. No major change in mean BMI was seen in this cohort over a 50-week period during lactation. The mean change between 26 and 50 weeks after birth was 0.7 kg/m2. Baseline mean BMI (measured on day 7 postpartum) and CD4 count were positively associated with maternal BMI change, with a mean increase of 1.0 kg/m2 (0.9; 1.0) per each additional baseline-BMI kilogram and 0.3 kg/m2 (0.2; 0.5) for each additional CD4 cell/μl, respectively. Breastfeeding was not negatively correlated with the BMI of HIV-1 infected Sub-Saharan African mothers. However, a higher baseline BMI and a CD4 count >500 cells/μl were associated with maternal BMI during the exclusive/ predominant breastfeeding period. Considering the benefits of breast milk for the infants and the recurrent results from different studies that breastfeeding is not harmful to the HIV-1-infected mothers, this study also supports the WHO 2016 guidelines on infant feeding that mothers living with HIV should breastfeed where formula is not safe for at least 12 months and up to 24 months, given that the right treatment or prophylaxis for the infection is administered. These findings and conclusions cannot be extrapolated to women who are immune-compromised or have AIDS.

Adherence to On-Time ART Drug Pick-Up and Its Association with CD4 Changes and Clinical Outcomes Amongst HIV Infected Adults on First-Line Antiretroviral Therapy in Nigerian Hospitals.

PubMed

Anoje, Chukwuemeka; Agu, Kenneth Anene; Oladele, Edward A; Badru, Titilope; Adedokun, Oluwasanmi; Oqua, Dorothy; Khamofu, Hadiza; Adebayo, Olufunso; Torpey, Kwasi; Chabikuli, Otto Nzapfurundi

2017-02-01

Medication adherence is a major determinant of antiretroviral treatment (ART) success. Promptness in medication refill pick-ups may give an indication of medication adherence. This study determined medication refill adherence among HIV positive patients on ART and its association with treatment outcomes in HIV treatment centers in Nigeria. This retrospective multi-center cohort study involved a review of ART refill records for 3534 HIV-positive patients aged 18-60 years who initiated first-line ART between January 2008 and December 2009 and were on therapy for ≥18 months after ART initiation. Drug refill records of these patients for 10 consecutive refill visits after ART initiation were analyzed. The first ten consecutive refill appointment-keeping rates after ART initiation ranged from 64.3 % to 76.1 % which decreased with successive visits. Altogether, 743 (21.1 %) patients were deemed adherent, meaning they picked up their drugs within 7 days of the drug refill appointment date on at least nine out of ten refill visits. The adherent group of patients had a mean CD4 cells increase of 206 ± 6.1 cells/dl after 12 months of ART compared to 186 ± 7.1 cells/dl reported among the nonadherent group (p = 0.0145). The proportion of patients in the adherent category who showed no OIs after 12 months on ART (81 %) was significantly higher when compared to the proportion in the non-adherent category (23.5 %), (p = 0.008). The multivariate analysis showed that the odds of being adherent was 2-3 times more in patients who had a baseline CD4 count of less than 200 cells/dl compared to those with a baseline CD4 of >350 cells/dl. (AOR 2.43, 95 % CI 1.62-3.66). In addition, for patients with baseline CD4 cell count of 201-350 cells/dl, the odds of being adherent was found to be 1.9 compared to those with baseline CD4 of greater than 350 cells/dl (AOR 1.93, 95 % CI 1.27-2.94). Pharmacy refill data can serve as an adherence measure. Adherence to on-time drug pickup on ≥90 % of refill appointments was associated with a better CD4 count response and a reduction in the presence of opportunistic infections in ART patients after 12 months of treatment.

HIV-1 disease progression in immune-competent HIV-1-infected and breastfeeding mothers participating in the ANRS 12174 clinical trial in Burkina Faso, South Africa, Uganda and Zambia: a cohort study

PubMed Central

Engebretsen, Ingunn M S; Nagot, Nicolas; Meda, Nicolas Yelbomkan; Vallo, Roselyne; Kankasa, Chipepo; Tumwine, James K; Singata-Madliki, Mandisa; Harper, Kim; Hofmeyr, G Justus; Van de Perre, Philippe; Tylleskär, Thorkild

2018-01-01

Objective We have assessed HIV-1 disease progression among HIV-1-positive mothers in relation to duration of any or exclusive breast feeding in the context of ANRS 12174 trial. Methods The analysis was completed on 203, 212, 272 and 529 HIV-1-positive and lactating mothers with CD4 count >350 cells/µL from Burkina Faso, South Africa, Uganda and Zambia, respectively. The trial compared lamivudine and lopinavir/ritonavir as a peri-exposure prophylaxis during a 50-week follow-up time. A multiple logistic regression model was run with the mothers’ weight, CD4 count and HIV-1 viral load as separate dependent variables, then combined into a dependent composite endpoint called HIV-1 disease progression where HIV-1 viral load was replaced by the HIV-1 clinical stage. Exclusive or predominant breast feeding (EPBF) and any breastfeeding duration were the key explanatory variables. Results In the adjusted model, the associations between EPBF duration and weight change, CD4 cell count and the HIV-1 viral load were consistently insignificant. The CD4 cell count was associated with a significantly higher mothers’ body mass index (BMI; a mean increase of 4.9 (95% CI 2.1 to 7.7) CD4 cells/µL per each additional kilogram per square metre of BMI) and haemoglobin concentration (19.4 (95% CI 11.4 to 27.4) CD4 cells/µL per each additional gram per decilitre of haemoglobin concentration). There was no significant association between EPBF duration and HIV-1 disease progression. A higher education level was a factor associated with a slower HIV-1 disease progression. Conclusion Breast feeding was not a risk factor for a faster progression of HIV-1 disease in mothers of this cohort with a baseline CD4 cell count >350 cells/µL. Trial registration number NCT0064026; Post-results. PMID:29626043

Clinical, virologic, and immunologic outcomes in lymphoma survivors and in cancer-free, HIV-1-infected patients: a matched cohort study.

PubMed

Spagnuolo, Vincenzo; Travi, Giovanna; Galli, Laura; Cossarini, Francesca; Guffanti, Monica; Gianotti, Nicola; Salpietro, Stefania; Lazzarin, Adriano; Castagna, Antonella

2013-08-01

The objective of this study was to compare immunologic, virologic, and clinical outcomes between living human immunodeficiency virus (HIV)-infected individuals who had a diagnosis of lymphoma versus outcomes in a control group of cancer-free, HIV-infected patients. In this matched cohort study, patients in the case group were survivors of incident lymphomas that occurred between 1997 and June 2010. Controls were living, cancer-free, HIV-infected patients who were matched to cases at a 4:1 ratio by age, sex, nadir CD4 cell count, and year of HIV diagnosis. The date of lymphoma diagnosis served as the baseline in cases and in the corresponding controls. In total, 62 patients (cases) who had lymphoma (20 with Hodgkin disease [HD] and 42 with non-Hodgkin lymphoma [NHL]) were compared with 211 controls. The overall median follow-up was 4.8 years (interquartile range, 2.0-7.9 years). The CD4 cell count at baseline was 278 cells/mm³ (interquartile range, 122-419 cells/mm³) in cases versus 421 cells/mm³ (interquartile range, 222-574 cells/mm³) in controls (P = .003). At the last available visit, the CD4 cell count was 412 cells/mm³ (range, 269-694 cells/mm³) in cases versus 518 cells/mm³ (interquartile range, 350-661 cells/mm³) in controls (P = .087). The proportion of patients who achieved virologic success increased from 30% at baseline to 74% at the last available visit in cases (P = .008) and from 51% to 81% in controls (P = .0286). Patients with HD reached higher CD4 cell counts at their last visit than patients with NHL (589 cells/mm³ [range, 400-841 cells/mm³] vs 332 cells/mm³ [interquartile range, 220-530 cells/mm³], respectively; P = .003). Virologic success was similar between patients with HD and patients with NHL at the last visit. Forty cases (65%) and 76 controls (36%) experienced at least 1 clinical event after baseline (P < .0001); cases were associated with a shorter time to occurrence of the first clinical event compared with controls (P < .0001). HIV-infected lymphoma survivors experienced more clinical events than controls, especially during the first year of follow-up, but they reached similar long-term immunologic and virologic outcomes. © 2013 American Cancer Society.

HIV Treatment Outcomes Among HIV-Infected, Opioid-Dependent Patients Receiving Buprenorphine/Naloxone Treatment within HIV Clinical Care Settings: Results From a Multisite Study

PubMed Central

Altice, Frederick L.; Bruce, R. Douglas; Lucas, Gregory M.; Lum, Paula J.; Korthuis, P. Todd; Flanigan, Timothy P.; Cunningham, Chinazo O.; Sullivan, Lynn E.; Vergara-Rodriguez, Pamela; Fiellin, David A.; Cajina, Adan; Botsko, Michael; Nandi, Vijay; Gourevitch, Marc N.; Finkelstein, Ruth

2012-01-01

Background Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. Methods HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. Results At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5.49]), and increased general health quality of life (β = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time. Conclusions Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality–of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population. PMID:21317590

Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study.

PubMed

Denny, Lynette; Hendricks, Bronwyn; Gordon, Chivaugn; Thomas, Florence; Hezareh, Marjan; Dobbelaere, Kurt; Durand, Christelle; Hervé, Caroline; Descamps, Dominique

2013-11-19

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18-25 years (N=120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix®; GlaxoSmithKline Vaccines) or placebo (Al[OH]3) at 0, 1 and 6 months (double-blind). HIV-negative women (N=30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection. Study ID: 107863/NCT00586339. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease

PubMed Central

2009-01-01

Objectives There is only little data on immune reconstitution in antiretroviral naïve AIDS-patients with toxoplasmosis. The observation of several cases with reduced increase of CD4-cells upon start of antiretroviral treatment (ART) prompted us to investigate the topic using the ClinSurv cohort. Methods 17 German HIV treatment centers contribute to ClinSurv, a multicentre observational cohort under the auspices of the Robert Koch Institute. We retrospectively selected all antiretroviral-naïve patients with toxoplasmic encephalitis (TE) and -as comparator group -with pneumocystosis (PCP) between January 1999 and December 2005. Results A total of 257 patients were included in the analysis, 61 with TE and 196 with PCP. Demographic baseline data showed differences with regard to gender, transmission group, and baseline CD4+ counts (60.9 vs. 44.7/μl, p = 0.022). After ART-initiation the increase in CD4+ lymphocytes was lower in the TE-versus the PCP-group in the first, second and fourth three-month-period (74.4 vs. 120.3/μl, p = 0.006; 96.6 vs. 136.2/μl, p = 0.021; 156.5 vs. 211.5/μl, p = 0.013). Viral load (VL) was higher in the PCP-group at baseline (4.46 log10cop/ml vs. 5.00 log10cop/ml, p = 0.008), while virological success of ART was equal. Conclusions Our data show for the first time that the average CD4+ T-cell increase of patients with toxoplasmosis is impaired compared to PCP-patients. Most clinicians would not be prepared to discontinue follow-up TE-therapy unless CD4+ counts of 200/μl are reached. Explanation for our finding might be the myelosuppressive side effect of pyrimethamine, possible interactions of toxoplasmosis therapy with ART, or an unknown direct biological influence of toxoplasmosis on immune restoration. PMID:19541584

Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease.

PubMed

Kastenbauer, U; Wolf, E; Kollan, C; Hamouda, O; Bogner, J R

2009-06-18

There is only little data on immune reconstitution in antiretroviral naive AIDS-patients with toxoplasmosis. The observation of several cases with reduced increase of CD4-cells upon start of antiretroviral treatment (ART) prompted us to investigate the topic using the ClinSurv cohort. 17 German HIV treatment centers contribute to ClinSurv, a multicentre observational cohort under the auspices of the Robert Koch Institute. We retrospectively selected all antiretroviral-naive patients with toxoplasmic encephalitis (TE) and - as comparator group - with pneumocystosis (PCP) between January 1999 and December 2005. A total of 257 patients were included in the analysis, 61 with TE and 196 with PCP. Demographic baseline data showed differences with regard to gender, transmission group, and baseline CD4 superset+ counts (60.9 vs. 44.7/microl, p = 0.022). After ART-initiation the increase in CD4 superset+ lymphocytes was lower in the TE- versus the PCP-group in the first, second and fourth three-month-period (74.4 vs. 120.3/microl, p = 0.006; 96.6 vs. 136.2/microl, p = 0.021; 156.5 vs. 211.5/microl, p = 0.013). Viral load (VL) was higher in the PCP-group at baseline (4.46 log subset10cop/ml vs. 5.00 log subset10cop/ml, p = 0.008), while virological success of ART was equal. Our data show for the first time that the average CD4 superset+ T-cell increase of patients with toxoplasmosis is impaired compared to PCP-patients. Most clinicians would not be prepared to discontinue follow-up TE-therapy unless CD4 superset+ counts of 200/microl are reached. Explanation for our finding might be the myelosuppressive side effect of pyrimethamine, possible interactions of toxoplasmosis therapy with ART, or an unknown direct biological influence of toxoplasmosis on immune restoration.

Normal CD4 Count Range among Healthy Nigerian Population in Ilorin.

PubMed

Afolabi, J K; Fadeyi, A; Desalu, O O; Durotoye, I A; Fawibe, A E; Adeboye, M A N; Olawumi, H O; Babatunde, A S; Ernest, S K; Aderibigbe, S A; Saadu, R; Salami, A K; Aboyeji, A P

For the establishment and monitoring of the immune status, CD4 count is critical. To determine the CD4 count range of apparently healthy Nigerians resident in Ilorin and compare with the national value. An automated blood analyzer was used to determine the full blood count and CD4 count. The percentage of CD4 count was derived by using other variables. Of the 1205 participants, the reference CD4 count (percentage of CD4) range for adult was 400 to 1288 cells/mm 3 (19%-48%) and for children was 582 to 3652 cells/mm 3 (17%-50%). CD4 count and percentage of CD4 were significantly ( P = .001) higher in females than in males, and the CD4 count declined significantly with increasing age ( r = -.174, P ≤ .0001). The percentage of CD4 count shows less variation with age ( r = -.051, P = .076). Adult residents of Ilorin had significantly lower absolute mean CD4 count (808 ± 260) than that of the national reference values of 847.0 ± 307.0 cells/mm 3 ( P = .001). We therefore advocate the use of CD4 count range derived in this study is lower than that of the national reference values.

Food insecurity may lead to incomplete HIV viral suppression and less immune reconstitution among HIV/hepatitis C virus-coinfected people.

PubMed

Aibibula, W; Cox, J; Hamelin, A-M; Moodie, Eem; Naimi, A I; McLinden, T; Klein, M B; Brassard, P

2018-02-01

The aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV). This study was conducted using data from the Food Security & HIV-HCV Sub-Study of the Canadian Co-Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity. The association between FI, HIV viral load, and CD4 count was assessed using a stabilized inverse probability weighted marginal structural model. A total of 725 HIV/HCV-coinfected people with 1973 person-visits over 3 years of follow-up contributed to this study. At baseline, 23% of participants experienced moderate food insecurity and 34% experienced severe food insecurity. The proportion of people with undetectable HIV viral load was 75% and the median CD4 count was 460 [interquartile range (IQR): 300-665] cells/μL. People experiencing severe food insecurity had 1.47 times [95% confidence interval (CI): 1.14, 1.88] the risk of having detectable HIV viral load and a 0.91-fold (95% CI: 0.84, 0.98) increase in CD4 count compared with people who were food secure. These findings provide evidence of the negative impact of food insecurity on HIV viral load and CD4 count among HIV/HCV-coinfected people. © 2017 British HIV Association.

Compact quadruple therapy with the lamivudine/zidovudine combination tablet plus abacavir and efavirenz, followed by the lamivudine/zidovudine/abacavir triple nucleoside tablet plus efavirenz in treatment-naïve HIV-infected adults.

PubMed

Ruane, Peter J; Parenti, David M; Margolis, David M; Shepp, David H; Babinchak, Timothy J; Van Kempen, Amy S; Kauf, Teresa L; Danehower, Susan A; Yau, Linda; Hessenthaler, Siegrid M; Goodwin, Diane; Hernandez, Jaime E

2003-01-01

To assess efficacy, safety, and adherence with compact quadruple therapy comprising one lamivudine 150-mg/zidovudine 300-mg tablet (COM) twice daily + one abacavir (ABC) 300-mg tablet twice daily + three efavirenz (EFV) 200-mg capsules at bedtime for 24 weeks, followed by one lamivudine 150-mg/zidovudine 300-mg/ABC 300-mg triple nucleoside tablet (TZV) twice daily + three EFV 200-mg capsules at bedtime for 24 weeks. A pilot 48-week, prospective, open-label trial in which 38 antiretroviral-naïve HIV-infected adults (baseline median HIV-1 RNA 5.1 log(10) copies/mL, CD4+ cell count 285/microL) received the above treatment and were monitored regularly with respect to plasma HIV-1 RNA levels, CD4+ cell counts, T-cell receptor excision circles (TRECs), adherence, and adverse events. At Week 48, intent-to-treat, switch-included analysis showed plasma HIV-1 RNA levels <400 copies/mL in 100% (29/29) of patients and <50 copies/mL in 93% (27/29); 59% of patients who achieved <50 copies/mL had <3 copies/mL (16/27). Similar virologic suppression was observed in patients with baseline HIV-1 RNA above or below 100000 copies/mL. HIV-1 RNA and CD4+ cell counts changed from baseline by a median of -3.4 log(10) copies/mL and +172 cells/microL, respectively. One virologic failure occurred at Week 16. Median TRECs/100000 peripheral blood lymphocytes increased 6-fold between baseline and Week 48. Median adherence rates were consistently 100% by self-report and 94% by pill count. Grade 2-4 treatment-related adverse events included dreams (16%), nausea (13%), decreased white cells (8%), dizziness (8%), sleep disorders (8%), and malaise and fatigue (8%). A suspected ABC hypersensitivity reaction occurred in 8% (3/38) of patients. COM/ABC/EFV or TZV/EFV produced potent, durable virologic suppression and immunologic benefits, was associated with high adherence rates, and was generally well tolerated.

Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.

PubMed

Lodi, Sara; Phillips, Andrew; Logan, Roger; Olson, Ashley; Costagliola, Dominique; Abgrall, Sophie; van Sighem, Ard; Reiss, Peter; Miró, José M; Ferrer, Elena; Justice, Amy; Gandhi, Neel; Bucher, Heiner C; Furrer, Hansjakob; Moreno, Santiago; Monge, Susana; Touloumi, Giota; Pantazis, Nikos; Sterne, Jonathan; Young, Jessica G; Meyer, Laurence; Seng, Rémonie; Dabis, Francois; Vandehende, Marie-Anne; Pérez-Hoyos, Santiago; Jarrín, Inma; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A

2015-08-01

Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL. We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders. Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9). The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART. National Institutes of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immunogenicity and Immunological Memory Induced by the 13-Valent Pneumococcal Conjugate Followed by the 23-Valent Polysaccharide Vaccine in HIV-Infected Adults.

PubMed

Farmaki, Paraskevi F; Chini, Maria C; Mangafas, Nikolaos M; Tzanoudaki, Marianna T; Piperi, Christina P; Lazanas, Marios Z; Spoulou, Vana S

2018-06-05

Vaccine-induced memory B-cell (MBC) subsets have distinct roles in the establishment of protective immunity; MBCs expressing nonswitched immunoglobulin M (IgM+ MBCs) replenish the MBC pool, whereas MBCs expressing isotype-switched immunoglobulin (sIg+ MBCs) differentiate into plasma cells upon antigen reencounter. We investigated immunogenicity and MBCs induced by combined 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPV23) in human immunodeficiency virus (HIV)-infected adults. Forty HIV-seropositive adults receiving ART with undetectable viral loads were enrolled. Seventeen had a CD4+ T-cell count of ≥400 cells/μL (group A), and 23 had a CD4+ T-cell count of 200-399 cells/μL (group B). All adults received PCV13 and, 1 year later, PPV23. Levels of IgM+ MBCs (defined as polysaccharide [PS]-specific CD19+CD10-CD27+CD21++IgM+ MBCs) and sIg+ MBCs (defined as PS-specific CD19+CD10-CD27+CD21++IgM- MBCs) and antibodies against PS14 and PS3 were measured prior and 1 month after each vaccination. Immunization caused a significant increase in PS antibodies, compared with levels at baseline (P < .001). Group B achieved significantly lower titers than group A (P < .05 for both PS14 and PS3). After receipt of PCV13, levels of IgM+ MBCs were unchanged, whereas levels of sIg+ MBCs increased significantly (P < .05 for PS14 and P < .001 for PS3). In contrast, following PPV23 receipt, levels of IgM+ MBCs were significantly reduced, and levels of sIg+ MBCs remained stable. A positive correlation was observed between baseline IgM+ and sIg+ MBC counts 1 month after PCV13 receipt but not after PPV23 receipt. PPV23 receipt 12 months after PCV13 receipt improved PCV13 immunogenicity. The reduction in the IgM+ MBC count observed after PPV23 receipt suggests that PPV23 has a depleting effect on PCV13-associated immunological memory. NCT03041051.

Prevalence and Predictors of Thyroid Dysfunction in Patients with HIV Infection and Acquired Immunodeficiency Syndrome: An Indian Perspective.

PubMed

Sharma, Neera; Sharma, Lokesh Kumar; Dutta, Deep; Gadpayle, Adesh Kisanji; Anand, Atul; Gaurav, Kumar; Mukherjee, Sabyasachi; Bansal, Rahul

2015-01-01

Background. Predictors of thyroid dysfunction in HIV are not well determined. This study aimed to determine the prevalence and predictors of thyroid dysfunction in HIV infected Indians. Methods. Consecutive HIV patients, 18-70 years of age, without any severe comorbid state, having at least 1-year follow-up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays. Results. From initially screened 527 patients, 359 patients (61.44 ± 39.42 months' disease duration), having good immune function [CD4 count >200 cell/mm(3): 90.25%; highly active antiretroviral therapy (HAART): 88.58%], were analyzed. Subclinical hypothyroidism (ScH) was the commonest thyroid dysfunction (14.76%) followed by sick euthyroid syndrome (SES) (5.29%) and isolated low TSH (3.1%). Anti-TPO antibody (TPOAb) was positive in 3.90%. Baseline CD4 count had inverse correlation with TPOAb after adjusting for age and body mass index. Stepwise linear regression revealed baseline CD4 count, TPOAb, and tuberculosis to be best predictors of ScH after adjusting for age, weight, duration of HIV, and history of opportunistic fungal and viral infections. Conclusion. Burden of thyroid dysfunction in chronic HIV infection with stable immune function is lower compared to pre-HAART era. Thyroid dysfunction is primarily of nonautoimmune origin, predominantly ScH. Severe immunodeficiency at disease onset, TPOAb positivity, and tuberculosis were best predictors of ScH.

Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection.

PubMed

Borges, Álvaro H; Neuhaus, Jacqueline; Babiker, Abdel G; Henry, Keith; Jain, Mamta K; Palfreeman, Adrian; Mugyenyi, Peter; Domingo, Pere; Hoffmann, Christian; Read, Tim R H; Pujari, Sanjay; Meulbroek, Michael; Johnson, Margaret; Wilkin, Timothy; Mitsuyasu, Ronald

2016-12-15

 In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts and human immunodeficiency virus (HIV) RNA between the study arms.  Incident malignancies in START were categorized into infection-related and infection-unrelated cancer. We used Cox models to assess factors associated with both cancer categories. We used sequential adjustment for baseline covariates, cancer risk factors, and HIV-specific variables to investigate potential mediators of cancer risk reduction with immediate cART.  There were 14 cancers among persons randomized to immediate cART (6 infection-related and 8 infection-unrelated) and 39 cancers in the deferred arm (23 infection-related and 16 infection-unrelated); hazard ratios of immediate vs deferred cART initiation were 0.26 (95% confidence interval [CI], .11-.64) for infection-related and 0.49 (95% CI, .21-1.15) for infection-unrelated cancer. Independent predictors of infection-related cancer were older age, higher body mass index, low- to middle-income region, HIV RNA, and baseline CD8 cell count. Older age and baseline CD8 cell count were independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level had little impact on the protective effect of immediate cART on infection-related cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.  Immediate cART initiation significantly reduces risk of cancer. Although limited by small sample size, this benefit does not appear to be solely attributable to HIV RNA suppression and may be also mediated by other mechanisms. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Effect of improved access to antiretroviral therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania.

PubMed

Mugusi, Sabina F; Mwita, Julius C; Francis, Joel M; Aboud, Said; Bakari, Muhammad; Aris, Eric A; Swai, Andrew B; Mugusi, Ferdinand M; Pallangyo, Kisali; Sandstrom, Eric

2010-05-28

Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004-Dec 2005 compared to those enrolled between 2006 and September 2008. Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/microl) with 65.7% having below 200 cells/microl. Females had higher CD4 cell counts (150 cells/microl) than males (109 cells/microl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/microl) compared to CD4 of 167 cells/microl in those seen later (2006-8) (p < 0.001). Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease.

Reversibility of peripheral blood leukocyte phenotypic and functional changes after exposure to and withdrawal from tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

PubMed

Weinhold, Kent J; Bukowski, Jack F; Brennan, Todd V; Noveck, Robert J; Staats, Janet S; Lin, Liwen; Stempora, Linda; Hammond, Constance; Wouters, Ann; Mojcik, Christopher F; Cheng, John; Collinge, Mark; Jesson, Michael I; Hazra, Anasuya; Biswas, Pinaki; Lan, Shuping; Clark, James D; Hodge, Jennifer A

2018-06-01

This study evaluated the short-term effects of tofacitinib treatment on peripheral blood leukocyte phenotype and function, and the reversibility of any such effects following treatment withdrawal in healthy volunteers. Cytomegalovirus (CMV)-seropositive subjects received oral tofacitinib 10 mg twice daily for 4 weeks and were followed for 4 weeks after drug withdrawal. There were slight increases in total lymphocyte and total T-cell counts during tofacitinib treatment, and B-cell counts increased by up to 26%. There were no significant changes in granulocyte or monocyte counts, or granulocyte function. Naïve and central memory T-cell counts increased during treatment, while all subsets of activated T cells were decreased by up to 69%. T-cell subsets other than effector memory cluster of differentiation (CD)4+, activated naïve CD4+ and effector CD8+ T-cell counts and B-cell counts, normalized 4 weeks after withdrawal. Following ex vivo activation, measures of CMV-specific T-cell responses, and antigen non-specific T-cell-mediated cytotoxicity and interferon (IFN)-γ production, decreased slightly. These T-cell functional changes were most pronounced at Day 15, partially normalized while still on tofacitinib and returned to baseline after drug withdrawal. Total natural killer (NK)-cell counts decreased by 33%, returning towards baseline after drug withdrawal. NK-cell function decreased during tofacitinib treatment, but without a consistent time course across measured parameters. However, markers of NK-cell-mediated cytotoxicity, antibody-dependent cellular cytotoxicity and IFN-γ production were decreased up to 42% 1 month after drug withdrawal. CMV DNA was not detectable in whole blood, and there were no cases of herpes zoster reactivation. No new safety concerns arose. In conclusion, the effect of short-term tofacitinib treatment on leukocyte composition and function in healthy CMV+ volunteers is modest and largely reversible 4 weeks after withdrawal. Copyright © 2018 Pfizer Inc. Published by Elsevier Inc. All rights reserved.

Ultrasensitive HIV-1 Viral Load as a Marker of Treatment Choice for Simplification Strategies.

PubMed

Lambert-Niclot, Sidonie; Grude, Maxime; Meynard, Jean-Luc; Marcelin, Anne-Geneviève; Valantin, Marc-Antoine; Flandre, Philippe; Izopet, Jacques; Moinot, Laetitia; Bouteloup, Vincent; Calvez, Vincent; Katlama, Christine; Girard, Pierre-Marie; Morand-Joubert, Laurence

2018-05-15

We pooled the results of three randomized trials that compared the efficacy of PI/r monotherapy and standard triple therapy as maintenance therapy and evaluated: 1) the distribution of ultrasensitive viral load (USVL) at week 96 (W96), 2) factors associated with virological success (VL<50 copy/mL) at W96, and 3) factors associated with USVL<1 copy/ml (c/ml) at W96. Virological failure was defined as two consecutive measurements of HIV-1 RNA viral load >50 copies/mL and was analyzed in intention-to-treat. USVL was measured with commercial standard Roche assay. A logistic model was used to investigate which variables were predictive of VF. The Fisher exact test was used to investigate differences in USVL at W96. Among 609 patients, 73% were male with a median age of 44.4 years (IQR 39.8-52.1), the treatment duration was four years, (2.4-7.6), baseline CD4/CD8 ratio 0.8 (0.6-1.10), baseline CD4 cell count 564/mm3 (422-707), and 59% presented a baseline USVL<1 copy/mL. At W96, the proportion of USVL<1 copy/mL was significantly lower for PI/r monotherapy than triple therapy (65% versus 74%; p=0.04). Overall, baseline USVL<1 copy/mL, triple therapy, and being female were associated with an USVL<1 copy/mL at W96 (p<0.0001, p=0.049 and p=0.006). For PI/r monotherapy, receiving DRV/r rather than LPV/r was associated with an USVL<1 copy/mL at W96 (p=0.03). Factors associated with virological success at W96 were higher baseline CD4 cell count (p=0.034) and baseline USVL<1 copy/mL (p=0.0005). Although PI/r monotherapy is not widely recommended, this strategy is still sometimes used and USVL determination for virologically-controlled patients may help to select the best candidates for PI/r monotherapy.

Population PK-PD analyses of CD25 occupancy, CD56bright NK cell expansion, and regulatory T cell reduction by daclizumab HYP in subjects with multiple sclerosis.

PubMed

Diao, Lei; Hang, Yaming; Othman, Ahmed A; Mehta, Devangi; Amaravadi, Lakshmi; Nestorov, Ivan; Tran, Jonathan Q

2016-11-01

Daclizumab high yield process (HYP) is a humanized IgG1 monoclonal antibody that binds to the α-subunit of the interleukin-2 receptor and is being developed for treatment of multiple sclerosis (MS). This manuscript characterized the pharmacokinetic-pharmacodynamic (PK-PD) relationships of daclizumab HYP in subjects with MS. Approximately 1400 subjects and 7000 PD measurements for each of three biomarkers [CD25 occupancy, CD56 bright natural killer (NK) cell count, regulatory T cell (Treg) count] from four clinical trials were analyzed using non-linear mixed effects modelling. Evaluated regimens included 150 or 300 mg subcutaneous (s.c.) every 4 weeks. CD25 occupancy was characterized using a sigmoidal maximum response (E max ) model. Upon daclizumab HYP treatment, CD25 saturation was rapid with complete saturation occurring after approximately 7 h and maintained when daclizumab HYP serum concentration was ≥5 mg l -1 . After the last 150 mg s.c. dose, unoccupied CD25 returned to baseline levels in approximately 24 weeks, with daclizumab HYP serum concentration approximately ≤1 mgl -1 1L. CD56 bright NK cell expansion was characterized using an indirect response model. Following daclizumab HYP 150 mg s.c. every 4 weeks, expansion plateaus approximately at week 36, at which the average maximum expansion ratio is 5.2. After the last dose, CD56 bright NK cells gradually declined to baseline levels within 24 weeks. Treg reduction was characterized by a sigmoidal E max model. Average maximum reduction of 60% occurred approximately 4 days post 150 mg s.c. dose. After the last dose, Tregs were projected to return to baseline levels in approximately 20 weeks. Robust PK-PD models of CD25 occupancy, CD56 bright NK cell expansion and Treg reduction by daclizumab HYP were developed to characterize its key pharmacodynamic effects in the target patient population. © 2016 The British Pharmacological Society.

Determinants of CD4 cell count change and time-to default from HAART; a comparison of separate and joint models.

PubMed

Tegegne, Awoke Seyoum; Ndlovu, Principal; Zewotir, Temesgen

2018-04-27

HIV has the most serious effects in Sub-Saharan African countries as compared to countries in other parts of the world. As part of these countries, Ethiopia has been affected significantly by the disease, and the burden of the disease has become worst in the Amhara Region, one of the eleven regions of the country. Being a defaulter or dropout of HIV patients from the treatment plays a significant role in treatment failure. The current research was conducted with the objective of comparing the performance of the joint and the separate modelling approaches in determining important factors that affect HIV patients' longitudinal CD4 cell count change and time to default from treatment. Longitudinal data was obtained from the records of 792 HIV adult patients at Felege-Hiwot Teaching and Specialized Hospital in Ethiopia. Two alternative approaches, namely separate and joint modeling data analyses, were conducted in the current study. Joint modeling was conducted for an analysis of the change of CD4 cell count and the time to default in the treatment. In the joint model, a generalized linear mixed effects model and Weibul survival sub-models were combined together for the repetitive measures of the CD4 cell count change and the number of follow-ups in which patients wait in the treatment. Finally, the two models were linked through their shared unobserved random effects using a shared parameter model. Both separate and joint modeling approach revealed a consistent result. However, the joint modeling approach was more parsimonious and fitted the given data well as compared to the separate one. Age, baseline CD4 cell count, marital status, sex, ownership of cell phone, adherence to HAART, disclosure of the disease and the number of follow-ups were important predictors for both the fluctuation of CD4 cell count and the time-to default from treatment. The inclusion of patient-specific variations in the analyses of the two outcomes improved the model significantly. Certain groups of patients were identified in the current investigation. The groups already identified had high fluctuation in the number of CD4 cell count and defaulted from HAART without any convincing reasons. Such patients need high intervention to adhere to the prescribed medication.

CD4+, CD8+, CD3+ cell counts and CD4+/CD8+ ratio among patients with mycobacterial diseases (leprosy, tuberculosis), HIV infections, and normal healthy adults: a comparative analysis of studies in different regions of India.

PubMed

Hussain, Tahziba; Kulshreshtha, K K; Yadav, V S; Katoch, Kiran

2015-01-01

In this study, we estimated the CD4+, CD8+, CD3+ cell counts and the CD4/CD8 ratio among normal healthy controls (adults and children), leprosy patients (without any complications and during reactional states), TB patients (with and without HIV), and HIV-positive patients (early infection and full-blown AIDS) and correlated the changes with disease progression. In our study, it was observed that among adults, CD4+ cell counts ranged from 518-1098, CD8+ from 312-952, whereas CD4/CD8 ratio from 0.75-2.30. Among children, both CD4+ and CD8+ cells were more and the CD4/CD8 ratio varied from 0.91-3.17. With regard to leprosy patients, we observed that CD4+ and CD8+ cell counts were lower among PB (pauci-bacillary) and MB (multi-bacillary) patients. CD4/CD8 ratio was 0.99 ± 0.28 among PB patients while the ratio was lower, 0.78 ± 0.20, among MB patients. CD4+ cell counts were raised during RR (reversal reactions) and ENL (erythema nodosum leprosum) among the PB and MB patients whereas the CD8+ cell counts were lower among PB and MB patients. CD4/CD8 ratio doubled during reactional episodes of RR and ENL. Among the HIV-negative tuberculosis (TB) patients, both the CD4+ and CD8+ cell counts were found to be less and the CD4/CD8 ratio varied between 0.53-1.75. Among the HIV-positive TB patients and HIV-positive patients, both the CD4+ and CD8+ cells were very less and ratio drops significantly. In the initial stages of infection, as CD4+ counts drop, an increase in the CD8+ cell counts was observed and the ratio declines. In full-blown cases, CD4+ cell counts were very low, 3-4 to 54 cells, CD8+ cells from 12-211 and the ratio drops too low. This study is the first of its kind in this region of the country and assumes importance since no other study has reported the values of CD4+ and CD8+ T-lymphocyte counts among patients with mycobacterial diseases (leprosy and TB), HIV infections along with normal healthy individuals of the region, and correlation with clinical presentations of patients.

[A multicenter study of correlation between peripheral lymphocyte counts and CD(+)4T cell counts in HIV/AIDS patients].

PubMed

Xie, Jing; Qiu, Zhifeng; Han, Yang; Li, Yanling; Song, Xiaojing; Li, Taisheng

2015-02-01

To evaluate the accuracy of lymphocyte count as a surrogate for CD(+)4T cell count in treatment-naїve HIV-infected adults. A total of 2 013 HIV-infected patients were screened at 23 sites in China. CD(+)4T cell counts were measured by flow cytometry. Correlation between CD(+)4T cell count and peripheral lymphocyte count were analyzed by spearman coefficient. AUCROC were used to evaluate the performance of lymphocyte count as a surrogate for CD(+)4T cell count. The lymphocyte count and CD(+)4T cell count of these 2 013 patients were (1 600 ± 670) × 10(6)/L and (244 ± 148) × 10(6)/L respectively. CD(+)4T cell count were positively correlated with lymphocyte count (r = 0.482, P < 0.000 1). AUCROC of lymphocyte count as a surrogate for CD(+)4T cell counts of <100×10(6)/L, <200×10(6)/L and <350×10(6)/L were 0.790 (95%CI 0.761-0.818, P < 0.000 1), 0.733 (95%CI 0.710-0.755, P < 0.000 1) and 0.732 (95%CI 0.706-0.758, P < 0.000 1) respectively. Lymphocyte count could be considerad as a potential surrogate marker for CD(+)4T cell count in HIV/AIDS patients not having access to T cell subset test by flowcytometry.

Treatment Response and Mortality among Patients Starting Antiretroviral Therapy with and without Kaposi Sarcoma: A Cohort Study

PubMed Central

Maskew, Mhairi; Fox, Matthew P.; van Cutsem, Gilles; Chu, Kathryn; MacPhail, Patrick; Boulle, Andrew; Egger, Matthias; Africa, for IeDEA Southern

2013-01-01

Background Improved survival among HIV-infected individuals on antiretroviral therapy (ART) has focused attention on AIDS-related cancers including Kaposi sarcoma (KS). However, the effect of KS on response to ART is not well-described in Southern Africa. We assessed the effect of KS on survival and immunologic and virologic treatment responses at 6- and 12-months after initiation of ART. Methods We analyzed prospectively collected data from a cohort of HIV-infected adults initiating ART in South Africa. Differences in mortality between those with and without KS at ART initiation were estimated with Cox proportional hazard models. Log-binomial models were used to assess differences in CD4 count response and HIV virologic suppression within a year of initiating treatment. Results Between January 2001–January 2008, 13,847 HIV-infected adults initiated ART at the study clinics. Those with KS at ART initiation (n = 247, 2%) were similar to those without KS (n = 13600,98%) with respect to age (35 vs. 35yrs), presenting CD4 count (74 vs. 85cells/mm3) and proportion on TB treatment (37% vs. 30%). In models adjusted for sex, baseline CD4 count, age, treatment site, tuberculosis and year of ART initiation, KS patients were over three times more likely to have died at any time after ART initiation (hazard ratio[HR]: 3.62; 95% CI: 2.71–4.84) than those without KS. The increased risk was highest within the first year on ART (HR: 4.05; 95% CI: 2.95–5.55) and attenuated thereafter (HR: 2.30; 95% CI: 1.08–4.89). Those with KS also gained, on average, 29 fewer CD4 cells (95% CI: 7–52cells/mm3) and were less likely to increase their CD4 count by 50 cells from baseline (RR: 1.43; 95% CI: 0.99–2.06) within the first 6-months of treatment. Conclusions HIV-infected adults presenting with KS have increased risk of mortality even after initiation of ART with the greatest risk in the first year. Among those who survive the first year on therapy, subjects with KS demonstrated a poorer immunologic response to ART than those without KS. PMID:23755122

Total lymphocyte count and subpopulation lymphocyte counts in relation to dietary intake and nutritional status of peritoneal dialysis patients.

PubMed

Grzegorzewska, Alicja E; Leander, Magdalena

2005-01-01

Dietary deficiency causes abnormalities in circulating lymphocyte counts. For the present paper, we evaluated correlations between total and subpopulation lymphocyte counts (TLC, SLCs) and parameters of nutrition in peritoneal dialysis (PD) patients. Studies were carried out in 55 patients treated with PD for 22.2 +/- 11.4 months. Parameters of nutritional status included total body mass, lean body mass (LBM), body mass index (BMI), and laboratory indices [total protein, albumin, iron, ferritin, and total iron binding capacity (TIBC)]. The SLCs were evaluated using flow cytometry. Positive correlations were seen between TLC and dietary intake of niacin; TLC and CD8 and CD16+56 counts and energy delivered from protein; CD4 count and beta-carotene and monounsaturated fatty acids 17:1 intake; and CD19 count and potassium, copper, vitamin A, and beta-carotene intake. Anorexia negatively influenced CD19 count. Serum albumin showed correlations with CD4 and CD19 counts, and LBM with CD19 count. A higher CD19 count was connected with a higher red blood cell count, hemoglobin, and hematocrit. Correlations were observed between TIBC and TLC and CD3 and CD8 counts, and between serum Fe and TLC and CD3 and CD4 counts. Patients with a higher CD19 count showed a better clinical-laboratory score, especially less weakness. Patients with a higher CD4 count had less expressed insomnia. Quantities of ingested vitamins and minerals influence lymphocyte counts in the peripheral blood of PD patients. Evaluation of TLC and SLCs is helpful in monitoring the effectiveness of nutrition in these patients.

Restoring Cytokine Balance in HIV-Positive Individuals with Low CD4 T Cell Counts

PubMed Central

Valdivia, Anddre; Ly, Judy; Gonzalez, Leslie; Hussain, Parveen; Saing, Tommy; Islamoglu, Hicret; Pearce, Daniel; Ochoa, Cesar

2017-01-01

Abstract HIV infects and destroys CD4+ T cells leading to a compromised immune system. In a double-blinded study, a group of HIV-infected individuals with CD4+ T cell counts below 350 cells/mm3 were given either an empty liposomal supplement or a liposomal glutathione (L-GSH) supplement to take over a 3-month period. Baseline measurements in HIV-positive subjects show a significant decrease in levels of interleukin (IL)-12, IL-2, and interferon (IFN)-γ, along with a substantial increase in the levels of IL-6, IL-10, transforming growth factor (TGF)-β, and free radicals, compared to healthy individuals. Supplementation of HIV-positive subjects with L-GSH for 3 months resulted in a notable increase in the levels of IL-12, IL-2, and IFN-γ, with a concomitant decrease in the levels of IL-6, IL-10, and free radicals, and stabilization in the levels of TGF-β, IL-1, and IL-17, compared to their placebo counterparts. Levels of free radicals in CD4+ T cells stabilized, while GSH levels increased in the treatment group. Those in the placebo group showed no significant difference throughout the study. In summary, supplementation with L-GSH in HIV-infected individuals with CD4+ T cell counts below 350 cells/mm3 can help restore redox homeostasis and cytokine balance, therefore aiding the immune system to control opportunistic infections. PMID:28398068

Body mass index, immune status, and virological control in HIV-infected men who have sex with men.

PubMed

Blashill, Aaron J; Mayer, Kenneth H; Crane, Heidi M; Grasso, Chris; Safren, Steven A

2013-01-01

Prior cross-sectional studies have found inconsistent relationships between body mass index (BMI) and disease progression in HIV-infected individuals. Cross-sectional and longitudinal analyses were conducted on data from a sample of 864 HIV-infected men who have sex with men (MSM) obtained from a large, nationally distributed HIV clinical cohort. Of the 864 HIV-infected MSM, 394 (46%) were of normal weight, 363 (42%) were overweight, and 107 (12%) were obese at baseline. The baseline CD4 count was 493 (standard error [SE] = 9), with viral load (log10) = 2.4 (SE = .04), and 561 (65%) were virologically suppressed. Over time, controlling for viral load, highly active antiretroviral therapy (HAART) adherence, age, and race/ethnicity, overweight and obese HIV-infected men possessed higher CD4 counts than that of normal weight HIV-infected men. Further, overweight and obese men possessed lower viral loads than that of normal weight HIV-infected men. For HIV-infected MSM, in this longitudinal cohort study, possessing a heavier than normal BMI is longitudinally associated with improved immunological health.

The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome.

PubMed

Baris, Hatice Ezgi; Baris, Safa; Karakoc-Aydiner, Elif; Gokce, Ibrahim; Yildiz, Nurdan; Cicekkoku, Dilek; Ogulur, Ismail; Ozen, Ahmet; Alpay, Harika; Barlan, Isil

2016-05-01

The severity and duration of immunosuppression caused by corticosteroids (CSs) usage have not been extensively studied. We aimed to investigate the effects of CSs on the various compartments of immune system in relation to timing of initiation and persistence of therapy. Pediatric patients with idiopathic nephrotic syndrome (NS) treated with 2 mg/kg/day prednisolone and healthy control (HC) were enrolled. Blood samples were drawn for immunologic analyses at baseline and at the first and second weeks and first, second, and third months of CS therapy in addition to first and second weeks and first, second, and third months of discontinuation. Fourteen patients (M/F, 7/7) between 1 and 8 years old were evaluated. Untreated NS exhibited high absolute lymphocyte count (ALC)(p = 0.010), absolute CD3(+) T cells (p = 0.020) and absolute CD8(+) T cells (p = 0.006) compared to HC. Suppression in ALC was observed and nadir value was noted at first month of therapy compared to baseline (p = 0.002). The CD4(+) (p = 0.036) and CD8(+) T cell (p = 0.013) counts decreased significantly at the first week of treatment compared to baseline. While baseline B cell counts was indifferent from HC, gradually increased in 2 weeks of CS initiation and decreased during the treatment with a statistical significance compared to HC (p = 0.010). However, after cessation of CS, B cell counts continued to decline and found to be significantly different than baseline at first week (p = 0.008) and at third month (p = 0.040). Apart from baseline lymphocyte subset changing observed in untreated NS patients, our data implies that T cells were suppressed very early in the CS treatment. Interestingly, depressed B cell counts were detected later but persisted even after CS cessation. Due to early decrease in T cells, it would be beneficial to assume the patients as immunosuppressed at the very beginning of CS treatment to avoid infections. • Corticosteroids (CSs) are widely used for a variety of diseases including nephrotic syndrome, which is related with complex immune disturbance including T and B cells dysfunctions. • CSs induce neutrophilic leukocytosis concomitant with lymphopenia and eosinopenia leading to immunosupression. What is New: • T cell subsets and proliferation are susceptible to CSs more than B cells; however, the reversibility is faster with dose reduction in CS. • The change of B cells and B cell subtypes (CD27 (+) memory) shows prolonged effect of CSs on B cells which may alter antibody production even after 3 months of CSs cessation.

Risk factors and frequency of tuberculosis-associated immune reconstitution inflammatory syndrome among HIV/Tuberculosis co-infected patients in Southern India.

PubMed

Vignesh, Ramachandran; Swathirajan, Chinnambedu R; Solomon, Sunil S; Shankar, Esaki Muthu; Murugavel, Kailapuri G

2017-01-01

Immune reconstitution inflammatory syndrome (IRIS) continues to be a complication in HIV/tuberculosis (TB) co-infected patients initiating highly active antiretroviral therapy (HAART). The aim of this study was to evaluate the risk factors associated with developing IRIS to identify a possible biomarker to predict or diagnose IRIS in patients initiating HAART. A total of 175 HIV/TB co-infected patients initiating HAART were followed up longitudinally during September 2010 to May 2013 attending a HIV care clinic in Chennai. Patients were followed up longitudinally after HAART initiation and baseline demographic, laboratory parameters and treatment characteristics between patients with IRIS events and those without IRIS events were compared. Chi-square or Fisher's exact test for categorical variables and a Wilcoxon rank-sum test for continuous variables were performed using SPSS, version 12.0 software. Patients with IRIS had a significantly lower median baseline CD4+ T-cell count (P = 0.0039). There were no differences in terms of sex, CD4 T-cell %, plasma viral load, time interval between initiating ATT and HAART between the IRIS and non-IRIS patients. Low CD4+ T-cell count (<100 cells/μL) could be used as a marker to screen and monitor patients initiating HAART.

Long-term immunologic and virologic responses on raltegravir-containing regimens among ART-experienced participants in the HIV Outpatient Study

PubMed Central

Buchacz, Kate; Wiegand, Ryan; Armon, Carl; Chmiel, Joan S.; Wood, Kathleen; Brooks, John T.; Palella, Frank J.

2015-01-01

Objectives Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data exist on long-term outcomes in routine HIV care. Methods We studied ART-experienced HIV outpatient study (HOPS) participants seen at 10 US HIV-specialty clinics during 2007–2011. We identified patients who started (baseline date) either continuous ≥30 days of RAL-containing or RAL-sparing ART, and used propensity score (PS) matching methods to account for baseline clinical and demographic differences. We used Kaplan–Meier methods and log-rank tests for the matched subsets to evaluate probability of death, achieving HIV RNA <50 copies/ml, and CD4 cell count (CD4) increase of ≥50 cells mm−3 during follow-up. Results Among 784 RAL-exposed and 1062 RAL-unexposed patients, 472 from each group were matched by PS. At baseline, the 472 RAL-exposed patients (mean nadir CD4, 205 cells mm−3; mean baseline CD4, 460 cells mm−3; HIV RNA <50 copies ml−1 in 61%; mean years on prescribed ART, 7.5) were similar to RAL unexposed. During a mean follow-up of over 3 years, mortality rates and immunologic and virologic trajectories did not differ between the two groups. Among patients with detectable baseline HIV RNA levels, 76% of RAL-exposed and 63% of RAL-unexposed achieved HIV RNA <50 copies ml−1 (P=0.51); 69 and 58%, respectively, achieved a CD4 increase ≥50 cells mm−3 (P=0.70). Discussion In our large cohort of US ART-experienced patients with a wide spectrum of clinical history, similar outcomes were observed when prescribed RAL containing versus other contemporary ART. PMID:26126549

A novel Acute Retroviral Syndrome Severity Score predicts the key surrogate markers for HIV-1 disease progression.

PubMed

Braun, Dominique L; Kouyos, Roger; Oberle, Corinna; Grube, Christina; Joos, Beda; Fellay, Jacques; McLaren, Paul J; Kuster, Herbert; Günthard, Huldrych F

2014-01-01

Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption). Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+ cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40). The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Factors associated with antiretroviral treatment initiation amongst HIV-positive individuals linked to care within a universal test and treat programme: early findings of the ANRS 12249 TasP trial in rural South Africa

PubMed Central

Boyer, Sylvie; Iwuji, Collins; Gosset, Andréa; Protopopescu, Camelia; Okesola, Nonhlanhla; Plazy, Mélanie; Spire, Bruno; Orne-Gliemann, Joanna; McGrath, Nuala; Pillay, Deenan; Dabis, François; Larmarange, Joseph

2016-01-01

Prompt uptake of antiretroviral treatment (ART) is essential to ensure the success of universal test and treat (UTT) strategies to prevent HIV transmission in high-prevalence settings. We describe ART initiation rates and associated factors within an ongoing UTT cluster-randomized trial in rural South Africa. HIV-positive individuals were offered immediate ART in the intervention arm vs. national guidelines recommended initiation (CD4≤350 cells/mm3) in the control arm. We used data collected up to July 2015 among the ART-eligible individuals linked to TasP clinics before January 2015. ART initiation rates at one (M1), three (M3) and six months (M6) from baseline visit were described by cluster and CD4 count strata (cells/mm3) and other eligibility criteria: ≤100; 100–200; 200–350; CD4>350 with WHO stage 3/4 or pregnancy; CD4>350 without WHO stage 3/4 or pregnancy. A Cox model accounting for covariate effect changes over time was used to assess factors associated with ART initiation. The 514 participants had a median [interquartile range] follow-up duration of 1.08 [0.69; 2.07] months until ART initiation or last visit. ART initiation rates at M1 varied substantially (36.9% in the group CD4>350 without WHO stage 3/4 or pregnancy, and 55.2–71.8% in the three groups with CD4≤350) but less at M6 (from 85.3% in the first group to 96.1–98.3% in the three other groups). Factors associated with lower ART initiation at M1 were a higher CD4 count and attending clinics with both high patient load and higher cluster HIV prevalence. After M1, having a regular partner was the only factor associated with higher likelihood of ART initiation. These findings suggest good ART uptake within a UTT setting, even among individuals with high CD4 count. However, inadequate staffing and healthcare professional practices could result in prioritizing ART initiation in patients with the lowest CD4 counts. PMID:27421051

Biomarker and Histopathology Evaluation of Patients with Recurrent Glioblastoma Treated with Galunisertib, Lomustine, or the Combination of Galunisertib and Lomustine

PubMed Central

Capper, David; von Deimling, Andreas; Brandes, Alba A.; Carpentier, Antoine F.; Kesari, Santosh; Sepulveda-Sanchez, Juan M.; Wheeler, Helen R.; Chinot, Olivier; Cher, Lawrence; Steinbach, Joachim P.; Specenier, Pol; Rodon, Jordi; Cleverly, Ann; Smith, Claire; Gueorguieva, Ivelina; Miles, Colin; Guba, Susan C.; Desaiah, Durisala; Estrem, Shawn T.; Lahn, Michael M.; Wick, Wolfgang

2017-01-01

Galunisertib, a Transforming growth factor-βRI (TGF-βRI) kinase inhibitor, blocks TGF-β-mediated tumor growth in glioblastoma. In a three-arm study of galunisertib (300 mg/day) monotherapy (intermittent dosing; each cycle =14 days on/14 days off), lomustine monotherapy, and galunisertib plus lomustine therapy, baseline tumor tissue was evaluated to identify markers associated with tumor stage (e.g., histopathology, Ki67, glial fibrillary acidic protein) and TGF-β-related signaling (e.g., pSMAD2). Other pharmacodynamic assessments included chemokine, cytokine, and T cell subsets alterations. 158 patients were randomized to galunisertib plus lomustine (n = 79), galunisertib (n = 39) and placebo+lomustine (n = 40). In 127 of these patients, tissue was adequate for central pathology review and biomarker work. Isocitrate dehydrogenase (IDH1) negative glioblastoma patients with baseline pSMAD2+ in cytoplasm had median overall survival (OS) 9.5 months vs. 6.9 months for patients with no tumor pSMAD2 expression (p = 0.4574). Eight patients were IDH1 R132H+ and had a median OS of 10.4 months compared to 6.9 months for patients with negative IDH1 R132H (p = 0.5452). IDH1 status was associated with numerically higher plasma macrophage-derived chemokine (MDC/CCL22), higher whole blood FOXP3, and reduced tumor CD3+ T cell counts. Compared to the baseline, treatment with galunisertib monotherapy preserved CD4+ T cell counts, eosinophils, lymphocytes, and the CD4/CD8 ratio. The T-regulatory cell compartment was associated with better OS with MDC/CCL22 as a prominent prognostic marker. PMID:28481241

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?

PubMed Central

Ghiglione, Yanina; Hormanstorfer, Macarena; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D.; Pando, María de los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Sued, Omar

2018-01-01

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied. PMID:29342870

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

PubMed

Turk, Gabriela; Ghiglione, Yanina; Hormanstorfer, Macarena; Laufer, Natalia; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Holgado, María Pía; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D; Pando, María de Los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Pury, Pedro A; Sued, Omar

2018-01-13

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4⁺ T-cell activation ( p < 0.05). However, none of these cytokines had good predictive values to distinguish "progressors" from "non-progressors". Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

Improved Survival of HIV-1-Infected Patients with Progressive Multifocal Leukoencephalopathy Receiving Early 5-Drug Combination Antiretroviral Therapy

PubMed Central

Hendel-Chavez, Houria; Dulioust, Anne; Pakianather, Sophie; Mazet, Anne-Aurélie; de Goer de Herve, Marie-Ghislaine; Lancar, Rémi; Lascaux, Anne-Sophie; Porte, Lydie; Delfraissy, Jean-François; Taoufik, Yassine

2011-01-01

Background Progressive multifocal leukoencephalopathy (PML), a rare devastating demyelinating disease caused by the polyomavirus JC (JCV), occurs in severely immunocompromised patients, most of whom have advanced-stage HIV infection. Despite combination antiretroviral therapy (cART), 50% of patients die within 6 months of PML onset. We conducted a multicenter, open-label pilot trial evaluating the survival benefit of a five-drug cART designed to accelerate HIV replication decay and JCV-specific immune recovery. Methods and Findings All the patients received an optimized cART with three or more drugs for 12 months, plus the fusion inhibitor enfuvirtide during the first 6 months. The main endpoint was the one-year survival rate. A total of 28 patients were enrolled. At entry, median CD4+ T-cell count was 53 per microliter and 86% of patients had detectable plasma HIV RNA and CSF JCV DNA levels. Seven patients died, all before month 4. The one-year survival estimate was 0.75 (95% confidence interval, 0.61 to 0.93). At month 6, JCV DNA was undetectable in the CSF of 81% of survivors. At month 12, 81% of patients had undetectable plasma HIV RNA, and the median CD4+ T-cell increment was 105 per microliter. In univariate analysis, higher total and naive CD4+ T-cell counts and lower CSF JCV DNA level at baseline were associated with better survival. JCV-specific functional memory CD4+ T-cell responses, based on a proliferation assay, were detected in 4% of patients at baseline and 43% at M12 (P = 0.008). Conclusions The early use of five-drug cART after PML diagnosis appears to improve survival. This is associated with recovery of anti-JCV T-cell responses and JCV clearance from CSF. A low CD4+ T-cell count (particularly naive subset) and high JCV DNA copies in CSF at PML diagnosis appear to be risk factors for death. Trial Registration ClinicalTrials.gov NCT00120367 PMID:21738597

Long-term mortality in HIV-positive individuals virally suppressed for >3 years with incomplete CD4 recovery.

PubMed

Engsig, Frederik N; Zangerle, Robert; Katsarou, Olga; Dabis, Francois; Reiss, Peter; Gill, John; Porter, Kholoud; Sabin, Caroline; Riordan, Andrew; Fätkenheuer, Gerd; Gutiérrez, Félix; Raffi, Francois; Kirk, Ole; Mary-Krause, Murielle; Stephan, Christoph; de Olalla, Patricia Garcia; Guest, Jodie; Samji, Hasina; Castagna, Antonella; d'Arminio Monforte, Antonella; Skaletz-Rorowski, Adriane; Ramos, Jose; Lapadula, Giuseppe; Mussini, Cristina; Force, Lluís; Meyer, Laurence; Lampe, Fiona; Boufassa, Faroudy; Bucher, Heiner C; De Wit, Stéphane; Burkholder, Greer A; Teira, Ramon; Justice, Amy C; Sterling, Tim R; M Crane, Heidi; Gerstoft, Jan; Grarup, Jesper; May, Margaret; Chêne, Geneviève; Ingle, Suzanne M; Sterne, Jonathan; Obel, Niels

2014-05-01

Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression (≤500 HIV type 1 RNA copies/mL) for >3 years with CD4 count ≤200 cells/µL at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/µL. The increased mortality was seen across different patient groups and for all causes of death. Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality.

Ten year experience with antiretroviral treatment in Cambodia: Trends in patient characteristics and treatment outcomes.

PubMed

Lay, Phirum; An, Sokkab; Soeung, Sunpiseth; Srey, Pich Sovannary; Thai, Sopheak; Lynen, Lutgarde; Griensven, Johan van

2017-01-01

Although HIV disease stage at ART initiation critically determines ART outcomes, few reports have longitudinally monitored this within Asia. Using prospectively collected data from a large ART program at Sihanouk Hospital Center of Hope in Cambodia, we report on the change in patient characteristics and outcomes over a ten-year period. We conducted a retrospective analysis including all adults (≥ 18 years old) starting ART from March 2003-March 2013 in a non-governmental hospital in Phnom Penh, Cambodia. The cumulative incidence of death, lost to follow-up (LTFU), attrition (death or LTFU) and first line treatment failure were calculated using Kaplan-Meier methods. Independent risk factors for these outcomes were determined using Cox regression modeling. Over the ten-year period, 3581 patients initiated ART with a median follow-up time of 4.8 years (IQR 2.8-7.2). The median age was 35 years (IQR 30-41), 54% were female. The median CD4 count at ART initiation increased from 22 cells/μL (IQR 4-129) in 2003 to 218 (IQR 57-302) in 2013. Over the 10 year period, a total of 282 (7.9%) individuals died and 433 (12.1%) were defined LTFU. Program attrition (died or LTFU) was 11.1% (95% CI: 10.1%- 12.4%) at one year, 16.3% (95% CI: 15.1%-17.6%) at three years, 19.8% (95% CI: 18.5%-21.2%) at five years and 23.3% (95% CI: 21.6-25.1) at ten years. Male sex and low baseline body mass index (BMI) were associated with increased attrition. Factors independently associated with mortality included a low baseline CD4 count, older age, male sex, low baseline BMI and hepatitis B co-infection. Individuals aged above 40 years old had an increased risk of mortality but were less likely to LTFU. There were a total of 137 individuals with first line ART failure starting second line treatment. The probability of first line failure was estimated at 2.8% (95% CI: 2.3%-3.4%) at 3 years, 4.6% (95% CI: 3.9%-5.5%) at 5 years and 7.8% (95% CI 4.8%-12.5%) at ten years of ART. The probability was particularly high in the first few program years. A lower risk was observed among individuals starting ART during the 2006-2008 period. Factors independently associated with an increased risk of treatment failure included ART-experience, NVP-based ART and a baseline CD4 count below 200 cells/μL. Overall program outcomes were fair, and generally compare well to other reports from the region. Despite gradually earlier initiation of ART over the ten year period, ART is still initiated at too low CD4 count levels, warranting increased efforts for early HIV diagnosis and enrolment/retention into HIV care. Tailored strategies for poor prognostic groups (older age, male, low BMI) should be designed and evaluated.

Does provision of point-of-care CD4 technology and early knowledge of CD4 levels affect early initiation and retention on antiretroviral treatment in HIV-positive pregnant women in the context of Option B+ for PMTCT?

PubMed

Mangwiro, Alexio-Zambezi; Makomva, Kudzai; Bhattacharya, Antoinette; Bhattacharya, Gaurav; Gotora, Tendai; Owen, Mila; Mushavi, Angela; Mangwanya, Douglas; Zinyowera, Sekesai; Rusakaniko, Simbarashe; Mugurungi, Owen; Zizhou, Simukai; Busumani, William; Masuka, Nyasha

2014-11-01

Evidence for Elimination (E4E) is a collaborative project established in 2012 as part of the INSPIRE (INtegrating and Scaling up PMTCT through Implementation REsearch) initiative. E4E is a cluster-randomized trial with 2 arms; Standard of care and "POC Plus" [in which point-of-care (POC) CD4 devices and related counseling support are provided]; aimed at improving retention-in-care of HIV-infected pregnant women and mothers. In November 2013, Zimbabwe adopted Option B+ for HIV-positive pregnant women under which antiretroviral treatment eligibility is no longer based on CD4 count. However, Ministry of Health and Child Care guidelines still require baseline and 6-monthly CD4 testing for treatment monitoring, until viral load testing becomes widely available. Considering the current limited capacity for viral-load testing, the significant investments in CD4 testing already made and the historical reliance on CD4 by health care workers for determining eligibility for antiretroviral treatment, E4E seeks to compare the impact of the provision of POC CD4 technology and early knowledge of CD4 levels on retention-in-care at 12 months, with the current standard of routine, laboratory-based CD4 testing. The study also compares rates of initiation and time-to-initiation between the 2 arms and according to level of maternal CD4 count, the cost of retaining HIV-positive pregnant women in care and the acceptability and feasibility of POC CD4 in the context of Option B+. Outcome measures are derived from routine health systems data. E4E will provide data on POC CD4 testing and retention-in-care associated with Option B+ and serve as an early learning platform to inform implementation of Option B+ in Zimbabwe.

Effect of Improved access to Antiretroviral Therapy on clinical characteristics of patients enrolled in the HIV care and treatment clinic, at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania

PubMed Central

2010-01-01

Background Sub-Saharan Africa has been severely affected by the HIV and AIDS pandemic. Global efforts at improving care and treatment has included scaling up use of antiretroviral therapy (ART). In Tanzania, HIV care and treatment program, including the provision of free ART started in 2004 with a pilot program at Muhimbili National Hospital in Dar es Salaam. This study describes the socio-demographic and clinical features of patients enrolled at the care and treatment clinic at MNH, Dar es Salaam, Tanzania. Methods A cross-sectional study looking at baseline characteristics of patients enrolled at the HIV clinic at MNH between June 2004 - Dec 2005 compared to those enrolled between 2006 and September 2008. Results Of all enrolled patients, 2408 (58.5%) were used for analysis. More females than males were attending the clinic. Their baseline median CD4 cell count was low (136 cells/μl) with 65.7% having below 200 cells/μl. Females had higher CD4 cell counts (150 cells/μl) than males (109 cells/μl) p < 0.001). The most common presenting features were skin rash and/or itching (51.6%); progressive weight loss (32.7%) and fever (23.4). Patients enrolled earlier at the clinic (2004-5) were significantly more symptomatic and had significantly lower CD4 cell count (127 cells/μl) compared to CD4 of 167 cells/μl in those seen later (2006-8) (p < 0.001). Conclusion Patients enrolled to the MNH HIV clinic were predominantly females, and presented with advanced immune-deficiency. Improved access to HIV care and treatment services seems to be associated with patients' early presentation to the clinics in the course of HIV disease. PMID:20509892

Sustained CD4+ T cell-driven lymphopenia without a compensatory IL-7/IL-15 response among high-grade glioma patients treated with radiation and temozolomide

PubMed Central

Ellsworth, Susannah; Balmanoukian, Ani; Kos, Ferdynand; Nirschl, Christopher J; Nirschl, Thomas R; Grossman, Stuart A; Luznik, Leo; Drake, Charles G

2014-01-01

Prolonged lymphopenia correlating with decreased survival commonly occurs among glioma patients undergoing radiation therapy (RT) and temozolomide (TMZ) treatment. To better understand the pathophysiology of this phenomenon, we prospectively monitored serum cytokine levels and lymphocyte subsets in 15 high-grade glioma patients undergoing combined radiation and TMZ (referred to as RT/TMZ) treatment. Sufficient data for analysis were acquired from 11 of the patients initially enrolled. Lymphocyte phenotyping data were obtained using cytofluorometric analysis and serum cytokine levels were measured using the a multiplex bead-based assays. Total lymphocyte counts (TLCs) were > 1000 cells per μL peripheral blood in 10/11 patients at baseline, but dropped significantly after treatment. Specifically, after RT/TMZ therapy, the TLCs were found to be < 500 cells/μL in 2/11 patients, 500–1000 cells/μL in 7/11 patients, and > 1000 cells/μL in the remaining 2 patients. Among residual mononuclear blood cells, we observed a proportional drop in B and CD4+ T cells but not in CD8+ T lymphocytes. Natural killer cells remained to near-to-baseline levels and there was a transient and slight (insignificant) increase in regulatory T cells (Tregs). The circulating levels of IL-7 and IL-15 remained low despite marked drops in both the total and CD4+ T lymphocyte counts. Thus, patients with malignant glioma undergoing RT/TMZ treatment exhibit a marked decline in TLCs, affecting both CD4+ T cells and B lymphocytes, in the absence of a compensatory increase in interleukin-7 levels. The failure to mount an appropriate homeostatic cytokine response may be responsible for the prolonged lymphopenia frequently observed in these patients. PMID:24790790

Reliable and accurate CD4+ T cell count and percent by the portable flow cytometer CyFlow MiniPOC and "CD4 Easy Count Kit-Dry", as revealed by the comparison with the gold standard dual platform technology.

PubMed

Nasi, Milena; De Biasi, Sara; Bianchini, Elena; Gibellini, Lara; Pinti, Marcello; Scacchetti, Tiziana; Trenti, Tommaso; Borghi, Vanni; Mussini, Cristina; Cossarizza, Andrea

2015-01-01

An accurate and affordable CD4+ T cells count is an essential tool in the fight against HIV/AIDS. Flow cytometry (FCM) is the "gold standard" for counting such cells, but this technique is expensive and requires sophisticated equipment, temperature-sensitive monoclonal antibodies (mAbs) and trained personnel. The lack of access to technical support and quality assurance programs thus limits the use of FCM in resource-constrained countries. We have tested the accuracy, the precision and the carry-over contamination of Partec CyFlow MiniPOC, a portable and economically affordable flow cytometer designed for CD4+ count and percentage, used along with the "CD4% Count Kit-Dry". Venous blood from 59 adult HIV+ patients (age: 25-58 years; 43 males and 16 females) was collected and stained with the "MiniPOC CD4% Count Kit-Dry". CD4+ count and percentage were then determined in triplicate by the CyFlow MiniPOC. In parallel, CD4 count was performed using mAbs and a CyFlow Counter, or by a dual platform system (from Beckman Coulter) based upon Cytomic FC500 ("Cytostat tetrachrome kit" for mAbs) and Coulter HmX Hematology Analyzer (for absolute cell count). The accuracy of CyFlow MiniPOC against Cytomic FC500 showed a correlation coefficient (CC) of 0.98 and 0.97 for CD4+ count and percentage, respectively. The accuracy of CyFlow MiniPOC against CyFlow Counter showed a CC of 0.99 and 0.99 for CD4 T cell count and percentage, respectively. CyFlow MiniPOC showed an excellent repeatability: CD4+ cell count and percentage were analyzed on two instruments, with an intra-assay precision below ± 5% deviation. Finally, there was no carry-over contamination for samples at all CD4 values, regardless of their position in the sequence of analysis. The cost-effective CyFlow MiniPOC produces rapid, reliable and accurate results that are fully comparable with those from highly expensive dual platform systems.

Factors involved in treatment durability and immunological recovery in a cohort of HIV-positive patients receiving atazanavir-based regimens

PubMed Central

Giacomelli, Andrea; Oreni, Letizia; Franzetti, Marco; Di Cristo, Valentina; Vergani, Barbara; Morosi, Manuela; Colella, Elisa; Galli, Massimo; Rusconi, Stefano

2014-01-01

Introduction Since antiretroviral therapy must be taken lifelong, persistence and safety have become the goals to achieve. Protease inhibitors, in particular atazanavir (ATV) with or without ritonavir (r), represent a highly prescribed class in real life long-term treatment. Methods We conducted a retrospective cohort study in HIV-1-positive patients who were followed at the Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan. Data regarding viral load, CD4 lymphocytes and the mean blood chemistry parameters were collected at baseline, first, third, sixth months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and time-dependent probability to reach a CD4 cells count >500 cells/µL were evaluated with Kaplan-Meier curve and Cox model. Results A total of 1030 patients were evaluated: 183 received therapy with ATV/r as naïve, 653 switched to ATV/r as a second or following line and 194 switched to unboosted ATV from previous ATV-free regimens. A total of 138 patients shifted to unboosted ATV from a previous ATV/r regimen (17 from naïve ATV/r and 121 from experienced ATV/r). The median duration of therapy was 38 months (95% CI 29–73) in ATV/r naïve patients, 36 months (95% CI 23–53) in unboosted ATV group and 35 months (95% CI 31–43) in patients switched to ATV/r. We observed no significant difference in the persistence of the three regimens (p=0.149). Female (HR=1.317; 95% CI 1.073–1.616 p=0.008) and patients with CD4<200 cells/µL at baseline (HR=1.433 95% CI 1.086–1.892 p=0.011) were at increased risk of regimen interruption, whereas starting therapy with a backbone containing abacavir (HR=0.725; 95% CI 0.533–0.987 p=0.041) resulted protective. In multivariate analysis no significant difference between the three regimens was observed regarding reaching a count of CD4 cells >500 cells/µL. Factors associated to a poor CD4 gain were each extra Log of viral load at baseline (HR=0.915; 95% CI 0.852–0.982 p=0.014) and CD4<200 cells/µL at ATV start (HR=0.197; 95%CI 0.138–0.281 p<0.0001); conversely, females (HR=1.262; 95%CI 1.032–1.543 p=0.023) had a higher probability of CD4 recovery. Conclusions Antiretroviral regimens containing atazanavir with or without ritonavir were durable and well tolerated, an elevated viral load and CD4 <200 cells/µL at baseline resulted related to regimen discontinuation and reduced CD4 recovery. PMID:25397574

Implementation and Operational Research: Integration of PMTCT and Antenatal Services Improves Combination Antiretroviral Therapy Uptake for HIV-Positive Pregnant Women in Southern Zambia: A Prototype for Option B+?

PubMed

Herlihy, Julie M; Hamomba, Leoda; Bonawitz, Rachael; Goggin, Caitlin E; Sambambi, Kennedy; Mwale, Jonas; Musonda, Victor; Musokatwane, Kebby; Hopkins, Kathryn L; Semrau, Katherine; Hammond, Emily E; Duncan, Julie; Knapp, Anna B; Thea, Donald M

2015-12-01

Early initiation of combination antiretroviral therapy (cART) for HIV-positive pregnant women can decrease vertical transmission to less than 5%. Programmatic barriers to early cART include decentralized care, disease-stage assessment delays, and loss to follow-up. Our intervention had 3 components: integrated HIV and antenatal services in 1 location with 1 provider, laboratory courier to expedite CD4 counts, and community-based follow-up of women-infant pairs to improve prevention of mother-to-child transmission attendance. Preintervention HIV-positive pregnant women were referred to HIV clinics for disease-stage assessment and cART initiation for advanced disease (CD4 count <350 cells/μL or WHO stage >2). We used a quasi-experimental design with preintervention/postintervention evaluations at 6 government antenatal clinics (ANCs) in Southern Province, Zambia. Retrospective clinical data were collected from clinic registers during a 7-month baseline period. Postintervention data were collected from all antiretroviral therapy-naive, HIV-positive pregnant women and their infants presenting to ANC from December 2011 to June 2013. Data from 510 baseline women-infant pairs were analyzed and 624 pregnant women were enrolled during the intervention period. The proportion of HIV-positive pregnant women receiving CD4 counts increased from 50.6% to 77.2% [relative risk (RR) = 1.81; 95% confidence interval (CI): 1.57 to 2.08; P < 0.01]. The proportion of cART-eligible pregnant women initiated on cART increased from 27.5% to 71.5% (RR = 2.25; 95% CI: 1.78 to 2.83; P < 0.01). The proportion of eligible HIV-exposed infants with documented 6-week HIV PCR test increased from 41.9% to 55.8% (RR = 1.33; 95% CI: 1.18 to 1.51; P < 0.01). Integration of HIV care into ANC and community-based support improved uptake of CD4 counts, proportion of cART-eligible women initiated on cART, and infants tested.

Risk factors for mortality among HIV-positive patients with and without active tuberculosis in Dar es Salaam, Tanzania.

PubMed

Mugusi, Sabina F; Ngaimisi, Eliford; Janabi, Mohamed Y; Mugusi, Ferdinand M; Minzi, Omary M S; Sasi, Philip G; Bakari, Muhammad; Lindquist, Lars; Aklillu, Eleni; Sandstrom, Eric G

2012-01-01

The aim of this study was to describe risk factors for mortality and clinical characteristics of HIV-infected patients with and without tuberculosis (TB) coinfection. A cohort of HIV-infected patients with CD4(+) T-cell counts of ≤200 cells/μl was recruited, consisting of 255 HIV-infected patients without active TB and 231 patients with active TB. All received a well-supervised treatment with an efavirenz-based HAART, and those coinfected with TB received appropriate anti-TB treatment. They were followed up for 48 weeks after HAART initiation. Common presenting symptoms in HIV-only patients were fever (36.5%), headache (34.5%), skin rash (34.5%) and weight loss (32%), while in HIV-TB patients the symptoms were weight loss (58%), cough (57.6%), night sweats (44.6%) and fever (34.2%). HIV-TB patients had significantly lower body mass index, Karnofsky scores and haemoglobin levels compared to those infected with HIV only, despite similar baseline CD4(+) T-cell counts. Overall, 12 (4.7%) HIV patients developed TB and 7 (3%) HIV-TB patients had worsening of their TB symptoms during the study period. Mortality was similar in the two groups, being 10.9% (16 deaths per 100 person years) and 11.3% (17 deaths per 100 person years) in HIV-only and HIV-TB patients, respectively. Overall, more males (13.1%) died compared to females (9.6%). Predictors of mortality were presence of oral candidiasis, Kaposi's sarcoma, low Karnofsky score, and low baseline white blood cell and CD4(+) T-cell counts. The outcomes following well-supervised treatment of HIV-TB patients are similar to those in patients with HIV alone. Predictors of mortality were those of advanced disease.

Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

PubMed Central

2010-01-01

Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain. PMID:21182796

Failure to achieve immunological recovery in HIV-infected patients with clinical and virological success after 10 years of combined ART: role of treatment course.

PubMed

Raffi, François; Le Moing, Vincent; Assuied, Alex; Habak, Sofiane; Spire, Bruno; Cazanave, Charles; Billaud, Eric; Dellamonica, Pierre; Ferry, Tristan; Fagard, Catherine; Leport, Catherine

2017-01-01

We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. Failure of CD4 response (CD4 >500/mm 3 ) was associated with age ≥40 years at baseline (P < 0.001), CD4 cell counts ≤500/mm 3 at month 4 (P = 0.016) or month 12 (P < 0.001) and ≥3 months of cART interruption (P = 0.016). Factors associated with failure to achieve complete immunological response (CD4 >500/mm 3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P < 0.001) or month 12 (P < 0.001), ≥3 months of cumulative cART interruption (P = 0.011), ≥3 antiretroviral regimens (P = 0.009) and ≤4 treatment lines (P = 0.015). Baseline CD4 and CD4:CD8 ratio were not predictors of the 10 year immunological outcomes. In this therapeutic cohort of patients starting first-generation PI-containing cART in 1997-99, poor initial immunological response had a negative impact on 10 year CD4 and CD4 plus CD4:CD8 ratio response, despite prolonged virological success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK.

PubMed

Rockstroh, Jürgen K; DeJesus, Edwin; Lennox, Jeffrey L; Yazdanpanah, Yazdan; Saag, Michael S; Wan, Hong; Rodgers, Anthony J; Walker, Monica L; Miller, Michael; DiNubile, Mark J; Nguyen, Bach-Yen; Teppler, Hedy; Leavitt, Randi; Sklar, Peter

2013-05-01

STARTMRK, a phase III noninferiority trial of raltegravir-based versus efavirenz-based therapy in treatment-naive patients, remained blinded until its conclusion at 5 years. We now report the final study results. Previously untreated patients without baseline resistance to efavirenz, tenofovir, or emtricitabine were eligible for a randomized study of tenofovir/emtricitabine plus either raltegravir or efavirenz. Yearly analyses were planned, with primary and secondary end points stipulated at weeks 48 and 96, respectively. The primary efficacy outcome was the percentage of patients with viral RNA (vRNA) levels <50 copies per milliliter counting noncompleters as failures (NC=F). Changes from baseline CD4 count were computed using an observed-failure approach to missing data. No formal hypotheses were formulated for testing at week 240. Overall, 71 of 281 raltegravir recipients (25%) and 98 of 282 efavirenz recipients (35%) discontinued the study; discontinuations due to adverse events occurred in 14 (5%) and 28 (10%) patients in the respective groups. In the primary NC=F efficacy analysis at week 240, 198 of 279 (71.0%) raltegravir recipients and 171 of 279 (61.3%) efavirenz recipients had vRNA levels <50 copies per milliliter, yielding a treatment difference {Δ [95% confidence interval (CI)] = 9.5 (1.7 to 17.3)}. Generally comparable between-treatment differences were seen in both the protocol-stipulated sensitivity analyses and the prespecified subgroup analyses. The mean (95% CI) increments in baseline CD4 counts at week 240 were 374 and 312 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Δ(95% CI) = 62 (22 to 102)]. Overall, significantly fewer raltegravir than efavirenz recipients experienced neuropsychiatric side effects (39.1% vs 64.2%, P < 0.001) or drug-related clinical adverse events (52.0% vs 80.1%, P < 0.001). In this exploratory analysis of combination therapy with tenofovir/emtricitabine in treatment-naive patients at week 240, vRNA suppression rates and increases in baseline CD4 counts were significantly higher in raltegravir than efavirenz recipients. Over the entire study, fewer patients experienced neuropsychiatric and drug-related adverse events in the raltegravir group than in the efavirenz group. Based on better virologic and immunologic outcomes after 240 weeks, raltegravir/tenofovir/emtricitabine seemed to have superior efficacy compared with efavirenz/tenofovir/emtricitabine.

Characterization of Functional Antibody and Memory B-Cell Responses to pH1N1 Monovalent Vaccine in HIV-Infected Children and Youth

PubMed Central

Curtis, Donna J.; Muresan, Petronella; Nachman, Sharon; Fenton, Terence; Richardson, Kelly M.; Dominguez, Teresa; Flynn, Patricia M.; Spector, Stephen A.; Cunningham, Coleen K.; Bloom, Anthony; Weinberg, Adriana

2015-01-01

Objectives We investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children. Methods Ninety subjects 4 to <25 years of age received two double doses of pH1N1 vaccine. Serum and cells were frozen at baseline, after each vaccination, and at 28 weeks post-immunization. Hemagglutination inhibition (HAI) titers, avidity indices (AI), B-cell subsets, and pH1N1 IgG and IgA antigen secreting cells (ASC) were measured at baseline and after each vaccination. Neutralizing antibodies and pH1N1-specific Th1, Th2 and Tfh cytokines were measured at baseline and post-dose 1. Results At entry, 26 (29%) subjects had pH1N1 protective HAI titers (≥1:40). pH1N1-specific HAI, neutralizing titers, AI, IgG ASC, IL-2 and IL-4 increased in response to vaccination (p<0.05), but IgA ASC, IL-5, IL-13, IL-21, IFNγ and B-cell subsets did not change. Subjects with baseline HAI ≥1:40 had significantly greater increases in IgG ASC and AI after immunization compared with those with HAI <1:40. Neutralizing titers and AI after vaccination increased with older age. High pH1N1 HAI responses were associated with increased IgG ASC, IFNγ, IL-2, microneutralizion titers, and AI. Microneutralization titers after vaccination increased with high IgG ASC and IL-2 responses. IgG ASC also increased with high IFNγ responses. CD4% and viral load did not predict the immune responses post-vaccination, but the B-cell distribution did. Notably, vaccine immunogenicity increased with high CD19+CD21+CD27+% resting memory, high CD19+CD10+CD27+% immature activated, low CD19+CD21-CD27-CD20-% tissue-like, low CD19+CD21-CD27-CD20-% transitional and low CD19+CD38+HLADR+% activated B-cell subsets. Conclusions HIV-infected children on HAART mount a broad B-cell memory response to pH1N1 vaccine, which was higher for subjects with baseline HAI≥1:40 and increased with age, presumably due to prior exposure to pH1N1 or to other influenza vaccination/infection. The response to the vaccine was dependent on B-cell subset distribution, but not on CD4 counts or viral load. Trial Registration ClinicalTrials.gov NCT00992836 PMID:25785995

CD4+ T-cell-guided structured treatment interruptions of antiretroviral therapy in HIV disease: projecting beyond clinical trials.

PubMed

Yazdanpanah, Yazdan; Wolf, Lindsey L; Anglaret, Xavier; Gabillard, Delphine; Walensky, Rochelle P; Moh, Raoul; Danel, Christine; Sloan, Caroline E; Losina, Elena; Freedberg, Kenneth A

2010-01-01

International trials have shown that CD4+ T-cell-guided structured treatment interruptions (STI) of antiretroviral therapy (ART) lead to worse outcomes than continuous treatment. We simulated continuous ART and STI strategies with higher CD4+ T-cell interruption/reintroduction thresholds than those assessed in actual trials. Using a model of HIV, we simulated cohorts of African adults with different baseline CD4+ T-cell counts (< or = 200; 201-350; and 351-500 cells/microl). We varied ART initiation criteria (immediate; CD4+ T-cell count < 350 cells/microl or > or = 350 cells/microl with severe HIV-related disease; and CD4+ T-cell count <200 cells/microl or > or = 200 cells/microl with severe HIV-related disease), and ART interruption/reintroduction thresholds (350/250; 500/350; and 700/500 cells/microl). First-line therapy was non-nucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line therapy was protease inhibitor (PI)-based. STI generally reduced life expectancy compared with continuous ART. Life expectancy increased with earlier ART initiation and higher interruption/reintroduction thresholds. STI reduced life expectancy by 48-69 and 11-30 months compared with continuous ART when interruption/reintroduction thresholds were 350/250 and 500/350 cells/microl, depending on ART initiation criteria. When patients interrupted/reintroduced ART at 700/500 cells/microl, life expectancies ranged from 2 months lower to 1 month higher than continuous ART. STI-related life expectancy increased with decreased risk of virological resistance after ART interruptions. STI with NNRTI-based regimens was almost always less effective than continuous treatment, regardless of interruption/reintroduction thresholds. The risks associated with STI decrease only if patients start ART earlier, interrupt/reintroduce treatment at very high CD4+ T-cell thresholds (700/500 cells/microl) and use first-line medications with higher resistance barriers, such as PIs.

Significant CD4, CD8, and CD19 lymphopenia in peripheral blood of sarcoidosis patients correlates with severe disease manifestations.

PubMed

Sweiss, Nadera J; Salloum, Rafah; Gandhi, Seema; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P; Moller, David R; Garcia, Joe G N; Niewold, Timothy B

2010-02-05

Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4x10(-10)). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment.

Significant CD4, CD8, and CD19 Lymphopenia in Peripheral Blood of Sarcoidosis Patients Correlates with Severe Disease Manifestations

PubMed Central

Sweiss, Nadera J.; Salloum, Rafah; Ghandi, Seema; Alegre, Maria-Luisa; Sawaqed, Ray; Badaracco, Maria; Pursell, Kenneth; Pitrak, David; Baughman, Robert P.; Moller, David R.; Garcia, Joe G. N.; Niewold, Timothy B.

2010-01-01

Background Sarcoidosis is a poorly understood chronic inflammatory condition. Infiltration of affected organs by lymphocytes is characteristic of sarcoidosis, however previous reports suggest that circulating lymphocyte counts are low in some patients with the disease. The goal of this study was to evaluate lymphocyte subsets in peripheral blood in a cohort of sarcoidosis patients to determine the prevalence, severity, and clinical features associated with lymphopenia in major lymphocyte subsets. Methodology/Principal Findings Lymphocyte subsets in 28 sarcoid patients were analyzed using flow cytometry to determine the percentage of CD4, CD8, and CD19 positive cells. Greater than 50% of patients had abnormally low CD4, CD8, or CD19 counts (p<4×10−10). Lymphopenia was profound in some cases, and five of the patients had absolute CD4 counts below 200. CD4, CD8, and CD19 lymphocyte subset counts were significantly correlated (Spearman's rho 0.57, p = 0.0017), and 10 patients had low counts in all three subsets. Patients with severe organ system involvement including neurologic, cardiac, ocular, and advanced pulmonary disease had lower lymphocyte subset counts as a group than those patients with less severe manifestations (CD4 p = 0.0043, CD8 p = 0.026, CD19 p = 0.033). No significant relationships were observed between various medical therapies and lymphocyte counts, and lymphopenia was present in patients who were not receiving any medical therapy. Conclusions/Significance Significant lymphopenia involving CD4, CD8, and CD19 positive cells was common in sarcoidosis patients and correlated with disease severity. Our findings suggest that lymphopenia relates more to disease pathology than medical treatment. PMID:20140091

Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution.

PubMed

Lewis, Joanna; Walker, A Sarah; Castro, Hannah; De Rossi, Anita; Gibb, Diana M; Giaquinto, Carlo; Klein, Nigel; Callard, Robin

2012-02-15

Effective therapies and reduced AIDS-related morbidity and mortality have shifted the focus in pediatric human immunodeficiency virus (HIV) from minimizing short-term disease progression to maintaining optimal long-term health. We describe the effects of children's age and pre-antiretroviral therapy (ART) CD4 count on long-term CD4 T-cell reconstitution. CD4 counts in perinatally HIV-infected, therapy-naive children in the Paediatric European Network for the Treatment of AIDS 5 trial were monitored following initiation of ART for a median 5.7 years. In a substudy, naive and memory CD4 counts were recorded. Age-standardized measurements were analyzed using monophasic, asymptotic nonlinear mixed-effects models. One hundred twenty-seven children were studied. Older children had lower age-adjusted CD4 counts in the long term and at treatment initiation (P < .001). At all ages, lower counts before treatment were associated with impaired recovery (P < .001). Age-adjusted naive CD4 counts increased on a timescale comparable to overall CD4 T-cell reconstitution, whereas age-adjusted memory CD4 counts increased less, albeit on a faster timescale. It appears the immature immune system can recover well from HIV infection via the naive pool. However, this potential is progressively damaged with age and/or duration of infection. Current guidelines may therefore not optimize long-term immunological health.

Rifaximin has a Marginal Impact on Microbial Translocation, T-cell Activation and Inflammation in HIV-Positive Immune Non-responders to Antiretroviral Therapy – ACTG A5286

PubMed Central

Tenorio, Allan R.; Chan, Ellen S.; Bosch, Ronald J.; Macatangay, Bernard J. C.; Read, Sarah W.; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M.; Jacobson, Jeffrey M.; Landay, Alan L.; Wilson, Cara C.; Mellors, John W.; Keshavarzian, Ali; Rodriguez, Benigno; Aziz, Mariam; Presti, Rachel; Deeks, Steven; Ebiasah, Ruth; Myers, Laurie; Borowski, LuAnn; Plants, Jill; Palm, David A.; Weibel, Derek; Putnam, Beverly; Lindsey, Elizabeth; Player, Amy; Albrecht, Mary; Kershaw, Andrea; Sax, Paul; Keenan, Cheryl; Walton, Patricia; Baum, Jane; Stroberg, Todd; Hughes, Valery; Coster, Laura; Kumar, Princy N.; Yin, Michael T.; Noel-Connor, Jolene; Tebas, Pablo; Thomas, Aleshia; Davis, Charles E.; Redfield, Robert R.; Sbrolla, Amy; Flynn, Teri; Davis, Traci; Whitely, Kim; Singh, Baljinder; Swaminathan, Shobha; McGregor, Donna; Palella, Frank; Aberg, Judith; Cavanagh, Karen; Santana Bagur, Jorge L.; Flores, Olga Méndez; Fritsche, Janice; Sha, Beverly; Slamowitz, Debbie; Valle, Sandra; Tashima, Karen; Patterson, Helen; Harber, Heather; Para, Michael; Eaton, Molly; Maddox, Dale; Currier, Judith; Cajahuaringa, Vanessa; Luetkemeyer, Annie; Dwyer, Jay; Fichtenbaum, Carl J.; Saemann, Michelle; Ray, Graham; Campbell, Thomas; Fischl, Margaret A.; Bolivar, Hector; Oakes, Jonathan; Chicurel-Bayard, Miriam; Tripoli, Christine; Weinman, D. Renee; Adams, Mary; Hurley, Christine; Dunaway, Shelia; Storey, Sheryl; Klebert, Michael; Royal, Michael

2015-01-01

Background. Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). Methods. HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4+ T-cell counts <350 cells/mm3 were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Results. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8+T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. Conclusions. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8+T-cell activation. Trial registration number. NCT01466595. PMID:25214516

Impaired Upregulation of the Costimulatory Molecules, CD27 and CD28, on CD4+ T Cells from HIV Patients Receiving ART Is Associated with Poor Proliferative Responses.

PubMed

Tanaskovic, Sara; Price, Patricia; French, Martyn A; Fernandez, Sonia

2017-02-01

HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4 + T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4 + T cell deficiency on ART. Aviremic HIV patients with nadir CD4 + T cell counts <100 cells/μL and who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (<350 cells/μL; n = 13) or normal (>500 cells/μL; n = 20) CD4 + T cell counts. Ten healthy controls were also recruited. CD4 + T cell proliferation (Ki67) and upregulation of costimulatory molecules (CD27 and CD28) after anti-CD3 stimulation were assessed by flow cytometry. Results were related to proportions of CD4 + T cells expressing markers of T cell senescence (CD57), activation (HLA-DR), and apoptotic potential (Fas). Expression of CD27 and/or CD28 on uncultured CD4 + T cells was similar in patients with normal CD4 + T cell counts and healthy controls, but lower in patients with low CD4 + T cell counts. Proportions of CD4 + T cells expressing CD27 and/or CD28 correlated inversely with CD4 + T cell expression of CD57, HLA-DR, and Fas. After anti-CD3 stimulation, induction of CD27 hi CD28 hi expression was independent of CD4 + T cell counts, but lower in HIV patients than in healthy controls. Induction of CD27 hi CD28 hi expression correlated with induction of Ki67 expression in total, naïve, and CD31 + naïve CD4 + T cells from patients. In HIV patients responding to ART, impaired induction of CD27 and CD28 on CD4 + T cells after stimulation with anti-CD3 is associated with poor proliferative responses as well as greater CD4 + T cell activation and immunosenescence.

Electrochemical magneto-actuated biosensor for CD4 count in AIDS diagnosis and monitoring.

PubMed

Carinelli, S; Xufré Ballesteros, C; Martí, M; Alegret, S; Pividori, M I

2015-12-15

The counting of CD4(+) T lymphocytes is a clinical parameter used for AIDS diagnosis and follow-up. As this disease is particularly prevalent in developing countries, simple and affordable CD4 cell counting methods are urgently needed in resource-limited settings. This paper describes an electrochemical magneto-actuated biosensor for CD4 count in whole blood. The CD4(+) T lymphocytes were isolated, preconcentrated and labeled from 100 μL of whole blood by immunomagnetic separation with magnetic particles modified with antiCD3 antibodies. The captured cells were labeled with a biotinylated antiCD4 antibody, followed by the reaction with the electrochemical reporter streptavidin-peroxidase conjugate. The limit of detection for the CD4 counting magneto-actuated biosensor in whole blood was as low as 44 cells μL(-1) while the logistic range was found to be from 89 to 912 cells μL(-1), which spans the whole medical interest range for CD4 counts in AIDS patients. The electrochemical detection together with the immunomagnetic separation confers high sensitivity, resulting in a rapid, inexpensive, robust, user-friendly method for CD4 counting. This approach is a promising alternative for the costly standard flow cytometry and suitable as diagnostic tool at decentralized practitioner sites in low resource settings, especially in less developed countries. Copyright © 2015 Elsevier B.V. All rights reserved.

Low CD1c + myeloid dendritic cell counts correlated with a high risk of rapid disease progression during early HIV-1 infection.

PubMed

Diao, Yingying; Geng, Wenqing; Fan, Xuejie; Cui, Hualu; Sun, Hong; Jiang, Yongjun; Wang, Yanan; Sun, Amy; Shang, Hong

2015-08-19

During early HIV-1 infection (EHI), the interaction between the immune response and the virus determines disease progression. Although CD1c + myeloid dendritic cells (mDCs) can trigger the immune response, the relationship between CD1c + mDC alteration and disease progression has not yet been defined. EHI changes in CD1c + mDC counts, surface marker (CD40, CD86, CD83) expression, and IL-12 secretion were assessed by flow cytometry in 29 patients. When compared with the normal controls, patients with EHI displayed significantly lower CD1c + mDC counts and IL-12 secretion and increased surface markers. CD1c + mDC counts were positively correlated with CD4+ T cell counts and inversely associated with viral loads. IL-12 secretion was only positively associated with CD4+ T cell counts. Rapid progressors had lower counts, CD86 expression, and IL-12 secretion of CD1c + mDCs comparing with typical progressors. Kaplan-Meier analysis and Cox regression models suggested patients with low CD1c + mDC counts (<10 cells/μL) had a 4-fold higher risk of rapid disease progression than those with high CD1c + mDC counts. However, no relationship was found between surface markers or IL-12 secretion and disease progression. During EHI, patients with low CD1c + mDC counts were more likely to experience rapid disease progression than those with high CD1c + mDC counts.

Ageing and long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience.

PubMed

Wright, S T; Petoumenos, K; Boyd, M; Carr, A; Downing, S; O'Connor, C C; Grotowski, M; Law, M G

2013-04-01

The aim of this study was to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell count changes following the completion of 5 years of cART using linear mixed models. A total of 37 916 CD4 measurements were observed for 892 patients over a combined total of 9753 patient-years. Older patients (> 50 years old) at cART initiation had estimated mean (95% confidence interval) changes in CD4 counts by year-5 CD4 count strata (< 500, 500-750 and > 750 cells/μL) of 14 (7 to 21), 3 (-5 to 11) and -6 (-17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Our results suggest that duration of cART and increasing age do not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients, indicating that the level of immune recovery achieved during the first 5 years of treatment is sustained through long-term cART. © 2012 British HIV Association.

Ageing & long-term CD4 cell count trends in HIV-positive patients with 5 years or more combination antiretroviral therapy experience

PubMed Central

WRIGHT, ST; PETOUMENOS, K; BOYD, M; CARR, A; DOWNING, S; O’CONNOR, CC; GROTOWSKI, M; LAW, MG

2012-01-01

Background The aim of this analysis is to describe the long-term changes in CD4 cell counts beyond 5 years of combination antiretroviral therapy (cART). If natural ageing leads to a long-term decline in the immune system via low-grade chronic immune activation/inflammation, then one might expect to see a greater or earlier decline in CD4 counts in older HIV-positive patients with increasing duration of cART. Methods Retrospective and prospective data were examined from long-term virologically stable HIV-positive adults from the Australian HIV Observational Database. We estimated mean CD4 cell counts changes following the completion of 5 years of cART using linear mixed models. Results A total of 37,916 CD4 measurements were observed for 892 patients over a combined total of 9,753 patient years. Older patients (>50 years) at cART initiation had estimated mean(95% confidence interval) change in CD4 counts by Year-5 CD4 count strata (<500, 501–750 and >750 cells/μL) of 14(7 to 21), 3(−5 to 11) and −6(−17 to 4) cells/μL/year. Of the CD4 cell count rates of change estimated, none were indicative of long-term declines in CD4 cell counts. Conclusions Our results suggest that duration of cART and increasing age does not result in decreasing mean changes in CD4 cell counts for long-term virologically suppressed patients. Indicating that level of immune recovery achieved during the first 5 years of treatment are sustained through long-term cART. PMID:23036045

Reliable and Accurate CD4+ T Cell Count and Percent by the Portable Flow Cytometer CyFlow MiniPOC and “CD4 Easy Count Kit-Dry”, as Revealed by the Comparison with the Gold Standard Dual Platform Technology

PubMed Central

Nasi, Milena; De Biasi, Sara; Bianchini, Elena; Gibellini, Lara; Pinti, Marcello; Scacchetti, Tiziana; Trenti, Tommaso; Borghi, Vanni; Mussini, Cristina; Cossarizza, Andrea

2015-01-01

Background An accurate and affordable CD4+ T cells count is an essential tool in the fight against HIV/AIDS. Flow cytometry (FCM) is the “gold standard” for counting such cells, but this technique is expensive and requires sophisticated equipment, temperature-sensitive monoclonal antibodies (mAbs) and trained personnel. The lack of access to technical support and quality assurance programs thus limits the use of FCM in resource-constrained countries. We have tested the accuracy, the precision and the carry-over contamination of Partec CyFlow MiniPOC, a portable and economically affordable flow cytometer designed for CD4+ count and percentage, used along with the “CD4% Count Kit-Dry”. Materials and Methods Venous blood from 59 adult HIV+ patients (age: 25–58 years; 43 males and 16 females) was collected and stained with the “MiniPOC CD4% Count Kit-Dry”. CD4+ count and percentage were then determined in triplicate by the CyFlow MiniPOC. In parallel, CD4 count was performed using mAbs and a CyFlow Counter, or by a dual platform system (from Beckman Coulter) based upon Cytomic FC500 (“Cytostat tetrachrome kit” for mAbs) and Coulter HmX Hematology Analyzer (for absolute cell count). Results The accuracy of CyFlow MiniPOC against Cytomic FC500 showed a correlation coefficient (CC) of 0.98 and 0.97 for CD4+ count and percentage, respectively. The accuracy of CyFlow MiniPOC against CyFlow Counter showed a CC of 0.99 and 0.99 for CD4 T cell count and percentage, respectively. CyFlow MiniPOC showed an excellent repeatability: CD4+ cell count and percentage were analyzed on two instruments, with an intra-assay precision below ±5% deviation. Finally, there was no carry-over contamination for samples at all CD4 values, regardless of their position in the sequence of analysis. Conclusion The cost-effective CyFlow MiniPOC produces rapid, reliable and accurate results that are fully comparable with those from highly expensive dual platform systems. PMID:25622041

Differences of serum interleukin-6 levels in normotensive and preeclampsia women

NASA Astrophysics Data System (ADS)

Lumbanraja, S. N.; Junitasari, R.; Pasaribu, H. P.

2018-03-01

Red cell distribution width (RDW) has been shown higher with the increase of inflammatory activity. As CD4 count is not available in all cities in Indonesia, RDW was hoped to be the next promising marker to predict the progression of HIV infection. This study aims to find the association of RDW with aCD4 count in HIV-positive reproductive women in Indonesia. It was a prospective cross sectional study enrolled 37 consented outpatients HIV-positive reproductive women in Haji Adam Malik General Hospital, Medan, Indonesia. A 10 mL blood was taken, separated into two tubes for complete blood count and CD4 count. Data were collected and analyzed with SPSS 19.Mean CD4 absolute was lowest in >14.5% RDW group but without statistical significance. By classify CD4 absolute count, CD4 absolute ≤350/mm3 showed significantly higher RDW than CD4 absolute >350/mm3 (13.98±2.10% vs 12.79±0.88% p=0.02). No correlation was between RDW and CD4 absolute, as well as, with CD4%.In conclusion, high RDW can be a promising marker to predict the low CD4 count in HIV-positive reproductive women within antiretroviral therapy.

Association between depressive symptoms, CD4 count and HIV viral suppression among HIV-HCV co-infected people.

PubMed

Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Moodie, Erica E M; Anema, Aranka; Klein, Marina B; Brassard, Paul

2018-05-01

Depressive symptoms are associated with poor HIV viral control and immune recovery among people living with HIV. However, no prior studies assessed this association exclusively among people co-infected with HIV-hepatitis C virus (HCV). While people with HIV only and those with HIV-HCV co-infection share many characteristics, co-infected people may become more susceptible to the effects of depressive symptoms on health outcomes. We assessed this association exclusively among people co-infected with HIV-HCV in Canada using data from the Food Security & HIV-HCV Sub-Study (FS Sub-Study) of the Canadian Co-Infection Cohort (CCC). Stabilized inverse probability weighted marginal structural model was used to account for potential time-varying confounders. A total of 725 participants were enrolled between 2012 and 2015. At baseline, 52% of participants reported depressive symptoms, 75% had undetectable HIV viral load, and median CD4 count was 466 (IQR 300-665). People experiencing depressive symptoms had 1.32 times (95% CI: 1.07, 1.63) the risk of having detectable HIV viral load, but had comparable CD4 count to people who did not experience depressive symptoms (fold change of CD4 = 0.96, 95% CI: 0.91, 1.03). Presence of depressive symptoms is a risk factor for incomplete short-term HIV viral suppression among people co-infected with HIV-HCV. Therefore, depressive symptoms screening and related counseling may improve HIV related health outcomes and reduce HIV transmission.

Guidelines for prophylaxis of Pneumocystis pneumonia cannot rely solely on CD4-cell count in autoimmune and inflammatory diseases.

PubMed

Baulier, Gildas; Issa, Nahema; Gabriel, Frederic; Accoceberry, Isabelle; Camou, Fabrice; Duffau, Pierre

2018-02-26

Guidelines for preventing Pneumocystis pneumonia (PCP) in HIV patients are based on CD4 below 200/mm3. Such cut-off value is suggested to guide prophylaxis in non-HIV conditions (NHIV) especially in autoimmune and inflammatory diseases (AD). We aimed to determine if CD4 could be used to guide PCP prophylaxis in AD. CD4 and lymphocyte-count were retrospectively studied in patients diagnosed with PCP between January 2013 and February 2016. 129 patients were included. The median CD4-count was 302/mm3 in AD, which was significantly higher than in HIV patients (19/mm3; p<0.0001). Fifty percent (n=10) of AD patients had CD4 counts greater than 300/mm3. Prophylaxis for PCP cannot rely solely on CD4-count in NHIV patients especially in AD.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis.

PubMed

Ford, Nathan; Shubber, Zara; Jarvis, Joseph N; Chiller, Tom; Greene, Greg; Migone, Chantal; Vitoria, Marco; Doherty, Meg; Meintjes, Graeme

2018-03-04

Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL.

Task-shifting of CD4 T cell count monitoring by the touchscreen-based Muse™ Auto CD4/CD4% single-platform system for CD4 T cell numeration: Implication for decentralization in resource-constrained settings.

PubMed

Kouabosso, André; Mossoro-Kpinde, Christian Diamant; Bouassa, Ralph-Sydney Mboumba; Longo, Jean De Dieu; Mbeko Simaleko, Marcel; Grésenguet, Gérard; Bélec, Laurent

2018-04-01

The accuracy of CD4 T cell monitoring by the recently developed flow cytometry-based CD4 T cell counting Muse™ Auto CD4/CD4% Assay analyzer (EMD Millipore Corporation, Merck Life Sciences, KGaA, Darmstadt, Germany) was evaluated in trained lay providers against laboratory technicians. After 2 days of training on the Muse™ Auto CD4/CD4% analyzer, EDTA-blood samples from 6 HIV-positive and 4 HIV-negative individuals were used for CD4 T cell counting in triplicate in parallel by 12 trained lay providers as compared to 10 lab technicians. Mean number of CD4 T cells in absolute number was 829 ± 380 cells/μl by lay providers and 794 ± 409 cells/μl by technicians (P > 0.05); and in percentage 36.2 ± 14.8%CD4 by lay providers and 36.1 ± 15.0%CD4 by laboratory technician (P > 0.05). The unweighted linear regression and Passing-Bablok regression analyses on CD4 T cell results expressed in absolute count revealed moderate correlation between CD4 T cell counts obtained by lay providers and lab technicians. The mean absolute bias measured by Bland-Altman analysis between CD4 T cell/μl obtained by lay providers and lab technicians was -3.41 cells/μl. Intra-assay coefficient of variance (CV) of Muse™ Auto CD4/CD4% in absolute number was 10.1% by lay providers and 8.5% by lab technicians (P > 0.05), and in percentage 5.5% by lay providers and 4.4% by lab technicians (P > 0.05). The inter-assay CV of Muse™ Auto CD4/CD4% in absolute number was 13.4% by lay providers and 10.3% by lab technicians (P > 0.05), and in percentage 7.8% by lay providers and 6.9% by lab technicians (P > 0.05). The study demonstrates the feasibility of CD4 T cell counting using the alternative flow cytometer Muse™ Auto CD4/CD4% analyzer by trained lay providers and therefore the practical possibility of decentralization CD4 T cell counting to health community centers. Copyright © 2018. Published by Elsevier B.V.

CD4 Lymphocyte Count: MedlinePlus Lab Test Information

MedlinePlus

... Clinics Authority; c2017. CD4+ Count Results [updated 2017 Mar 3; cited 2017 Nov 29]; [about 7 screens]. ... Authority; c2017. CD4+ Count Test Overview [updated 2017 Mar 3; cited 2017 Nov 29]; [about 2 screens]. ...

The role of CD4 cell count as discriminatory measure to guide chemoprophylaxis against Pneumocystis jirovecii pneumonia in human immunodeficiency virus-negative immunocompromised patients: A systematic review.

PubMed

Messiaen, Peter E; Cuyx, Senne; Dejagere, Tom; van der Hilst, Jeroen C

2017-04-01

In recent years, the incidence of Pneumocystis jirovecii pneumonia (PJP) has increased in immunocompromised patients without human immunodeficiency virus (HIV) infection. Chemoprophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX) is highly effective in preventing PJP in both HIV-positive and -seronegative patients. In HIV-positive patients, the risk of PJP is strongly correlated with decreased CD4 cell count. The role of CD4 cell count in the pathogenesis of PJP in non-HIV immunocompromised patients is less well studied. For most immunosuppressive conditions, no clear guidelines indicate whether to start TMP-SMX. We conducted a systematic literature review with the aim to provide a comprehensive overview on the role of CD4 cell counts in managing the risk of PJP in HIV-seronegative patients. Of the 63 individual studies retrieved, 14 studies report on CD4 cell counts in a variety of immunosuppressive conditions. CD4 cell count were <200/μL in 73.1% of the patients. CD4 cell count <200/μL is a sensitive biomarker to identify non-HIV immunocompromised patients who are at risk for PJP. Measuring CD4 cell counts could help clinicians identify patients who may benefit from TMP-SMX prophylaxis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Safety, Pharmacokinetics and Efficacy of Dolutegravir in Treatment-experienced HIV-1 Infected Adolescents: Forty-eight-week Results from IMPAACT P1093.

PubMed

Viani, Rolando M; Alvero, Carmelita; Fenton, Terry; Acosta, Edward P; Hazra, Rohan; Townley, Ellen; Steimers, Debra; Min, Sherene; Wiznia, Andrew

2015-11-01

To assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents. Children older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0 mg/kg once daily in a phase I/II multicenter open label 48-week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption. Safety and HIV RNA and CD4 cell count assessments were performed through week 48. Twenty-three adolescents were enrolled and 22 (96%) completed the 48-week study visit. Median age and weight were 15 years and 52 kg, respectively. Median [interquartile range (IQR)] baseline CD4+ cell count was 466 cells/μL (297, 771). Median (IQR) baseline HIV-1 RNA log10 was 4.3 log10 copies/mL (3.9, 4.6). Dolutegravir geometric mean of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing (AUC0-24) and 24 hour postdose concentration (C24) were 46.0 μg hours/mL and 0.90 μg/mL, respectively, which were within the study targets based on adult PK ranges. Virologic success with an HIV RNA <400 copies/mL was achieved in 74% [95% confidence interval (CI): 52-90%] at week 48. Additionally, 61% (95% CI: 39-80%) had an HIV RNA <50 copies/mL at week 48. Median (IQR) gain in CD4 cell count at week 48 was 84 cells/μL (-81, 238). Dolutegravir was well tolerated, with no grade 4 adverse events, serious adverse events or discontinuations because of serious adverse events. Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.

Predictors of anaemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections

PubMed Central

Finkelstein, Julia L; Mehta, Saurabh; Duggan, Christopher P; Spiegelman, Donna; Aboud, Said; Kupka, Roland; Msamanga, Gernard I; Fawzi, Wafaie W

2012-01-01

Objective Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania. Design Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period. Setting Antenatal clinics in Dar es Salaam, Tanzania. Subjects Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995–1997). Results Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1·4 and 2·3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period. Conclusions Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings – particularly during the pre- and postpartum periods. PMID:22014374

Predictors of anaemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections.

PubMed

Finkelstein, Julia L; Mehta, Saurabh; Duggan, Christopher P; Spiegelman, Donna; Aboud, Said; Kupka, Roland; Msamanga, Gernard I; Fawzi, Wafaie W

2012-05-01

Anaemia is common during pregnancy, and prenatal Fe supplementation is the standard of care. However, the persistence of anaemia despite Fe supplementation, particularly in HIV infection, suggests that its aetiology may be more complex and warrants further investigation. The present study was conducted to examine predictors of incident haematological outcomes in HIV-infected pregnant women in Tanzania. Prospective cohort study. Cox proportional hazards and binomial regression models were used to identify predictors of incident haematological outcomes: anaemia (Hb < 110 g/l), severe anaemia (Hb < 85 g/l) and hypochromic microcytosis, during the follow-up period. Antenatal clinics in Dar es Salaam, Tanzania. Participants were 904 HIV-infected pregnant women enrolled in a randomized trial of vitamins (1995-1997). Malaria, pathogenic protozoan and hookworm infections at baseline were associated with a two-fold increase in the risk of anaemia and hypochromic microcytosis during follow-up. Higher baseline erythrocyte sedimentation rate and CD8 T-cell concentrations, and lower Hb concentrations and CD4 T-cell counts, were independent predictors of incident anaemia and Fe deficiency. Low baseline vitamin D (<32 ng/ml) concentrations predicted a 1.4 and 2.3 times greater risk of severe anaemia and hypochromic microcytosis, respectively, during the follow-up period. Parasitic infections, vitamin D insufficiency, low CD4 T-cell count and high erythrocyte sedimentation rate were the main predictors of anaemia and Fe deficiency in pregnancy and the postpartum period in this population. A comprehensive approach to prevent and manage anaemia, including micronutrient supplementation and infectious disease control, is warranted in HIV-infected women in resource-limited settings - particularly during the pre- and postpartum periods.

Correlation of CD4 counts with microalbuminuria in HIV patients

NASA Astrophysics Data System (ADS)

Bakri, S.; Haerani, R.; Hasyim, K.; Sudirman, K.; Tarukallo, N.

2018-03-01

One of the manifestations of kidney disease is Microalbuminuria (MA). CD4 T cells are cells that play a central role in immune protection, wherein HIV infections, they are the primary target of the virus. CD4 cells counts is an indirect reflection of the activity and viral load of HIV. This study aimed to determine the correlation of CD4 counts with MA in HIV patients. A cross-sectional with thedescriptive analytical study was in HIV patients >18 years old without a history of Diabetes Mellitus. The result of thestatistical test is significant if the value of p <0.05. The prevalence of MA in subjects with CD4 cell counts <200 cells/μl was 56.1%, and NA was 43.9%. On the other hand, in subjects with CD4 ≥ 200 cells/μl, the prevalence of MA was 3.4% and the prevalence of NA was 96%. In conclusion, there was a significant correlation of low count CD4 (CD4 <200 cells/μl) with microalbuminuria in HIV patients.

High CD4 counts associated with better economic outcomes for HIV-positive adults and their HIV-negative household members in the SEARCH Trial.

PubMed

Jakubowski, Aleksandra; Snyman, Katherine; Kwarisiima, Dalsone; Sang, Norton; Burger, Rachel; Balzer, Laura; Clark, Tamara; Chamie, Gabriel; Shade, Starley; Cohen, Craig; Bukusi, Elizabeth; Charlebois, Edwin; Kamya, Moses; Petersen, Maya; Havlir, Diane; Thirumurthy, Harsha

2018-01-01

Country decisions to scale-up "test and treat" approaches for HIV depend on consideration of both the health and economic consequences of such investments. Evidence about economic impacts of expanded antiretroviral therapy (ART) provision is particularly relevant for decisions regarding foreign assistance levels for HIV/AIDS programs. We used baseline data from the Sustainable East Africa Research in Community Health (SEARCH) cluster randomized controlled trial in Kenya and Uganda to examine the association between HIV status, CD4+ T-cell counts, viral suppression, and multiple indicators of economic well-being. Socio-economic surveys were conducted in households with HIV-positive and HIV-negative adults sampled after a census of 32 communities participating in the SEARCH trial (NCT01864603). Data were obtained for 11,500 individuals from 5,884 households in study communities. Participants were stratified based on their own HIV status as well as CD4 counts and viral suppression status if they were HIV-positive. HIV-negative participants residing in households with no HIV-positive adults were considered separately from HIV-negative participants residing in households with ≥1 HIV-positive adult. Generalized estimating equation models were used to examine the relationship between HIV status, CD4 counts, ART, viral suppression, and outcomes of employment, self-reported illness, lost time from usual activities due to illness, healthcare utilization, health expenditures, and hospitalizations. In all models, HIV-negative participants in households with no HIV-positive persons were the reference group. There was no significant difference in the probability of being employed between HIV-positive participants with CD4>500 and the reference group of HIV-negative participants residing in households with no HIV-positive adults (marginal effect, ME, 1.49 percentage points; 95% confidence interval, CI, -1.09, 4.08). However, HIV-positive participants with CD4 351-500 were less likely to be employed than the reference group (ME -4.50, 95% CI -7.99, -1.01), as were HIV-positive participants with CD4 ≤350 (ME -7.41, 95% CI -10.96, -3.85). Similarly, there was no significant difference in employment likelihood between HIV-negative participants who resided in households with a CD4>500 HIV-positive person and the reference group (ME -1.78, 95% CI -5.16, 1.59). HIV-negative participants residing with an HIV-positive person with CD4 351-500, however, were less likely to be employed than the reference group (ME -7.03, 95% CI -11.49, -2.57), as were people residing with a household member with CD4 ≤350 (ME -6.28, 95% CI -10.76, -1.80). HIV-positive participants in all CD4 categories were more likely to have lost time from usual activities due to illness and have incurred healthcare expenditures. Those with CD4>500 had better economic outcomes than those with CD4 351-500, even among those not virally suppressed (p = 0.004) and not on ART (p = 0.01). Data from a large population-representative sample of households in east Africa showed a strong association between the health of HIV-positive persons and economic outcomes. The findings suggest there may be economic benefits associated with maintaining high CD4 counts, both for HIV-positive persons and their HIV-negative household members. The association of high CD4 counts with improved outcomes is consistent with the hypothesis that early ART initiation can avert declines in employment and other economic outcomes. Prospective longitudinal evaluation is needed to assess the causal impact of early ART initiation on economic functioning of households.

Food insecurity and low CD4 count among HIV-infected people: a systematic review and meta-analysis.

PubMed

Aibibula, Wusiman; Cox, Joseph; Hamelin, Anne-Marie; Mamiya, Hiroshi; Klein, Marina B; Brassard, Paul

2016-12-01

Food insecurity is defined as a limited or uncertain ability to acquire acceptable foods in socially acceptable ways, or limited or uncertain availability of nutritionally adequate and safe foods. While effective antiretroviral treatment can significantly increase CD4 counts in the majority of patients, there are certain populations who remain at relatively low CD4 count levels. Factors possibly associated with poor CD4 recovery have been extensively studied, but the association between food insecurity and low CD4 count is inconsistent in the literature. The objective is to systematically review published literature to determine the association between food insecurity and CD4 count among HIV-infected people. PubMed, Web of Science, ProQuest ABI/INFORM Complete, Ovid Medline and EMBASE Classic, plus bibliographies of relevant studies were systematically searched up to May 2015, where the earliest database coverage started from 1900. Studies that quantitatively assessed the association between food insecurity and CD4 count among HIV-infected people were eligible for inclusion. Study results were summarized using random effects model. A total of 2093 articles were identified through electronic database search and manual bibliographic search, of which 8 studies included in this meta-analysis. Food insecure people had 1.32 times greater odds of having lower CD4 counts compared to food secure people (OR = 1.32, 95% CI: 1.15-1.53) and food insecure people had on average 91 fewer CD4 cells/µl compared to their food secure counterparts (mean difference = -91.09, 95% CI: -156.16, -26.02). Food insecurity could be a potential barrier to immune recovery as measured by CD4 counts among HIV-infected people.

Hierarchy Low CD4+/CD8+ T-Cell Counts and IFN-γ Responses in HIV-1+ Individuals Correlate with Active TB and/or M.tb Co-Infection.

PubMed

Shao, Lingyun; Zhang, Xinyun; Gao, Yan; Xu, Yunya; Zhang, Shu; Yu, Shenglei; Weng, Xinhua; Shen, Hongbo; Chen, Zheng W; Jiang, Weimin; Zhang, Wenhong

2016-01-01

Detailed studies of correlation between HIV-M.tb co-infection and hierarchy declines of CD8+/CD4+ T-cell counts and IFN-γ responses have not been done. We conducted case-control studies to address this issue. 164 HIV-1-infected individuals comprised of HIV-1+ATB, HIV-1+LTB and HIV-1+TB- groups were evaluated. Immune phenotyping and complete blood count (CBC) were employed to measure CD4+ and CD8+ T-cell counts; T.SPOT.TB and intracellular cytokine staining (ICS) were utilized to detect ESAT6, CFP10 or PPD-specific IFN-γ responses. There were significant differences in median CD4+ T-cell counts between HIV-1+ATB (164/μL), HIV-1+LTB (447/μL) and HIV-1+TB- (329/μL) groups. Hierarchy low CD4+ T-cell counts (<200/μL, 200-500/μL, >500/μL) were correlated significantly with active TB but not M.tb co-infection. Interestingly, hierarchy low CD8+ T-cell counts were not only associated significantly with active TB but also with M.tb co-infection (P<0.001). Immunologically, HIV-1+ATB group showed significantly lower numbers of ESAT-6-/CFP-10-specific IFN-γ+ T cells than HIV-1+LTB group. Consistently, PPD-specific IFN-γ+CD4+/CD8+ T effector cells in HIV-1+ATB group were significantly lower than those in HIV-1+LTB group (P<0.001). Hierarchy low CD8+ T-cell counts and effector function in HIV-1-infected individuals are correlated with both M.tb co-infection and active TB. Hierarchy low CD4+ T-cell counts and Th1 effector function in HIV-1+ individuals are associated with increased frequencies of active TB, but not M.tb co-infection.

Death rates in HIV-positive antiretroviral-naive patients with CD4 count greater than 350 cells per microL in Europe and North America: a pooled cohort observational study

PubMed Central

2011-01-01

Background It is unclear whether antiretroviral (ART) naive HIV-positive individuals with high CD4 counts have a raised mortality risk compared with the general population, but this is relevant for considering earlier initiation of antiretroviral therapy. Methods Pooling data from 23 European and North American cohorts, we calculated country-, age-, sex-, and year-standardised mortality ratios (SMRs), stratifying by risk group. Included patients had at least one pre-ART CD4 count above 350 cells/mm3. The association between CD4 count and death rate was evaluated using Poisson regression methods. Findings Of 40,830 patients contributing 80,682 person-years of follow up with CD4 count above 350 cells/mm3, 419 (1.0%) died. The SMRs (95% confidence interval) were 1.30 (1.06-1.58) in homosexual men, and 2.94 (2.28-3.73) and 9.37 (8.13-10.75) in the heterosexual and IDU risk groups respectively. CD4 count above 500 cells/mm3 was associated with a lower death rate than 350-499 cells/mm3: adjusted rate ratios (95% confidence intervals) for 500-699 cells/mm3 and above 700 cells/mm3 were 0.77 (0.61-0.95) and 0.66 (0.52-0.85) respectively. Interpretation In HIV-infected ART-naive patients with high CD4 counts, death rates were raised compared with the general population. In homosexual men this was modest, suggesting that a proportion of the increased risk in other groups is due to confounding by other factors. Even in this high CD4 count range, lower CD4 count was associated with raised mortality. PMID:20638118

HIV-1 disease progression during highly active antiretroviral therapy: an application using population-level data in British Columbia: 1996-2011.

PubMed

Nosyk, Bohdan; Min, Jeong; Lima, Viviane D; Yip, Benita; Hogg, Robert S; Montaner, Julio S G

2013-08-15

Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011. We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ≥ 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period. A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively. Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.

CD4 count-based failure criteria combined with viral load monitoring may trigger worse switch decisions than viral load monitoring alone.

PubMed

Hoffmann, Christopher J; Maritz, Jean; van Zyl, Gert U

2016-02-01

CD4 count decline often triggers antiretroviral regimen switches in resource-limited settings, even when viral load testing is available. We therefore compared CD4 failure and CD4 trends in patients with viraemia with or without antiretroviral resistance. Retrospective cohort study investigating the association of HIV drug resistance with CD4 failure or CD4 trends in patients on first-line antiretroviral regimens during viraemia. Patients with viraemia (HIV RNA >1000 copies/ml) from two HIV treatment programmes in South Africa (n = 350) were included. We investigated the association of M184V and NNRTI resistance with WHO immunological failure criteria and CD4 count trends, using chi-square tests and linear mixed models. Fewer patients with the M184V mutation reached immunologic failure criteria than those without: 51 of 151(34%) vs. 90 of 199 (45%) (P = 0.03). Similarly, 79 of 220 (36%) patients, who had major NNRTI resistance, had immunological failure, whereas 62 of 130 (48%) without (chi-square P = 0.03) did. The CD4 count decline among patients with the M184V mutation was 2.5 cells/mm(3) /year, whereas in those without M184V it was 14 cells/mm(3) /year (P = 0.1), but the difference in CD4 count decline with and without NNRTI resistance was marginal. Our data suggest that CD4 count monitoring may lead to inappropriate delayed therapy switches for patients with HIV drug resistance. Conversely, patients with viraemia but no drug resistance are more likely to have a CD4 count decline and thus may be more likely to be switched to a second-line regimen. © 2015 John Wiley & Sons Ltd.

CDC staging based on absolute CD4 count and CD4 percentage in an HIV-1-infected Indian population: treatment implications

PubMed Central

Vajpayee, M; Kaushik, S; Sreenivas, V; Wig, N; Seth, P

2005-01-01

CD4+ T-cell levels are an important criterion for categorizing HIV-related clinical conditions according to the CDC classification system and are therefore important in the management of HIV by initiating antiretroviral therapy and prophylaxis for opportunistic infections due to HIV among HIV-infected individuals. However, it has been observed that the CD4 counts are affected by the geographical location, race, ethnic origin, age, gender and changes in total and differential leucocyte counts. In the light of this knowledge, we classified 600 HIV seropositive antiretroviral treatment (ART)-naïve Indian individuals belonging to different CDC groups A, B and C on the basis of CDC criteria of both CD4% and CD4 counts and receiver operating characteristic (ROC) curves were generated. Importantly, CDC staging on the basis of CD4% indicated significant clinical implications, requiring an early implementation of effective antiretroviral treatment regimen in HIV-infected individuals deprived of treatment when classified on the basis of CD4 counts. PMID:16045738

Graded versus Intermittent Exercise Effects on Lymphocytes in Chronic Fatigue Syndrome.

PubMed

Broadbent, Suzanne; Coutts, Rosanne

2016-09-01

There is increasing evidence of immune system dysfunction in chronic fatigue syndrome (CFS), but little is known of the regular exercise effects on immune cell parameters. This pilot study investigated the effects of graded and intermittent exercise on CD4 lymphocyte subset counts and activation compared with usual care. Twenty-four CFS patients (50.2 ± 10 yr) were randomized to graded exercise (GE), intermittent exercise (IE), or usual care (UC) groups; 18 sedentary non-CFS participants (50.6 ± 10 yr) were controls (CTL) for blood and immunological comparisons. Outcome measures were pre- and postintervention flow cytometric analyses of circulating lymphocyte subset cell counts; expression of CD3, CD4, CD25, and CD134; full blood counts; and V˙O2peak. Preintervention, CD3 cell counts, and expression of CD4, CD25, CD134, and CD4CD25CD134 were significantly lower in GE, IE, and UC compared with CTL (P < 0.05). Total lymphocyte concentration was significantly lower in GE and IE groups compared with CTL. There were significant postintervention increases in i) expression of CD4 and CD4CD25CD134 for GE and IE, but CD25 and CD134 for IE only; ii) circulating counts of CD3 and CD4 for GE, and CD3, CD4, CD8, CD3CD4CD8, CD3CD16CD56, CD19, and CD45 for IE; iii) neutrophil concentration for GE; and iv) V˙O2peak and elapsed test time for IE and GE, V˙Epeak for IE. Twelve weeks of GE and IE training significantly improved CD4 lymphocyte activation and aerobic capacity without exacerbating CFS symptoms. IE may be a more effective exercise modality with regard to enhanced CD4 activation in CFS patients.

Correlates of preserved CD4(+) T cell homeostasis during natural, nonpathogenic simian immunodeficiency virus infection of sooty mangabeys: implications for AIDS pathogenesis.

PubMed

Sumpter, Beth; Dunham, Richard; Gordon, Shari; Engram, Jessica; Hennessy, Margaret; Kinter, Audrey; Paiardini, Mirko; Cervasi, Barbara; Klatt, Nichole; McClure, Harold; Milush, Jeffrey M; Staprans, Silvija; Sodora, Donald L; Silvestri, Guido

2007-02-01

In contrast to HIV-infected humans, naturally SIV-infected sooty mangabeys (SMs) very rarely progress to AIDS. Although the mechanisms underlying this disease resistance are unknown, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To define the correlates of preserved CD4(+) T cell counts in SMs, we conducted a cross-sectional immunological study of 110 naturally SIV-infected SMs. The nonpathogenic nature of the infection was confirmed by an average CD4(+) T cell count of 1,076 +/- 589/mm(3) despite chronic infection with a highly replicating virus. No correlation was found between CD4(+) T cell counts and either age (used as a surrogate marker for length of infection) or viremia. The strongest correlates of preserved CD4(+) T cell counts were a low percentage of circulating effector T cells (CD28(-)CD95(+) and/or IL-7R/CD127(-)) and a high percentage of CD4(+)CD25(+) T cells. These findings support the hypothesis that the level of immune activation is a key determinant of CD4(+) T cell counts in SIV-infected SMs. Interestingly, we identified 14 animals with CD4(+) T cell counts of <500/mm(3), of which two show severe and persistent CD4(+) T cell depletion (<50/mm(3)). Thus, significant CD4(+) T cell depletion does occasionally follow SIV infection of SMs even in the context of generally low levels of immune activation, lending support to the hypothesis of multifactorial control of CD4(+) T cell homeostasis in this model of infection. The absence of AIDS in these "CD4(low)" naturally SIV-infected SMs defines a protective role of the reduced immune activation even in the context of a significant CD4(+) T cell depletion.

API consensus guidelines for use of antiretroviral therapy in adults (API-ART guidelines). Endorsed by the AIDS Society of India.

PubMed

Gupta, S B; Pujari, S N; Joshi, S R; Patel, A K

2006-01-01

With rational use of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection has been transformed into a chronic manageable illness like diabetes and hypertension. These guidelines provide information on state of art, evidence based approach for use of ART in Indian context. When to initiate ART? Antiretroviral therapy is indicated for all symptomatic HIV infected persons regardless of CD4 counts and plasma viral load (PVL) levels. In asymptomatic patients, ART should be offered when the CD4 counts < 200/mm3 and should be considered in patients with CD4 counts between 200-250/mm3. Therapy is not recommended for patients with CD4 count more than 350/ mm3. Involvement of patient in all treatment decisions and assessing readiness is critical before initiating ART. What to start with? A non-nucleoside reverse transcriptase inhibitor (NNRTI) based regimen is recommended for antiretroviral naïve patients. The choice between nevirapine and efavirenz is based on differences in adverse events profiles; cost and availability of convenient fixed dose combinations and need for concomitant use of rifampicin. A backbone of 2-nucleoside reverse transcriptase inhibitors (NRTIs) is combined with the NNRTI. Various combinations and ART strategies not to be used in clinical practice has been enlisted. How to follow up? Recommendations have been made for baseline evaluation and monitoring of patients on ART. These include guidelines on laboratory and clinical evaluation. A plasma viral load at 6 months after initiation of first-line ART is strongly recommended. Yearly estimation of lipid profile has been recommended. How to identify and manage ART failure? The guidelines recognize the issue of identifying ART failure late if only CD4 counts are used for monitoring. In the absence of resistance testing various second-line regimens have been enlisted. A boosted protease inhibitor based regimen is recommended in this situation to be combined with 2-NRTIs. Special situations Recommendations have been made for use of ART in HIV-TB, HIV-HBV, and HIV-HCV co-infected patients. In patients with active TB and a CD4 count < 200/mm3, initiation of ART is recommended as soon as the anti-TB treatment is tolerated. Efavirenz is the only ARV drug, which can be safely used with rifampicin. In pregnancy use of single dose nevirapine for reducing risk of mother to child transmission of HIV is not recommended, because of the risk of development of resistance. For post-exposure prophylaxis taking ART treatment history of the source patient is crucial in designing an effective regimen.

Analysis cluster of differentiation 4 number and c-reactive protein concentration in patient with human immunodeficiency virus with or without lung tuberculosis

NASA Astrophysics Data System (ADS)

Nur, M. J.; Kuhuwael, F.; Katu, S.; Mubin, H.; Halim, R.

2018-03-01

HIV infected patients characterized by decrease CD4 cell count, where lower CD4 count, has higher infection risk. In HIV patients with Lung, Tuberculosis co-infection showed increase CRP level concomitant with disease severity. This study attempts to analyze TB incidence in HIV cases by looking at CD4 cell count and CRP levels in HIV-infected subjects. For analyzing the CD4 cell count and CRP levels in HIV patient with and without Lung Tuberculosis co-infection in Wahidin Sudirohusodo Hospital. Conducted observational study with cross-sectional design on HIV subjects withand without Lung Tuberculosis co-infection in Wahidin Sudirohusodo Hospital from September 2016 to June 2017. Patients divided into HIV group without TB co-infection, and with TB co-infection. Each group will be assessed CRP levels, which considered low <5 mg/L and high >5 mg/L, whereas CD4 cell count, considered low <200 cell/mm3 and normal >200 cell/mm3. Results are considered significant if p-value<0.05. There were a significantly higher CRP levels (p<0.02) and lower CD4 counts (p<0.02) in HIV with TB co-infection and no significant relationship between CRP levels with aCD4 count in both groups.

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis

PubMed Central

Ford, Nathan; Shubber, Zara; Jarvis, Joseph N; Chiller, Tom; Greene, Greg; Migone, Chantal; Vitoria, Marco; Doherty, Meg; Meintjes, Graeme

2018-01-01

Abstract Background Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%–7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%–2.7%; 21 studies) among patients with CD4 count 101–200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%–22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101–200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%–15.5%]) compared with outpatients (6.3% [95% CI, 5.3%–7.4%]). Conclusions The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL. PMID:29514236

Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

PubMed

Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

2013-11-01

It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P < 0.0001). Only patients starting HAART with CD4 counts >350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

Analysis of HIV disease burden by calculating the percentages of patients with CD4 counts <100 cells/µL across 52 districts reveals hot spots for intensified commitment to programmatic support.

PubMed

Coetzee, Lindi Marie; Cassim, Naseem; Glencross, Deborah Kim

2017-05-24

South Africa (SA)'s Comprehensive HIV and AIDS Care, Management and Treatment (CCMT) programme has reduced new HIV infections and HIV-related deaths. In spite of progress made, 11.2% of South Africans (4.02 million) were living with HIV in 2015. The National Health Laboratory Service (NHLS) in SA performs CD4 testing in support of the CCMT programme and collates data through the NHLS Corporate Data Warehouse. The objective of this study was to assess the distribution of CD4 counts <100 cells/µL (defining severely immunosuppressed HIV-positive patients) and >500 cells/µL (as an HIV-positive 'wellness' indicator). CD4 data were extracted for the financial years 2010/11 and 2014/15, according to the district where the test was ordered, for predefined CD4 ranges. National and provincial averages of CD4 counts <100 and >500 cells/µL were calculated. Data were analysed using Stata 12 and mapping was done with ArcGIS software, reporting percentages of CD4 counts <100 and >500 cells/µL by district. The national average percentage of patients with CD4 counts <100 cells/µL showed a marked decrease (by 22%) over the 5-year study period, with a concurrent increase in CD4 counts >500 cells/µL (by 57%). District-by-district analysis showed that in 2010/11, 44/52 districts had >10% of CD4 samples with counts <100 cells/µL, decreasing to only 17/52 districts by 2014/15. Overall, districts in the Western Cape and KwaZulu-Natal had the lowest percentages of CD4 counts <100 cells/µL, as well as the highest percentages of counts >500 cells/µL. In contrast, in 2014/15, the highest percentages of CD4 counts <100 cells/µL were noted in the West Rand (Gauteng), Vhembe (Limpopo) and Nelson Mandela Bay (Eastern Cape) districts, where the lowest percentages of counts >500 cells/µL were also noted. The percentages of CD4 counts <100 cells/µL highlighted here reveal districts with positive change suggestive of programmatic improvements, and also highlight districts requiring local interventions to achieve the UNAIDS/SA National Department of Health 90-90-90 HIV treatment goals. The study further underscores the value of using NHLS laboratory data, an underutilised national resource, to leverage laboratory test data to enable a more comprehensive understanding of programme-specific health indicators.

The evolving role of CD4 cell counts in HIV care.

PubMed

Ford, Nathan; Meintjes, Graeme; Vitoria, Marco; Greene, Greg; Chiller, Tom

2017-03-01

The role of the CD4 cell count in the management of people living with HIV is once again changing, most notably with a shift away from using CD4 assays to decide when to start antiretroviral therapy (ART). This article reflects on the past, current and future role of CD4 cell count testing in HIV programmes, and the implications for clinicians, programme managers and diagnostics manufacturers. Following the results of recent randomized trials demonstrating the clinical and public health benefits of starting ART as soon as possible after HIV diagnosis is confirmed, CD4 cell count is no longer recommended as a way to decide when to initiate ART. For patients stable on ART, CD4 cell counts are no longer needed to monitor the response to treatment where HIV viral load testing is available. Nevertheless CD4 remains the best measurement of a patient's immune and clinical status, the risk of opportunistic infections, and supports diagnostic decision-making, particularly for patients with advanced HIV disease. As countries revise guidelines to provide ART to all people living with HIV and continue to scale up access to viral load, strategic choices will need to be made regarding future investments in CD4 cell count and the appropriate use for clinical disease management.

HIV DNA in CD14+ reservoirs is associated with regional brain atrophy in patients naive to combination antiretroviral therapy.

PubMed

Kallianpur, Kalpana J; Valcour, Victor G; Lerdlum, Sukalaya; Busovaca, Edgar; Agsalda, Melissa; Sithinamsuwan, Pasiri; Chalermchai, Thep; Fletcher, James L K; Tipsuk, Somporn; Shikuma, Cecilia M; Shiramizu, Bruce T; Ananworanich, Jintanat

2014-07-17

To examine associations between regional brain volumes and HIV DNA in peripheral CD14 cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART). A prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrolment was stratified by HIV DNA in a blinded fashion. CD14 cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla MRI were compared between HIV DNA groups using analysis of covariance (ANCOVA). We studied 60 individuals with mean (SD) age of 34.7 (7.0) years, CD4 T-lymphocyte count of 232 (137) cells/μl and log10 plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 10 CD14 cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/10 cells for this cohort, a threshold value above which CD14 HIV DNA identified HIV-associated neurocognitive disorders (HANDs), we found that CD14 HIV DNA  ≥ 45 copies/10 cells was associated with reduced volumes of the nucleus accumbens (P=0.021), brainstem (P=0.033) and total gray matter (P=0.045) independently of age, CD4 cell count and intracranial volume. HIV DNA burden in CD14 monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells.

Risk factors for Kaposi's sarcoma in human immunodeficiency virus patients after initiation of antiretroviral therapy: A nested case-control study in Kenya.

PubMed

Lupia, Rodgers; Wabuyia, Peter B; Otiato, Peter; Fang, Chi-Tai; Tsai, Feng-Jen

2017-12-01

This study aimed to evaluate the association between highly active antiretroviral therapy (HAART) adherence and development of Kaposi's sarcoma (KS) in human immunodeficiency virus (HIV)/AIDS patients. We conducted a retrospective nested case-control study of 165 participants (33 cases and 132 controls) receiving HAART care at Maseno Hospital, Kenya, from January 2005 to October 2013. Cases were HIV-positive adults with KS, who were matched with controls in a ratio of 1:4 based on age (±5 years of each case), sex, and KS diagnosis date. Perfect adherence to HAART was assessed on every clinic visit by patients' self-reporting and pill counts. Chi-square tests were performed to compare socioeconomic and clinical statuses between cases and controls. A conditional logistic regression was used to assess the effects of perfect adherence to HAART, the latest CD4 count, education level, distance to health-care facility, initial World Health Organization stage, and number of regular sexual partners on the development of KS. Only 63.6% participants reported perfect adherence, and the control group had a significantly higher percentage of perfect adherence (75.0%) than did cases (18.2%). After adjustment for potential imbalances in the baseline and clinical characteristics, patients with imperfect HAART adherence had 20-times greater risk of developing KS than patients with perfect HAART adherence [hazard ratios: 21.0, 95% confidence interval: 4.2-105.1]. Patients with low latest CD4 count (≤350 cells/mm 3 ) had a seven-times greater risk of developing KS than did their counterparts (HRs: 7.1, 95% CI: 1.4-36.2). Imperfect HAART adherence and low latest CD4 count are significantly associated with KS development. Copyright © 2015. Published by Elsevier B.V.

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study

PubMed Central

2011-01-01

Background Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. Methods A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrolment. Results Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. Conclusions Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population. PMID:21251265

Genital warts and infection with human immunodeficiency virus in high-risk women in Burkina Faso: a longitudinal study.

PubMed

Low, Andrea J; Clayton, Tim; Konate, Issouf; Nagot, Nicolas; Ouedraogo, Abdoulaye; Huet, Charlotte; Didelot-Rousseau, Marie-Noelle; Segondy, Michel; Van de Perre, Philippe; Mayaud, Philippe

2011-01-20

Human papillomaviruses are the most common sexually transmitted infections, and genital warts, caused by HPV-6 and 11, entail considerable morbidity and cost. The natural history of genital warts in relation to HIV-1 infection has not been described in African women. We examined risk factors for genital warts in a cohort of high-risk women in Burkina Faso, in order to further describe their epidemiology. A prospective study of 765 high-risk women who were followed at 4-monthly intervals for 27 months in Burkina Faso. Logistic and Cox regression were used to identify factors associated with prevalent, incident and persistent genital warts, including HIV-1 serostatus, CD4+ count, and concurrent sexually transmitted infections. In a subset of 306 women, cervical HPV DNA was tested at enrollment. Genital wart prevalence at baseline was 1.6% (8/492) among HIV-uninfected and 7.0% (19/273) among HIV-1 seropositive women. Forty women (5.2%) experienced at least one incident GW episode. Incidence was 1.1 per 100 person-years among HIV-uninfected women, 7.4 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count >200 cells/μL and 14.6 per 100 person-years among HIV-1 seropositive women with a nadir CD4+ count ≤ 200 cells/μL. Incident genital warts were also associated with concurrent bacterial vaginosis, and genital ulceration. Antiretroviral therapy was not protective against incident or persistent genital warts. Detection of HPV-6 DNA and abnormal cervical cytology were strongly associated with incident genital warts. Genital warts occur much more frequently among HIV-1 infected women in Africa, particularly among those with low CD4+ counts. Antiretroviral therapy did not reduce the incidence or persistence of genital warts in this population.

Practices to improve identification of Adult Antiretroviral Therapy failure at the Lighthouse Trust clinic in Lilongwe, Malawi

PubMed Central

Vorkas, Charles Kyriakos; Tweya, Hannock; Mzinganjira, Dalitso; Dickie, George; Weigel, Ralf; Phiri, Sam; Hosseinipour, Mina C.

2011-01-01

Summary Background Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status. Methods Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count 50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from 12/2007–12/2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher’s exact tests and unpaired t-tests as appropriate. Results Of 7,000 enrolled ART patients ≥ 15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow-up time on ART of 1.4 years (IQR: 0.8–2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and 1 (7%) patient was switched to second-line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (p<0.0001; 95% CI 0.03–0.08). Conclusions Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed. PMID:22039960

Metal ion levels and lymphocyte counts: ASR hip resurfacing prosthesis vs. standard THA

PubMed Central

2013-01-01

Background and purpose Wear particles from metal–on–metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above–average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA) and investigated whether cobalt and chromium ions affected the lymphocyte counts. Method In a randomized controlled trial, we followed 19 RHA patients and 19 THA patients. Lymphocyte subsets and chromium and cobalt ion concentrations were measured at baseline, at 8 weeks, at 6 months, and at 1 and 2 years. Results The T–lymphocyte counts for both implant types declined over the 2–year period. This decline was statistically significant for CD3+CD8+ in the THA group, with a regression coefficient of –0.04 × 109cells/year (95% CI: –0.08 to –0.01). Regression analysis indicated a depressive effect of cobalt ions in particular on T–cells with 2–year whole–blood cobalt regression coefficients for CD3+ of –0.10 (95% CI: –0.16 to –0.04) × 109 cells/parts per billion (ppb), for CD3+CD4+ of –0.06 (–0.09 to –0.03) × 109 cells/ppb, and for CD3+CD8+ of –0.02 (–0.03 to –0.00) × 109 cells/ppb. Interpretation Circulating T–lymphocyte levels may decline after surgery, regardless of implant type. Metal ions—particularly cobalt—may have a general depressive effect on T– and B–lymphocyte levels. Registered with ClinicalTrials.gov under # NCT01113762 PMID:23597114

Use of Surveillance Data on HIV Diagnoses with HIV-Related Symptoms to Estimate the Number of People Living with Undiagnosed HIV in Need of Antiretroviral Therapy

PubMed Central

van Sighem, Ard; Sabin, Caroline A.; Phillips, Andrew N.

2015-01-01

Background It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART). Methods The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method. Results For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150–199 cells/mm3, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150–199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29–100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum. Conclusions The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count <200 cells/mm3 due to the low rate of developing HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART. PMID:25768925

Use of surveillance data on HIV diagnoses with HIV-related symptoms to estimate the number of people living with undiagnosed HIV in need of antiretroviral therapy.

PubMed

Lodwick, Rebecca K; Nakagawa, Fumiyo; van Sighem, Ard; Sabin, Caroline A; Phillips, Andrew N

2015-01-01

It is important to have methods available to estimate the number of people who have undiagnosed HIV and are in need of antiretroviral therapy (ART). The method uses the concept that a predictable level of occurrence of AIDS or other HIV-related clinical symptoms which lead to presentation for care, and hence diagnosis of HIV, arises in undiagnosed people with a given CD4 count. The method requires surveillance data on numbers of new HIV diagnoses with HIV-related symptoms, and the CD4 count at diagnosis. The CD4 count-specific rate at which HIV-related symptoms develop are estimated from cohort data. 95% confidence intervals can be constructed using a simple simulation method. For example, if there were 13 HIV diagnoses with HIV-related symptoms made in one year with CD4 count at diagnosis between 150-199 cells/mm3, then since the CD4 count-specific rate of HIV-related symptoms is estimated as 0.216 per person-year, the estimated number of person years lived in people with undiagnosed HIV with CD4 count 150-199 cells/mm3 is 13/0.216 = 60 (95% confidence interval: 29-100), which is considered an estimate of the number of people living with undiagnosed HIV in this CD4 count stratum. The method is straightforward to implement within a short period once a surveillance system of all new HIV diagnoses, collecting data on HIV-related symptoms at diagnosis, is in place and is most suitable for estimating the number of undiagnosed people with CD4 count <200 cells/mm3 due to the low rate of developing HIV-related symptoms at higher CD4 counts. A potential source of bias is under-diagnosis and under-reporting of diagnoses with HIV-related symptoms. Although this method has limitations as with all approaches, it is important for prompting increased efforts to identify undiagnosed people, particularly those with low CD4 count, and for informing levels of unmet need for ART.

Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

PubMed Central

Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carol L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W.; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G.; Lama, Javier R.; Rassool, Mohammed; Santos, Breno R.; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B.; Eshleman, Susan H.

2015-01-01

Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance–failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex–treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04–2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22–.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials Registration. NCT00084136. PMID:25681380

Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.

PubMed

Liu, X; Liu, H; Guo, Z; Luan, W

2006-01-01

To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.

Increase in CD4+ T-Cell Count at the Time of HIV Diagnosis and Antiretroviral Treatment Initiation Among Persons With HIV in New York City.

PubMed

Braunstein, Sarah L; Robertson, McKaylee M; Myers, Julie; Abraham, Bisrat; Nash, Denis

2016-12-01

 Trends in CD4 + T-cell count at human immunodeficiency virus (HIV) infection diagnosis and antiretroviral therapy (ART) initiation can be characterized using laboratory tests from surveillance.  We used CD4 + T-cell counts and viral loads from New York City for persons who received a diagnosis of HIV infection during 2006-2012.  From 2006 to 2012, the median CD4 + T-cell count increased from 325 to 379 cells/µL at diagnosis and from 178 to 360 cells/μL at ART initiation. CD4 + T-cell counts were consistently lower in women, blacks, Hispanics, persons who inject drugs, and heterosexuals.  Increases in CD4 + T-cell count at diagnosis and ART initiation suggest that the time from HIV infection to ART initiation has been reduced substantially in New York City. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Impact of Unplanned Care Interruption on CD4 Response Early After ART Initiation in a Nigerian Cohort.

PubMed

Ahonkhai, Aimalohi A; Adeola, Juliet; Banigbe, Bolanle; Onwuatuelo, Ifeyinwa; Adegoke, Abdulkabir B; Bassett, Ingrid V; Losina, Elena; Freedberg, Kenneth A; Okonkwo, Prosper; Regan, Susan

The authors conducted a retrospective cohort study of unplanned care interruption (UCI) among adults initiating antiretroviral therapy (ART) from 2009 to 2011 in a Nigerian clinic. The authors used repeated measures regression to model the impact of UCI on CD4 count upon return to care and rate of CD4 change on ART. Among 2496 patients, 83% had 0, 15% had 1, and 2% had ≥2 UCIs. Mean baseline CD4 for those with 0, 1, or ≥2 UCIs was 228/cells/mm 3 , 355/cells/mm 3 , and 392/cells/mm 3 ( P < .0001), respectively. The UCI was associated with a 62 CD4 cells/mm 3 decrease (95% confidence interval [CI]: -78 to -45) at next measurement. In months 1 to 6 on ART, patients with 0 UCI gained 10 cells/µL/mo (95% CI: 7-4). Those with 1 and ≥2 UCIs lost 2 and 5 cells/µL/mo (95% CI: -18 to 13 and -26 to 16). Patients with UCI did not recover from early CD4 losses associated with UCI. Preventing UCI is critical to maximize benefits of ART.

Indian Adolescent Living with HIV-AIDS: Current Clinical Scenario.

PubMed

Joshi, Kavita S; Bhaware, Bhushan D; Pazare, Amar R

2017-07-01

Statistics suggest that, HIV has now largely become the disease of young patients. Hence, the adolescent HIV/AIDS needs to be handled and managed separately from adult HIV. Relatively fewer Indian data exist to characterize the associations in adolescents and young adults infected with HIV disease. The present study explores the current challenges in the management of HIV infected adolescents. The study was aimed at evaluating, relationship between CD4 count and duration of antiretroviral therapy (ART), effects of ART on body mass index and the adverse effects of antiretroviral drugs in adolescent HIV positive patients. This was a cross-sectional study involving 60 HIV positive adolescent patients attending tertiary care Institute KEM Hospital, Parel over duration of one year conducted at Mumbai. Patients on ART between age group 12 to 19 years. ART naïve patients were excluded from the study. 60 adolescent HIV positive patients attended our OPD including 37 males (61.67%) and 23 females (38.33%).The most common mode of transmission was vertical (80%). Education level was: school dropouts - 15%, primary education - 30%, Completed SSC - 31.7%, higher secondary - 23%. Among ADRs were 12 (63.15%) cases of anaemia due to Zidovudine, 4 (21.05%) hepatitis due to Nevirapine, 2 (10.52%) Tenofovir induced AKI and 1 (5.26%) Nevirapine rash. Wilcoxon matched pairs test showed a highly significant increase in the BMI (p <0.0001) post therapy. The mean CD4 of the patients at baseline and current presentation was 295.57 ± 109.81 and 630.93 ± 188.70 cells/mm3 respectively. The CD4 count was seen to be increasing with the increase in the duration of HAART treatment. High efficacy of HAART and availability of free ART under government programme has increased the duration of survival of the adolescent population with HIV. Treatment with HAART showed a favourable response with a statistical significant increase in CD4 count. Longer the duration of HAART, higher was the gain in CD4 count. Indian adolescent receiving long term ART, Lipodystrophy is not a troubling issue. Indian adolescent seems to be more tolerance of ART than the other parts of world.

Clinical outcomes of first-line antiretroviral therapy in Latin America: analysis from the LATINA retrospective cohort study.

PubMed

Angriman, Federico; Belloso, Waldo H; Sierra-Madero, Juan; Sánchez, Jorge; Moreira, Ronaldo Ismerio; Kovalevski, Leandro O; Orellana, Liliana C; Cardoso, Sandra Wagner; Crabtree-Ramirez, Brenda; La Rosa, Alberto; Losso, Marcelo H

2016-02-01

Nearly 2 million people are infected with human immunodeficiency virus (HIV) in Latin America. However, information regarding population-scale outcomes from a regional perspective is scarce. We aimed to describe the baseline characteristics and therapeutic outcomes of newly-treated individuals with HIV infection in Latin America. A Retrospective cohort study was undertaken. The primary explanatory variable was combination antiretroviral therapy based on either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI). The main outcome was defined as the composite of all-cause mortality and the occurrence of an AIDS-defining clinical event or a serious non-AIDS-defining event during the first year of therapy. The secondary outcomes included the time to a change in treatment strategy. All analyses were performed according to the intention to treat principle. A total of 937 treatment-naive patients from four participating countries were included (228 patients with PI therapy and 709 with NNRTI-based treatment). At the time of treatment initiation, the patients had a mean age of 37 (SD: 10) years and a median CD4 + T-cell count of 133 cells/mm(3) (interquartile range: 47.5-216.0). Patients receiving PI-based regimens had a significantly lower CD4 + count, a higher AIDS prevalence at baseline and a shorter time from HIV diagnosis until the initiation of treatment. There was no difference in the hazard ratio for the primary outcome between groups. The only covariates associated with the latter were CD4 + cell count at baseline, study site and age. The estimated hazard ratio for the time to a change in treatment (NNRTI vs PI) was 0.61 (95% CI 0.47-0.80, p < 0.01). This study concluded that patients living with HIV in Latin America present with similar clinical outcomes regardless of the choice of initial therapy. Patients treated with PIs are more likely to require a treatment change during the first year of follow up. © The Author(s) 2015.

Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

PubMed

Van Rie, Annelies; Patel, Monita R; Nana, Mbonze; Vanden Driessche, Koen; Tabala, Martine; Yotebieng, Marcel; Behets, Frieda

2014-03-01

A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100-350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

Acceptability of Early Antiretroviral Therapy Among South African Women.

PubMed

Garrett, Nigel; Norman, Emily; Leask, Kerry; Naicker, Nivashnee; Asari, Villeshni; Majola, Nelisile; Karim, Quarraisha Abdool; Karim, Salim S Abdool

2018-03-01

WHO guidelines recommend immediate initiation of antiretroviral therapy (ART) for all individuals at HIV diagnosis regardless of CD4 count, but concerns remain about potential low uptake or poor adherence among healthy patients with high CD4 counts, especially in resource-limited settings. This study assessed the acceptability of earlier treatment among HIV-positive South African women, median age at enrollment 25 (IQR 22-30), in a 10 year prospective cohort study by (i) describing temporal CD4 count trends at initiation in relation to WHO guidance, (ii) virological suppression rates post-ART initiation at different CD4 count thresholds, and (iii) administration of a standardized questionnaire. 158/232 (68.1%) participants initiated ART between 2006 and 2015. Mean CD4 count at initiation was 217 cells/µl (range 135-372) before 2010, and increased to 531 cells/µl (range 272-1095) by 2015 (p < 0.001). Median viral load at ART initiation decreased over this period from 5.2 (IQR 4.6-5.6) to 4.1 (IQR 3.4-4.6) log copies/ml (p = 0.004). Virological suppression rates at 3, 6, 12 and 18 months were consistently above 85% with no statistically significant differences for participants starting ART at different CD4 count thresholds. A questionnaire assessing uptake of early ART amongst ART-naïve women, median age 28 (IQR 24-33), revealed that 40/51 (78.4%) were willing to start ART at CD4 ≥500. Of those unwilling, 6/11 (54.5%) started ART within 6 months of questionnaire administration. Temporal increases in CD4 counts, comparable virological suppression rates, and positive patient perceptions confirm high acceptability of earlier ART initiation for the majority of patients.

Fluorescent intensity-based differential counting of FITC-doped silica nanoparticles: applications of CD4+ T-cell detection in microchip-type flowcytometers

NASA Astrophysics Data System (ADS)

Yun, Hoyoung; Bang, Hyunwoo; Lee, Won Gu; Lim, Hyunchang; Park, Junha; Lee, Joonmo; Riaz, Asif; Cho, Keunchang; Chung, Chanil; Han, Dong-Chul; Chang, Jun Keun

2007-12-01

Although CD4+ T-cells are an important target of HIV detection, there have been still major problems in making a diagnosis and monitoring in the third world and the region with few medical facilities. Then, it is necessary to use portable diagnosis devices at low cost when you put an enumeration of CD4+ T-cells. In general, the counting of CD4 below 200cells/uL makes it necessary to initiate antiretroviral treatment in adults (over 13 years old). However, lymphocyte subsets (including CD4 counts) of infants and young children are higher than those of adults. This fact shows the percentage of CD4+ T-cells of blood subsets, i.e., CD4/CD45%, CD4/CD8% or CD4/CD3% means a more reliable indicator of HIV infection than absolute counts in children. To know the percentage of CD4+ T-cell by using two fluorescent dyes of different emission wavelength, at least, one laser and two PMT detectors are in general needed. Then, it is so hard to develop a portable device like a 'toaster size' because this makes such a device more complex including many peripheral modules. In this study, we developed a novel technique to control the intensity of fluorescent dye-doped silica nanoparticles. I synthesized FITC-doped silica nanoparticles conjugated CD4 antibody 10 times brighter than FITC-conjugated CD45 antibody. With the difference of intensity of two fluorescent dyes, we measured two parameters by using only a single detector and laser. Most experiments were achieved with uFACS (microfabricated fluorescence-activated cell sorter) on an inverted microscope (IX71, Olympus). In conclusion, this method enables us to discriminate the difference between CD4 and CD45 in an intensity domain simultaneously. Furthermore, this technique would make it possible develop much cheaper and smaller devices which can count the number of CD4 T-cells.

Treatment eligibility and retention in clinical HIV care: A regression discontinuity study in South Africa

PubMed Central

Bor, Jacob; Tanser, Frank; Bärnighausen, Till

2017-01-01

Background Loss to follow-up is high among HIV patients not yet receiving antiretroviral therapy (ART). Clinical trials have demonstrated the clinical efficacy of early ART; however, these trials may miss an important real-world consequence of providing ART at diagnosis: its impact on retention in care. Methods and findings We examined the effect of immediate (versus deferred) ART on retention in care using a regression discontinuity design. The analysis included all patients (N = 11,306) entering clinical HIV care with a first CD4 count between 12 August 2011 and 31 December 2012 in a public-sector HIV care and treatment program in rural South Africa. Patients were assigned to immediate versus deferred ART eligibility, as determined by a CD4 count < 350 cells/μl, per South African national guidelines. Patients referred to pre-ART care were instructed to return every 6 months for CD4 monitoring. Patients initiated on ART were instructed to return at 6 and 12 months post-initiation and annually thereafter for CD4 and viral load monitoring. We assessed retention in HIV care at 12 months, as measured by the presence of a clinic visit, lab test, or ART initiation 6 to 18 months after initial CD4 test. Differences in retention between patients presenting with CD4 counts just above versus just below the 350-cells/μl threshold were estimated using local linear regression models with a data-driven bandwidth and with the algorithm for selecting the bandwidth chosen ex ante. Among patients with CD4 counts close to the 350-cells/μl threshold, having an ART-eligible CD4 count (<350 cells/μl) was associated with higher 12-month retention than not having an ART-eligible CD4 count (50% versus 32%), an intention-to-treat risk difference of 18 percentage points (95% CI 11 to 23; p < 0.001). The decision to start ART was determined by CD4 count for one in four patients (25%) presenting close to the eligibility threshold (95% CI 20% to 31%; p < 0.001). In this subpopulation, having an ART-eligible CD4 count was associated with higher 12-month retention than not having an ART-eligible CD4 count (91% versus 21%), a complier causal risk difference of 70 percentage points (95% CI 42 to 98; p < 0.001). The major limitations of the study are the potential for limited generalizability, the potential for outcome misclassification, and the absence of data on longer-term health outcomes. Conclusions Patients who were eligible for immediate ART had dramatically higher retention in HIV care than patients who just missed the CD4-count eligibility cutoff. The clinical and population health benefits of offering immediate ART regardless of CD4 count may be larger than suggested by clinical trials. PMID:29182641

Plasma Soluble CD163 Level Independently Predicts All-Cause Mortality in HIV-1-Infected Individuals.

PubMed

Knudsen, Troels Bygum; Ertner, Gideon; Petersen, Janne; Møller, Holger Jon; Moestrup, Søren K; Eugen-Olsen, Jesper; Kronborg, Gitte; Benfield, Thomas

2016-10-15

CD163, a monocyte- and macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association between plasma sCD163 levels and progression to AIDS and all-cause mortality among individuals infected with human immunodeficiency virus type 1 (HIV). Plasma sCD163 levels were measured in 933 HIV-infected individuals. Hazard ratios (HRs) with 95% confidence intervals (CIs) associated with mortality were computed by Cox proportional hazards regression. At baseline, 86% were receiving antiretroviral treatment, 73% had plasma a HIV RNA level of <50 copies/mL, and the median CD4(+) T-cell count was 503 cells/µL. During 10.5 years of follow-up, 167 (17.9%) died. Plasma sCD163 levels were higher in nonsurvivors than in survivors (4.92 mg/L [interquartile range {IQR}, 3.29-8.65 mg/L] vs 3.16 mg/L [IQR, 2.16-4.64 mg/L]; P = .0001). The cumulative incidence of death increased with increasing plasma sCD163 levels, corresponding to a 6% or 35% increased risk of death for each milligram per liter or quartile increase, respectively, in baseline plasma sCD163 level (adjusted HR, 1.06 [95% CI, 1.03-1.09] and 1.35 [95% CI, 1.13-1.63], respectively). Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV-infected individuals, suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Food insecurity, CD4 counts, and incomplete viral suppression among HIV+ patients from Texas Children's Hospital: A pilot study

USDA-ARS?s Scientific Manuscript database

Our goal was to determine the relationship between food insecurity and CD4 counts and viral suppression among pediatric HIV-positive patients. Food insecurity was assessed by validated survey. CD4 counts and viral load were abstracted from patients’ charts. We used linear regression for the dependen...

Antiretroviral Service to HIV patients of low CD4 count in Seti Zonal Hospital.

PubMed

Paudel, B N; Chaudhary, S R; Sharma, S; Dhungana, G P; Paudel, P

2009-01-01

Due to unavailability of vaccine against HIV/AIDS, there are no ways other than relying on ART. We select group of late stage HIV/AIDS with CD4<50 so that opportunistic infections and outcome of patients in this late stage of severe immunosuppression after initiation of ART can be known A cross sectional study was carried out in 53 HIV patients with CD4 count <50 cells/cu mm blood undergoing ART in Seti Zonal Hospital Dhangadi between December 2006 and May 2008 with objectives to explore the treatment outcome in this late stage of immunosuppression. Only those patients with CD4 count <50 were consecutively selected and recommended for various laboratory test on the basis of which ART regimen were prescribed. Among 53 patients, 42 (79.2%) were males and 11 (20.8%) were females, with predominant age group of 30-40 years (49.1%). Fever (71.7%), diarrhea (56.6%), pneumonia (52.8%), weight loss (52.8%) and oral thrush (33.9%) were found to be the major clinical presentation/Opportunistic infections. 19 (35.8%) patients showed normal activity throughout the treatment period with increase in CD4 count, 10 (19%) were recovered and transferred out. Only 1 (1.8%) showed decrease in CD4 count even after taking ART. Significant relationship was established between the intake of ART and increase in CD4 level (pair t = 7.88, p<0.05). ART service was found to be efficient enough to increase the CD4 count significantly after 6 months of therapy but the prevalence of OIs/clinical manifestations were sufficiently higher in this group of patients with low CD4 count.

Validation of World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy and clinical predictors of low CD4 cell count in Uganda.

PubMed

Baveewo, Steven; Ssali, Francis; Karamagi, Charles; Kalyango, Joan N; Hahn, Judith A; Ekoru, Kenneth; Mugyenyi, Peter; Katabira, Elly

2011-05-12

The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3). To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.

Association Between HIV-1 RNA Level and CD4 Cell Count Among Untreated HIV-Infected Individuals

PubMed Central

Lima, Viviane D.; Fink, Valeria; Yip, Benita; Hogg, Robert S.; Harrigan, P. Richard

2009-01-01

Objectives. We examined the significance of plasma HIV-1 RNA levels (or viral load alone) in predicting CD4 cell decline in untreated HIV-infected individuals. Methods. Data were obtained from the British Columbia Centre for Excellence in HIV/AIDS. Participants included all residents who ever had a viral load determination in the province and who had never taken antiretroviral drugs (N = 890). We analyzed a total of 2074 viral load measurements and 2332 CD4 cell counts. Linear mixed-effects models were used to predict CD4 cell decline over time. Results. Longitudinal viral load was strongly associated with CD4 cell decline over time; an average of 1 log10 increase in viral load was associated with a 55-cell/mm3 decrease in CD4 cell count. Conclusions. Our results support the combined use of CD4 cell count and viral load as prognostic markers in HIV-infected individuals before the introduction of antiretroviral therapy. PMID:19218172

Delayed-type hypersensitivity (DTH) test anergy does not impact CD4 reconstitution or normalization of DTH responses during antiretroviral therapy.

PubMed

Minidis, Natascha M; Mesner, Octavio; Agan, Brian K; Okulicz, Jason F

2014-01-01

Delayed-type hypersensitivity (DTH) testing is an in vivo assessment of cell-mediated immunity. Although highly active antiretroviral therapy (HAART) improves immunologic parameters, the relationship between DTH responsiveness and CD4 gains on HAART is not completely understood. We investigated CD4 reconstitution and the change in DTH responses from treatment baseline through 24 months of viral load (VL)-suppressive HAART in the U.S. Military HIV Natural History Study. Treatment-naïve subjects with VL <400 copies/mL after ≥24 months on HAART were included (n=302). DTH testing consisted of ≥3 recall antigens, and responses were classified by the number of positive skin tests: anergic (0-1) or non-anergic (≥2). Pre-HAART DTH results were compared for the outcome of CD4 reconstitution at 24 months of HAART. Improvement in DTH responses was also analyzed for those anergic before HAART initiation. Non-anergic responses were observed in 216 (72%) participants, while 86 (28%) individuals were anergic prior to HAART initiation. Demographically there were similar distributions of age at HIV diagnosis and HAART initiation, as well as gender and race or ethnicity. There were no significant differences between non-anergic and anergic participants in pre-HAART CD4 count (409 cells/μL, interquartile range (IQR) 315-517 vs. 373 cells/μL, IQR 228-487; p=0.104) and VL (4.3 log10 copies/mL, IQR 3.4-4.9 vs. 4.4 log10 copies/mL, IQR 3.6-5.0; p=0.292). Median CD4 gains 24 months after HAART initiation were similar between the non-anergic (220 cells/μL, IQR 115-358) and anergic groups (246 cells/μL, IQR 136-358; p=0.498). For individuals anergic before HAART initiation, DTH normalization occurred at 24 months post-HAART in the majority of participants (51 of 86, 59%). Normalization of DTH responses was not associated with CD4 count at HAART initiation (OR 0.73, 95% CI 0.47, 1.09 per 100 cells; p=0.129) nor with AIDS diagnoses prior to HAART (OR 0.34, 95% CI 0.04, 2.51; p=0.283). DTH responsiveness has been shown to predict HIV disease progression independent of CD4 count in untreated individuals. In the setting of HAART, pre-HAART anergy does not appear to impact CD4 gains or the ability to normalize DTH responses after 24 months of VL-suppressive HAART.

Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286.

PubMed

Tenorio, Allan R; Chan, Ellen S; Bosch, Ronald J; Macatangay, Bernard J C; Read, Sarah W; Yesmin, Suria; Taiwo, Babafemi; Margolis, David M; Jacobson, Jeffrey M; Landay, Alan L; Wilson, Cara C

2015-03-01

Rifaximin, a nonabsorbable antibiotic that decreases lipopolysaccharide (LPS) in cirrhotics, may decrease the elevated levels of microbial translocation, T-cell activation and inflammation in human immunodeficiency virus (HIV)-positive immune nonresponders to antiretroviral therapy (ART). HIV-positive adults receiving ART for ≥96 weeks with undetectable viremia for ≥48 weeks and CD4(+) T-cell counts <350 cells/mm(3) were randomized 2:1 to rifaximin versus no study treatment for 4 weeks. T-cell activation, LPS, and soluble CD14 were measured at baseline and at weeks 2, 4, and 8. Wilcoxon rank sum tests compared changes between arms. Compared with no study treatment (n = 22), rifaximin (n = 43) use was associated with a significant difference between study arms in the change from baseline to week 4 for CD8(+)T-cell activation (median change, 0.0% with rifaximin vs +0.6% with no treatment; P = .03). This difference was driven by an increase in the no-study-treatment arm because there was no significant change within the rifaximin arm. Similarly, although there were significant differences between study arms in change from baseline to week 2 for LPS and soluble CD14, there were no significant changes within the rifaximin arm. In immune nonresponders to ART, rifaximin minimally affected microbial translocation and CD8(+)T-cell activation. Trial registration number. NCT01466595. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Systematic review of statistically-derived models of immunological response in HIV-infected adults on antiretroviral therapy in Sub-Saharan Africa.

PubMed

Sempa, Joseph B; Ujeneza, Eva L; Nieuwoudt, Martin

2017-01-01

In Sub-Saharan African (SSA) resource limited settings, Cluster of Differentiation 4 (CD4) counts continue to be used for clinical decision making in antiretroviral therapy (ART). Here, HIV-infected people often remain with CD4 counts <350 cells/μL even after 5 years of viral load suppression. Ongoing immunological monitoring is necessary. Due to varying statistical modeling methods comparing immune response to ART across different cohorts is difficult. We systematically review such models and detail the similarities, differences and problems. 'Preferred Reporting Items for Systematic Review and Meta-Analyses' guidelines were used. Only studies of immune-response after ART initiation from SSA in adults were included. Data was extracted from each study and tabulated. Outcomes were categorized into 3 groups: 'slope', 'survival', and 'asymptote' models. Wordclouds were drawn wherein the frequency of variables occurring in the reviewed models is indicated by their size and color. 69 covariates were identified in the final models of 35 studies. Effect sizes of covariates were not directly quantitatively comparable in view of the combination of differing variables and scale transformation methods across models. Wordclouds enabled the identification of qualitative and semi-quantitative covariate sets for each outcome category. Comparison across categories identified sex, baseline age, baseline log viral load, baseline CD4, ART initiation regimen and ART duration as a minimal consensus set. Most models were different with respect to covariates included, variable transformations and scales, model assumptions, modelling strategies and reporting methods, even for the same outcomes. To enable comparison across cohorts, statistical models would benefit from the application of more uniform modelling techniques. Historic efforts have produced results that are anecdotal to individual cohorts only. This study was able to define 'prior' knowledge in the Bayesian sense. Such information has value for prospective modelling efforts.

Higher plasma CD4 lymphocyte count correlates with better cognitive function in human immunodeficiency virus-acquired immunodeficiency syndrome (HIV-AIDS) patients

NASA Astrophysics Data System (ADS)

Fitri, F. I.; Rambe, A. S.; Fitri, A.

2018-03-01

Neurocognitive disorders in HIV-AIDS are still prevalent despite the use of antiretroviral therapy and seem to be under-recognized. Plasma lymphocyte CD4 count is a marker for general immunology status, but its association with cognitive function remains unclear. The aim of this study was to determine the correlation between plasma CD4 lymphocyte and cognitive function in HIV-AIDS patients.This was a cross-sectional study involving 48 HIV-AIDS patients. All subjects underwent physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts.This study included 48 subjects consisted of 29 males (60.4%) and 19 females (39.6%). The mean age was 39.17±11.21 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r=0.347, p=0.016).Higher plasma CD4 lymphocyte count is correlated with better cognitive function in HIV-AIDS patients.

Antiretroviral therapy suppressed participants with low CD4+ T-cell counts segregate according to opposite immunological phenotypes

PubMed Central

Pérez-Santiago, Josué; Ouchi, Dan; Urrea, Victor; Carrillo, Jorge; Cabrera, Cecilia; Villà-Freixa, Jordi; Puig, Jordi; Paredes, Roger; Negredo, Eugènia; Clotet, Bonaventura; Massanella, Marta; Blanco, Julià

2016-01-01

Background: The failure to increase CD4+ T-cell counts in some antiretroviral therapy suppressed participants (immunodiscordance) has been related to perturbed CD4+ T-cell homeostasis and impacts clinical evolution. Methods: We evaluated different definitions of immunodiscordance based on CD4+ T-cell counts (cutoff) or CD4+ T-cell increases from nadir value (ΔCD4) using supervised random forest classification of 74 immunological and clinical variables from 196 antiretroviral therapy suppressed individuals. Unsupervised clustering was performed using relevant variables identified in the supervised approach from 191 individuals. Results: Cutoff definition of CD4+ cell count 400 cells/μl performed better than any other definition in segregating immunoconcordant and immunodiscordant individuals (85% accuracy), using markers of activation, nadir and death of CD4+ T cells. Unsupervised clustering of relevant variables using this definition revealed large heterogeneity between immunodiscordant individuals and segregated participants into three distinct subgroups with distinct production, programmed cell-death protein-1 (PD-1) expression, activation and death of T cells. Surprisingly, a nonnegligible number of immunodiscordant participants (22%) showed high frequency of recent thymic emigrants and low CD4+ T-cell activation and death, very similar to immunoconcordant participants. Notably, human leukocyte antigen - antigen D related (HLA-DR) PD-1 and CD45RA expression in CD4+ T cells allowed reproducing subgroup segregation (81.4% accuracy). Despite sharp immunological differences, similar and persistently low CD4+ values were maintained in these participants over time. Conclusion: A cutoff value of CD4+ T-cell count 400 cells/μl classified better immunodiscordant and immunoconcordant individuals than any ΔCD4 classification. Immunodiscordance may present several, even opposite, immunological patterns that are identified by a simple immunological follow-up. Subgroup classification may help clinicians to delineate diverse approaches that may be needed to boost CD4+ T-cell recovery. PMID:27427875

Nevirapine/zidovudine/lamivudine has superior immunological and virological responses not reflected in clinical outcomes in a 48-week randomized comparison with abacavir/zidovudine/lamivudine in HIV-infected Ugandan adults with low CD4 cell counts.

PubMed

Munderi, P; Walker, A S; Kityo, C; Babiker, A G; Ssali, F; Reid, A; Darbyshire, J H; Grosskurth, H; Mugyenyi, P; Gibb, D M; Gilks, C F

2010-05-01

Triple nucleoside reverse transcriptase inhibitor regimens have advantages as first-line antiretroviral therapy (ART), avoiding hepatotoxicity and interactions with anti-tuberculosis therapy, and sparing two drug classes for second-line ART. Concerns exist about virological potency; efficacy has not been assessed in Africa. A safety trial comparing nevirapine with abacavir was conducted in two Ugandan Development of Antiretroviral Therapy in Africa (DART) centres: 600 symptomatic antiretroviral-naïve HIV-infected adults with CD4 counts <200 cells/microL were randomized to zidovudine/lamivudine plus abacavir or nevirapine (placebo-controlled to 24-week primary toxicity endpoint, and then open-label). Documented World Health Organization (WHO) stage 4 events were independently reviewed and plasma HIV-1 RNA assayed retrospectively. Exploratory efficacy analyses are intention-to-treat. The median pre-ART CD4 count was 99 cells/microL, and the median pre-ART viral load was 284 600 HIV-1 RNA copies/mL. A total of 563 participants (94%) completed 48 weeks of follow-up, 25 (4%) died and 12 (2%) were lost to follow-up. The randomized drug was substituted in 21 participants (7%) receiving abacavir vs. 34 (11%) receiving nevirapine (P=0.09). At 48 weeks, 62% of participants receiving abacavir vs. 77% of those receiving nevirapine had viral loads <50 copies/mL (P<0.001), and mean CD4 count increases from baseline were +147 vs. +173 cells/microL, respectively (P=0.006). Nine participants (3%) receiving abacavir vs. 16 (5%) receiving nevirapine died [hazard ratio (HR) 0.55; 95% confidence interval (CI) 0.24-1.25; P=0.15]; 20 receiving abacavir vs. 32 receiving nevirapine developed new or recurrent WHO 4 events or died (HR=0.60; 95% CI 0.34-1.05; P=0.07) and 48 receiving abacavir vs. 68 receiving nevirapine developed new or recurrent WHO 3 or 4 events or died (HR=0.67; 95% CI 0.46-0.96; P=0.03). Seventy-one participants (24%) receiving abacavir experienced 91 grade 4 adverse events compared with 130 events in 109 participants (36%) on nevirapine (P<0.001). The clear virological/immunological superiority of nevirapine over abacavir was not reflected in clinical outcomes over 48 weeks. The inability of CD4 cell count/viral load to predict initial clinical treatment efficacy is unexplained and requires further evaluation.

Risk factors associated with low CD4+ lymphocyte count among HIV-positive pregnant women in Nigeria.

PubMed

Abimiku, Alash'le; Villalba-Diebold, Pacha; Dadik, Jelpe; Okolo, Felicia; Mang, Edwina; Charurat, Man

2009-09-01

To determine the risk factors for CD4+ lymphocyte counts of 200 cells/mm(3) or lower in HIV-positive pregnant women in Nigeria. A cross-sectional data analysis from a prospective cohort of 515 HIV-positive women attending a prenatal clinic. Risk of a low CD4+ count was estimated using logistic regression analysis. CD4+ lymphocyte counts of 200 cells/mm(3) or lower (280+/-182 cells/mm(3)) were recorded in 187 (36.3%) out of 515 HIV-positive pregnant women included in the study. Low CD4+ count was associated with older age (adjusted odds ratio [aOR] 10.71; 95% confidence interval [CI], 1.20-95.53), lack of condom use (aOR, 5.16; 95% CI, 1.12-23.8), history of genital ulcers (aOR, 1.78; 95% CI, 1.12-2.82), and history of vaginal discharge (aOR; 1.62; 1.06-2.48). Over 35% of the HIV-positive pregnant women had low CD4+ counts, indicating the need for treatment. The findings underscore the need to integrate prevention of mother-to-child transmission with HIV treatment and care, particularly services for sexually transmitted infections.

[Association of CD(+)4 T lymphocyte count and gingival crevicular fluid prostaglandin E2 with periodontal parameters in HIV-positive periodontitis patients].

PubMed

Jia, Hongcheng; Wang, Xuan; Hua, Wenhao; Li, Xiaoguang; Hou, Wen; Fu, Qian

2014-02-01

To investigate the correlation of CD(+)4 T lymphocyte count and prostaglandin E2 (PGE2) in gingival crevicular fluid (GCF) with periodontal status in HIV-positive patients with periodontitis. Twenty subjects were selected according to inclusion criteria. The plasmatic CD(+)4 T lymphocytes were counted. All the individuals were divided into three groups, group A (CD(+)4 T lymphocyte count < 200 cell/mm(3)), group B (200 cell/mm(3) ≤ CD(+)4 T lymphocyte count ≤ 500 cell/mm(3)) and group C (CD(+)4 T lymphocyte count > 500 cell/mm(3)). Periodontal indexes, including plaque index(PLI), bleeding index(BI), attachment level(AL) and probing depth(PD) were recorded.GCF samples were taken from 120 index teeth by means of sterile paper strips.GCF PGE2 levels were determined by radioimmunoassays. Mann-Whitney was used to compare the periodontal indexes and PGE2 levels among the three groups. Partial correlations and Spearman correlations were applied to analyze the correlation of CD(+)4 T lymphocytes count and PGE2 in gingival crevicular fluid with periodontal status. BI value, PGE2 concentration and total PGE2 were 3.00(2.00), 90.75(30.60) µg/L, 447.58 (243.08) pg in group B, which were higher than those in group A[2.00(1.25), 79.75(30.50) µg/L and 339.52 (200.97) pg respectively] and group C[2.00(1.00), 73.38 (14.83) µg/L and 299.18 (108.33) pg respectively] (P < 0.0167). But the differences of PD and AL among the three groups were not significantly different(P > 0.0167). The correlations were observed between CD(+)4 T lymphocyte count and BI for the subpopulations with CD(+)4 T lymphocyte count <200 cells/mm(3) (r = 0.657, P < 0.05) and between 200-500 cells/mm(3) (r = -0.369, P < 0.05). PGE2 concentration was negatively correlated with BI, PD and AL (P < 0.05), and total PGE2 was positively correlated with PD and AL(P < 0.05). There was an association between the periodontal status and CD(+)4 T lymphocyte count in HIV(+) patients.GCF PGE2 level was related to periodontal parameters including BI, PD and AL.

Responses to highly active antiretroviral therapy and clinical events in patients with a low CD4 cell count: late presenters vs. late starters.

PubMed

Waters, L; Fisher, M; Anderson, J; Wood, C; Delpech, V; Hill, T; Walsh, J; Orkin, C; Bansi, L; Gompels, M; Phillips, A; Johnson, M; Gilson, R; Easterbrook, P; Leen, C; Porter, K; Gazzard, B; Sabin, C

2011-05-01

We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors. A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) Study of individuals starting HAART in 1998-2007 was carried out, comparing late presenters (presenting/starting HAART at a CD4 count <200 cells/μL) with late starters (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count<200 cells/μL), using 'ideal starters' (presenting at a CD4 count>350 cells/μL; starting HAART at a CD4 count of 200-350 cells/μL) as a comparator. Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for>3 months. A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA>500 HIV-1 RNA copies/mL were included in the analysis: 2741 late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19-3.51; P=0.01]; by year 2, event rates were similar in all groups. Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal starters. Differences between late presenters and late starters suggest that factors other than CD4 cell count alone may be driving adverse treatment outcomes in late-presenting individuals.

Sex Differences in Antiretroviral Therapy Initiation in Pediatric HIV Infection

PubMed Central

Swordy, Alice; Mori, Luisa; Laker, Leana; Muenchhoff, Maximilian; Matthews, Philippa C.; Tudor-Williams, Gareth; Lavandier, Nora; van Zyl, Anriette; Hurst, Jacob; Walker, Bruce D.; Ndung’u, Thumbi; Prendergast, Andrew; Goulder, Philip; Jooste, Pieter

2015-01-01

The incidence and severity of infections in childhood is typically greater in males. The basis for these observed sex differences is not well understood, and potentially may facilitate novel approaches to reducing disease from a range of conditions. We here investigated sex differences in HIV-infected children in relation to antiretroviral therapy (ART) initiation and post-treatment outcome. In a South African cohort of 2,101 HIV-infected children, we observed that absolute CD4+ count and CD4% were significantly higher in ART-naïve female, compared to age-matched male, HIV-infected children. Absolute CD4 count and CD4% were also significantly higher in HIV-uninfected female versus male neonates. We next showed that significantly more male than female children were initiated on ART (47% female); and children not meeting criteria to start ART by >5yrs were more frequently female (59%; p<0.001). Among ART-treated children, immune reconstitution of CD4 T-cells was more rapid and more complete in female children, even after adjustment for pre-ART absolute CD4 count or CD4% (p=0.011, p=0.030, respectively). However, while ART was initiated as a result of meeting CD4 criteria less often in females (45%), ART initiation as a result of clinical disease in children whose CD4 counts were above treatment thresholds occurred more often in females (57%, p<0.001). The main sex difference in morbidity observed in children initiating ART above CD4 thresholds, above that of TB disease, was as a result of wasting and stunting observed in females with above-threshold CD4 counts (p=0.002). These findings suggest the possibility that optimal treatment of HIV-infected children might incorporate differential CD4 treatment thresholds for ART initiation according to sex. PMID:26151555

[Relationship between CD4(+) T lymphocyte cell count and the prognosis (including the healing of the incision wound) of HIV/AIDS patients who had undergone surgical operation].

PubMed

Yang, Di; Zhao, Hongxin; Gao, Guiju; Wei, Kai; Zhang, Li; Han, Ning; Xiao, Jiang; Li, Xin; Wang, Fang; Liang, Hongyuan; Zhang, Wei; Wu, Liang

2014-12-01

To explore the relationship between CD4(+) T lymphocyte cell count and prognosis as well as healing of the surgical incision in HIV/AIDS patients who had received operation. Data were collected and analysed retrospectively from 234 HIV/AIDS patients hospitalized at the Beijing Ditan hospital who underwent operation between January 2008 and December 2012. Following factors were taken into consideration that including:age, gender, time and where that anti-HIV(+) was diagnosed, CD4(+)T lymphocyte cell count at the time of operation, part of the body that being operated, typology of incision, different levels of healing on the surgical incision, infection at the incision site, post-operative complications and the prognosis, etc. Wilcoxon rank sum test, χ(2) test, Kruskal-Wallis H test and Spearman rank correlation were used for statistical analysis to compare the different levels on healing of the incision in relation to the different CD4(+)T lymphocyte cell counts. Rates of level A healing under different CD4(+)T cell counts were also compared. 1) Among the 234 patients including 125 males and 109 females, the average age was 36.17±11.56 years old. Time after discovery of anti-HIV(+)was between 0 and 204 months. The medium CD4(+)T cell count was 388.5 cell/µl; 23.93% of the patients having CD4(+)T lymphocyte cell counts as <200 cell/µl. 2) 7.26% of the operations were emergent. There were 23 different organs affected at the time of operation, due to 48 different kinds of illness. 21.37% of the operations belonged to class I incision, 49.57% was class II incision and 29.06% was class III incision. 86.32% of the incisions resulted in level A healing, 12.51% resulted in level B and 1.71% in level C. 4.27% of the patients developed post-operative complications. Differences between level A healing and level B or C healing in terms of CD4(+)T lymphocyte cell count were not significant (P > 0.05). There was no statistically significant difference on the CD4(+) T lymphocyte count in patients with or without postoperative complications. Difference of the HIV infection time was also not statistically significant between the two groups of patients. Rate of level A healing for the different CD4(+)T lymphocyte cell count was not significant (P > 0.05). Healing of the incision did not show significant correlation with CD4(+) T lymphocyte cell count, duration of antiretroviral therapy or the time that HIV infection was discovered (P > 0.05). As long as both the in/exclusion criteria were strictly followed, prognosis for operation on HIV/AIDS seemed to be generally good. Low CD4(+)T lymphocyte cell count should not be taken as a exclusion criteria for operation on HIV/AIDS patients.

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults

PubMed Central

Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H.; García, Felipe.; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L.; Mounzer, Karam; Swindells, Susan; Baxter, John D.; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

2016-01-01

Abstract The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults. This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4+ T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks. At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): −0.088; 0.235]), or F4/AS01B_3 and control group (−0.096 log10 copies/mL [97.5% CI: −0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4+ T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4+ T-cells, but had no significant impact on F4-specific CD8+ T-cell and anti-F4 antibody levels. F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4+ T-cell responses, but did not reduce HIV-1 VL, impact CD4+ T-cells count, delay ART initiation, or prevent HIV-1 related clinical events. PMID:26871794

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial.

PubMed

Dinges, Warren; Girard, Pierre-Marie; Podzamczer, Daniel; Brockmeyer, Norbert H; García, Felipe; Harrer, Thomas; Lelievre, Jean-Daniel; Frank, Ian; Colin De Verdière, Nathalie; Yeni, Guy-Patrick; Ortega Gonzalez, Enrique; Rubio, Rafael; Clotet Sala, Bonaventura; DeJesus, Edwin; Pérez-Elias, Maria Jesus; Launay, Odile; Pialoux, Gilles; Slim, Jihad; Weiss, Laurence; Bouchaud, Olivier; Felizarta, Franco; Meurer, Anja; Raffi, François; Esser, Stefan; Katlama, Christine; Koletar, Susan L; Mounzer, Karam; Swindells, Susan; Baxter, John D; Schneider, Stefan; Chas, Julie; Molina, Jean-Michel; Koutsoukos, Marguerite; Collard, Alix; Bourguignon, Patricia; Roman, François

2016-02-01

The impact of the investigational human immunodeficiency virus type 1 (HIV-1) F4/AS01B vaccine on HIV-1 viral load (VL) was evaluated in antiretroviral therapy (ART)-naive HIV-1 infected adults.This phase IIb, observer-blind study (NCT01218113), included ART-naive HIV-1 infected adults aged 18 to 55 years. Participants were randomized to receive 2 (F4/AS01B_2 group, N = 64) or 3 (F4/AS01B_3 group, N = 62) doses of F4/AS01B or placebo (control group, N = 64) at weeks 0, 4, and 28. Efficacy (HIV-1 VL, CD4 T-cell count, ART initiation, and HIV-related clinical events), safety, and immunogenicity (antibody and T-cell responses) were evaluated during 48 weeks.At week 48, based on a mixed model, no statistically significant difference in HIV-1 VL change from baseline was demonstrated between F4/AS01B_2 and control group (0.073 log10 copies/mL [97.5% confidence interval (CI): -0.088; 0.235]), or F4/AS01B_3 and control group (-0.096 log10 copies/mL [97.5% CI: -0.257; 0.065]). No differences between groups were observed in HIV-1 VL change, CD4 T-cell count, ART initiation, or HIV-related clinical events at intermediate timepoints. Among F4/AS01B recipients, the most frequent solicited symptoms were pain at injection site (252/300 doses), fatigue (137/300 doses), myalgia (105/300 doses), and headache (90/300 doses). Twelve serious adverse events were reported in 6 participants; 1 was considered vaccine-related (F4/AS01B_2 group: angioedema). F4/AS01B induced polyfunctional F4-specific CD4 T-cells, but had no significant impact on F4-specific CD8 T-cell and anti-F4 antibody levels.F4/AS01B had a clinically acceptable safety profile, induced F4-specific CD4 T-cell responses, but did not reduce HIV-1 VL, impact CD4 T-cells count, delay ART initiation, or prevent HIV-1 related clinical events.

Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries.

PubMed

del Amo, Julia; Moreno, Santiago; Bucher, Heiner C; Furrer, Hansjakob; Logan, Roger; Sterne, Jonathan; Pérez-Hoyos, Santiago; Jarrín, Inma; Phillips, Andrew; Lodi, Sara; van Sighem, Ard; de Wolf, Wolf; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Goulet, Joseph; Miró, José M; Ferrer, Elena; Meyer, Laurence; Seng, Rémonie; Toulomi, Giota; Gargalianos, Panagiotis; Costagliola, Dominique; Abgrall, Sophie; Hernán, Miguel A

2012-05-01

The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries. The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting. Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL. Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

A microchip CD4 counting method for HIV monitoring in resource-poor settings.

PubMed

Rodriguez, William R; Christodoulides, Nicolaos; Floriano, Pierre N; Graham, Susan; Mohanty, Sanghamitra; Dixon, Meredith; Hsiang, Mina; Peter, Trevor; Zavahir, Shabnam; Thior, Ibou; Romanovicz, Dwight; Bernard, Bruce; Goodey, Adrian P; Walker, Bruce D; McDevitt, John T

2005-07-01

More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.

Deworming and the immune status of HIV positive pre-antiretroviral therapy individuals in Arba Minch, Chencha and Gidole hospitals, Southern Ethiopia.

PubMed

Abossie, Ashenafi; Petros, Beyene

2015-09-28

Helminths/HIV co-infections are very common in developing countries, especially in Africa. The effect of overlapping distribution of HIV and helminths becomes important because concomitant infection may exacerbate disease outcome of HIV infection. The study aimed at determining the effect of deworming on the immune status of helminth/HIV coinfected Pre-ART HIV patients attending three health institutions in Southern Ethiopia. 97 HIV-positive Pre-ART individuals were observed into 2 groups on the basis of helminth co-infection and no infection. Out of these, 66 study participants were helminths/HIV co-infected and the remaining 31 study participants were helminths (-)/HIV (+) control. Helminth/HIV co-infected participants CD4+ T-cell count was done at baseline, after 15 weeks and 6 months after antihelminthics treatment. Data were analyzed using SPSS version 16. Ascaris lumbricoides was the highest prevalent soil transmitted helminths in Pre-ART individuals in this study. CD4+ T-cell count in the Ascaris lumricoides/HIV co-infected was significantly higher (P = 0.05) and (P < 0.05) after 15 weeks and 6 months post-antihelminthics treatment respectively. Also, after antihelminthic therapy, the CD4+ T-cell count significantly increased (P < 0.005) in all treated helminth infections. The study showed that treatment of ascariasis had a significant effect on CD4+ T-cell count increase in the treated Pre-ART Ascaris lumbricoides/HIV co-infected individuals; whereas the same positive effect was not evident for other intestinal helminth parasites detected in the study. In conclusion, this finding on Ascaris lumbricoides-specific nature of immune interaction in helminth/HIV co-infection may partly explain the inconsistent reports on the role of intestinal helminths on progression of HIV infection to AIDS. Therefore, a well-designed longitudinal study on helminth species-specific HIV/helminth co-infection will be needed to fully establish the possible benefits of deworming in intestinal helminth/HIV co-infection.

Intracoronary injection of CD34-cells in chronic ischemic heart failure: 7 years follow-up of the DanCell study.

PubMed

Hansen, Morten; Nyby, Sebastian; Eifer Møller, Jacob; Videbæk, Lars; Kassem, Moustapha; Barington, Torben; Thayssen, Per; Diederichsen, Axel Cosmus Pyndt

2014-01-01

Seven years ago, the DanCell study was carried out to test the hypothesis of improvement in left ventricular ejection fraction (LVEF) following repeated intracoronary injections of autologous bone marrow-derived stem cells (BMSCs) in patients suffering from chronic ischemic heart failure. In this post hoc analysis, the long-term effect of therapy is assessed. 32 patients [mean age 61 (SD ± 9), 81% males] with systolic dysfunction (LVEF 33 ± 9%) received two repeated intracoronary infusions (4 months apart) of autologous BMSCs (1,533 ± 765 × 10(6) BMSCs including 23 ± 11 × 10(6) CD34(+) cells and 14 ± 7 × 10(6) CD133(+) cells). Patients were followed for 7 years and deaths were recorded. During follow-up, 10 patients died (31%). In univariate regression analysis, the total number of BMSCs, CD34(+) cell count and CD133(+) cell count did not significantly correlate with survival (hazard ratio: 0.999, 95% CI: 0.998-1.000, p = 0.24; hazard ratio: 0.94, 95% CI: 0.88-1.01, p = 0.10, and hazard ratio: 0.96, 95% CI: 0.87-1.07, p = 0.47, respectively). After adjustment for baseline variables in multivariate regression analysis, the CD34(+) cell count was significantly associated with survival (hazard ratio: 0.90, 95% CI: 0.82-1.00, p = 0.04). Intracoronary injections of a high number of CD34(+) cells may have a beneficial effect on chronic ischemic heart failure in terms of long-term survival.

Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy

PubMed Central

May, Margaret T.; Gompels, Mark; Delpech, Valerie; Porter, Kholoud; Orkin, Chloe; Kegg, Stephen; Hay, Phillip; Johnson, Margaret; Palfreeman, Adrian; Gilson, Richard; Chadwick, David; Martin, Fabiola; Hill, Teresa; Walsh, John; Post, Frank; Fisher, Martin; Ainsworth, Jonathan; Jose, Sophie; Leen, Clifford; Nelson, Mark; Anderson, Jane; Sabin, Caroline

2014-01-01

Objective: The objective of this study is to estimate life expectancies of HIV-positive patients conditional on response to antiretroviral therapy (ART). Methods: Patients aged more than 20 years who started ART during 2000–2010 (excluding IDU) in HIV clinics contributing to the UK CHIC Study were followed for mortality until 2012. We determined the latest CD4+ cell count and viral load before ART and in each of years 1–5 of ART. For each duration of ART, life tables based on estimated mortality rates by sex, age, latest CD4+ cell count and viral suppression (HIV-1 RNA <400 copies/ml), were used to estimate expected age at death for ages 20–85 years. Results: Of 21 388 patients who started ART, 961 (4.5%) died during 110 697 person-years. At start of ART, expected age at death [95% confidence interval (CI)] of 35-year-old men with CD4+ cell count less than 200, 200–349, at least 350 cells/μl was 71 (68–73), 78 (74–82) and 77 (72–81) years, respectively, compared with 78 years for men in the general UK population. Thirty-five-year-old men who increased their CD4+ cell count in the first year of ART from less than 200 to 200–349 or at least 350 cells/μl and achieved viral suppression gained 7 and 10 years, respectively. After 5 years on ART, expected age at death of 35-year-old men varied from 54 (48–61) (CD4+ cell count <200 cells/μl and no viral suppression) to 80 (76–83) years (CD4+ cell count ≥350 cells/μl and viral suppression). Conclusion: Successfully treated HIV-positive individuals have a normal life expectancy. Patients who started ART with a low CD4+ cell count significantly improve their life expectancy if they have a good CD4+ cell count response and undetectable viral load. PMID:24556869

Correlation of CD4 count with cariogenic oral flora indicators and dental caries in HIV-seropositive children undergoing antiretroviral therapy in Mangaluru, South India.

PubMed

Muraleedharan, Soumya; Panchmal, Ganesh Shenoy; Shenoy, Rekha P; Jodalli, Praveen; Sonde, Laxminarayan; Pasha, Imran

2018-05-01

The aim of the present study was to compare the association of CD4 count with cariogenic oral flora indicators and dental caries in HIV-seropositive children receiving antiretroviral therapy (ART). A descriptive study was conducted among HIV-seropositive children receiving ART at Snehasadan Camillian Care and Support Center HIV/AIDS in Mangaluru, India. Demographic details and r recent CD4 counts were recorded. For dental caries, the Decayed, Missing, Filled Teeth (DMFT)/decayed, missing, filled/decayed, extracted, filled index was used. Data were analyzed using SPSS version 22. Spearman's correlation was used to correlate CD4 count with dental caries and cariogenic oral flora indicators (mutans streptococci and lactobacilli). The study population comprised 35 patients. Dental caries prevalence was 54.1% in deciduous teeth and 41.2% in permanent teeth. Age and DMFT showed a significant, positive correlation; age and dmft showed a negative correlation (P < .05). A weak, negative correlation was found between age and Streptococcus mutans (S. mutans), and also CD4 count; S. mutans and CD4 count and dmft were not found to be statistically significant (P < .05). No statistically-significant correlation was found between CD4 count and cariogenic oral flora indicators in HIV-positive patients. The presence of a minimum number of restored teeth compared to decayed teeth suggests a lack of dental care being given to HIV-positive patients. © 2017 John Wiley & Sons Australia, Ltd.

A cross-sectional study of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/AIDS.

PubMed

Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Shen, Jiayin; Tangkai Qi; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Zeng, Yi; Lu, Hongzhou

2015-04-01

We conducted a cross-sectional study to determine the prevalence and risk factors of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/AIDS. One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients were enrolled between 2009 and 2010. Serum samples obtained from each individual were collected for complete blood count. Factors associated with the presence of leukopenia and thrombocytopenia were analyzed by multiple logistic regression. The overall prevalence of leukopenia and of thrombocytopenia was 33.2% and 15.6%, respectively. The prevalence of leukopenia was higher among females than among males (39.4% versus 31.2%). The prevalence of leukopenia increased with decreasing CD4 count (8.2%, 26.5%, 33.4%, and 41.5% among patients with CD4 count of ≥ 350, 200-349, 50-199, and < 50 cells/mm3 respectively). The prevalence of thrombocytopenia also showed an increasing trend with decreasing CD4 count (5.8%, 12.2%, 17.8%, and 17.5% among patients with CD4 count of ≥ 350, 200-349, 50-199, and < 50 cells/mm3, respectively). Logistic analysis showed that female sex, lower CD4 count, and Han ethnicity were significantly associated with an increased risk of leukopenia, and that lower CD4 count, and HIV transmission by blood were significantly associated with an increased risk of thrombocytopenia. The study reflects that leukopenia and thrombocytopenia are common among Chinese adults with newly diagnosed HIV/AIDS; and lower CD4 count is associated with an increased risk of both leukopenia and thrombocytopenia. We propose that a routine assessment of these parameters is necessary for timely and adequate clinical management.

Immuno-virological discordance and the risk of non-AIDS and AIDS events in a large observational cohort of HIV-patients in Europe.

PubMed

Zoufaly, Alexander; Cozzi-Lepri, Alessandro; Reekie, Joanne; Kirk, Ole; Lundgren, Jens; Reiss, Peter; Jevtovic, Djordje; Machala, Ladislav; Zangerle, Robert; Mocroft, Amanda; Van Lunzen, Jan

2014-01-01

The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated. Patients in EuroSIDA starting at least 1 new antiretroviral drug with CD4<350 cells/µl and viral load (VL)>500 copies/mL were followed-up from the first day of VL< = 50 copies/ml until a new fatal/non-fatal non-AIDS/AIDS event. Considered non-AIDS events included non-AIDS malignancies, pancreatitis, severe liver disease with hepatic encephalopathy (>grade 3), cardio- and cerebrovascular events, and end-stage renal disease. Patients were classified over time according to whether current CD4 count was above (non-ID) or below (ID) baseline level. Relative rates (RR) of events were calculated for ID vs. non-ID using adjusted Poisson regression models. 2,913 patients contributed 11,491 person-years for the analysis of non-AIDS. 241 pre-specified non-AIDS events (including 84 deaths) and 89 AIDS events (including 10 deaths) occurred. The RR of developing pre-specified non-AIDS events for ID vs. non-ID was 1.96 (95% CI 1.37-2.81, p<0.001) in unadjusted analysis and 1.43 (0.94-2.17, p = 0.095) after controlling for current CD4 count. ID was not associated with the risk of AIDS events (aRR 0.76, 95% CI 0.41-1.38, p = 0.361). Compared to CD4 responders, patients with immuno-virological discordance may be at increased risk of developing non-AIDS events. Further studies are warranted to establish whether in patients with ID, strategies to directly modify CD4 count response may be needed besides the use of ART.

A clinicopathological study of peripheral lymph nodes in HIV-infected patients with special reference to CD4+ T-cell counts: Experience from a tertiary care institution in Darjeeling (India).

PubMed

Mandal, Rupali; Mondal, Krishnendu; Datta, Saikat; Chakrabarti, Indranil; Giri, Amita; Goswami, Bidyut Krishna

2015-12-01

HIV/AIDS is a major health burden worldwide. India bears the third highest HIV-patients load globally. In the Darjeeling district, HIV-prevalence is >1% with very little known about the profile of HIV-lymphadenopathy. The aim of this study was to identify the different causes of peripheral lymphadenopathy among HIV-infected patients in this region, correlate them with CD4+ T-cell counts and formulate some common clinico-haematological parameters as potential predictors of CD4+ T-cell count. In the present study, 76 cases were evaluated. Fine Needle Aspiration Cytology (FNAC) was performed as an out-patient procedure in the Department of Pathology. Smears were stained routinely with Haematoxylin-Eosin and Leishman stains. ZN stains were done when indicated by the cytological findings. Immediate CD4+ T-cell count was obtained by referring the patients to the Anti-retroviral therapy centre. Cytological diagnoses included tuberculosis (82.9%), reactive hyperplasia (6.6%), nonspecific granulomatous lesions (3.9%), non-Hodgkin lymphoma (2.6%), histoplasmosis (2.6%) and simultaneous filariasis with toxoplasmosis (1.3%). Statistically, the opportunistic infections and lymphomas significantly concurred with a CD4+ T-cell count <350/μl. Likewise, the number of enlarged lymph nodes and absolute lymphocyte count (ALC) were found to be useful predictors of CD4+ T-cell counts. Lymph node cytology in HIV-infected patients is essential to identify opportunistic infections from neoplastic lesions and; to enable therapeutic strategies. Correlation of lesions with mean CD4+ T-cell count predicts personal immunity, stage of disease and disease activity. Furthermore, enlarged lymph node numbers and ALC can be surrogate markers of CD4+ T-cell count for monitoring the severity of the immune suppression in under-resourced countries like India. © 2015 Wiley Periodicals, Inc.

Different degree of immune recovery using antiretroviral regimens with Vonavir or Zidovudine/Lamivudine and Efavirenz in Patients receiving first line treatment in Iran.

PubMed

Sadeghi, Leila; Moallemi, Samaneh; Tabatabai, Reza Adl; Esmaeilzadeh, Ali; Ahsani-Nasab, Sara; Ahmadi, Niloofar Eghbal; Bayanolhagh, Saeed; Lolaie, Mahin; Narouei, Arsalan; Alinaghi, Ahmad; Mohraz, Minoo

2018-01-07

The initial ART regimens used by most national treatment guidelines in resource-limited settings include 2 nucleoside reverse-transcriptase inhibitors (NRTIs) and 1 non-nucleoside reverse-transcriptase inhibitor (NNRTI). The NRTIshave consistedof Zidovudine (AZT) or Stavudine (d4T) with Lamivudine (3TC); the NNRTI component hasbeen Nevirapine (NVP) or Efavirenz (EFV). There exists few data indicating if Vonavir is more effective in increasing CD4+ T cell counts or other first-line drugs of ART.Immunological outcomes of 134 individuals who just started antiretroviral therapy with Vonavir or Zidovudine/Lamivudine and Efavirenzanalyzed. Immunological response was then assessed during 28 weeks and indicated significant CD4+ T cell increase in both groups. The increase in CD4+ T cell counts was greater in Zidovudine/Lamivudine and Efavirenz treated group. A rapid CD4+ T cell increase occurred after the first 12 weeks of therapy in Vonavir treated group with initial CD4+ T cell counts ≤100 despite the individuals with higher CD4+ T cell counts. As previous studies, we observed the noticeable increase rate of CD4+ Tcells is in the first three months of therapy. A rapid CD4+ Tcell increase occurred shortly after beginning anti retroviraltherapy using either Vonaviror Zidovudine/Lamivudine and Efavirenz. Late increases in CD4+ T cell counts are more pronounced in therapy using Zidovudine/Lamivudine and Efavirenz. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A declining CD4 count and diagnosis of HIV-associated Hodgkin lymphoma: do prior clinical symptoms and laboratory abnormalities aid diagnosis?

PubMed

Gupta, Ravindra K; Marks, Michael; Edwards, Simon G; Smith, Katie; Fletcher, Katie; Lee, Siow-Ming; Ramsay, Alan; Copas, Andrew J; Miller, Robert F

2014-01-01

The incidence of Hodgkin lymphoma (HL) among HIV-infected individuals remains unchanged since the introduction of combination antiretroviral therapy (cART). Recent epidemiological data suggest that CD4 count decline over a year is associated with subsequent diagnosis of HL. In an era of economic austerity monitoring the efficacy of cART by CD4 counts may no longer be required where CD4 count>350 cells/µl and viral load is suppressed (<50 copies/ml). We sought to establish among our HIV outpatient cohort whether a CD4 count decline prior to diagnosis of HL, whether any decline was greater than in patients without the diagnosis, and also whether other clinical or biochemical indices were reliably associated with the diagnosis. Twenty-nine patients with a diagnosis of HL were identified. Among 15 individuals on cART with viral load <50 copies/ml the change in CD4 over 12 months preceding diagnosis of HL was -82 cells/µl (95% CI -163 to -3; p = 0.04). Among 18 matched controls the mean change was +5 cells/µl, 95% CI -70 to 80, p = 0.89). The decline in CD4 over the previous 6-12 months was somewhat greater in cases than controls (mean difference in change -55 cells/µl, 95% CI -151 to 39; p = 0.25). In 26 (90%) patients B symptoms had been present for a median of three months (range one-12) before diagnosis of HL. The CD4 count decline in the 12 months prior to diagnosis of Hodgkin lymphoma among HIV-infected individuals with VL<50 copies/ml on cART was not significantly different from that seen in other fully virologically suppressed individuals in receipt of cART and who did not develop HL. All those who developed HL had B symptoms and/or new palpable lymphadenopathy, suggesting that CD4 count monitoring if performed less frequently, or not at all, among those virologically suppressed individuals with CD4 counts >350 may not have delayed diagnosis.

Early mortality among children and adults in antiretroviral therapy programs in Southwest Ethiopia, 2003-15.

PubMed

Gesesew, Hailay Abrha; Ward, Paul; Woldemichael, Kifle; Mwanri, Lillian

2018-01-01

Several studies reported that the majority of deaths in HIV-infected people are documented in their early antiretroviral therapy (ART) follow-ups. Early mortality refers to death of people on ART for follow up period of below 24 months due to any cause. The current study assessed predictors of early HIV mortality in Southwest Ethiopia. We have conducted a retrospective analysis of 5299 patient records dating from June 2003- March 2015. To estimate survival time and compare the time to event among the different groups of patients, we used a Kaplan Meir curve and log-rank test. To identify mortality predictors, we used a cox regression analysis. We used SPSS-20 for all analyses. A total of 326 patients died in the 12 years follow-up period contributing to 6.2% cumulative incidence and 21.7 deaths per 1000 person-year observations incidence rate. Eighty-nine percent of the total deaths were documented in the first two years follow up-an early-term ART follow up. Early HIV mortality rates among adults were 50% less in separated, divorced or widowed patients compared with never married patients, 1.6 times higher in patients with baseline CD4 count <200 cells/μL compared to baseline CD4 count ≥200 cells/μL, 1.5 times higher in patients with baseline WHO clinical stage 3 or 4 compared to baseline WHO clinical stage 1 or 2, 2.1 times higher in patients with immunologic failure compared with no immunologic failure, 60% less in patients with fair or poor compared with good adherence, 2.9 times higher in patients with bedridden functional status compared to working functional status, and 2.7 times higher with patients who had no history of HIV testing before diagnosis compared to those who had history of HIV testing. Most predictors of early mortality remained the same to the predictors of an overall HIV mortality. When discontinuation was assumed as an event, the predictors of an overall HIV mortality included age between 25-50 years, base line CD4 count, developing immunologic failure, bedridden functional status, and no history of HIV testing before diagnosis. The great majority of deaths were documented in the first two years of ART, and several predictors of early HIV mortality were also for the overall mortality when discontinuation was assumed as event or censored. Considering the above population, interventions to improve HIV program in the first two years of ART follow up should be improved.

Ocular Manifestations of Acquired Immunodeficiency Syndrome.

PubMed

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong; Lee, Sung Jin

2015-08-01

To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular manifestations. We found that CD4+ count and age >35 years were independent risk factors for developing ocular manifestations.

Ocular Manifestations of Acquired Immunodeficiency Syndrome

PubMed Central

Kim, Young Shin; Sun, Hae Jung; Kim, Tae Hyong; Kang, Kui Dong

2015-01-01

Purpose To investigate the patterns and risk factors of the ocular manifestations of acquired immunodeficiency syndrome (AIDS) and their correlation with CD4+ count in the era of highly active antiretroviral therapy (HAART). Methods This retrospective study examined 127 AIDS patients who presented to Soonchunhyang University Hospital. Data were collected from patient interviews, clinical examinations, and laboratory investigations. Ophthalmologic examinations included the best-corrected visual acuity, intraocular pressure, anterior segment and adnexal examination, and dilated fundus examination. Results Of the 127 patients with AIDS, 118 were on HAART and 9 were not. The mean CD4+ count was 266.7 ± 209.1 cells/µL. There were ocular manifestations in 61 patients (48.0%). The incidence of anterior segment manifestations was higher than posterior segment manifestations at 28.3% and 19.7%, respectively. The mean CD4+ count was significantly (p < 0.05) lower in the patients with posterior versus anterior segment ocular manifestations. The most common ocular manifestation was retinal microvasculopathy (15.0%), followed by keratoconjunctivitis sicca (14.2%), conjunctival microvasculopathy (9.4%), cytomegalovirus retinitis (3.1%), herpes zoster ophthalmicus (2.4%), and blepharitis (1.6%). Retinal microvasculopathy and cytomegalovirus retinitis were common in patients with CD4+ counts <200 cells/µL, while keratoconjunctivitis sicca and conjunctival microvasculopathy were common in patients with CD4+ counts of 200 to 499 cells/µL. There was a significant (p < 0.05) association between ocular manifestation and CD4+ count or age. Conclusions The introduction of HAART has changed the landscape of ocular presentations in patients with AIDS. In this study, anterior segment and external ocular manifestations occurred more frequently than posterior segment manifestations. Also, the mean CD4+ count was significantly lower in patients with posterior segment ocular manifestations versus anterior segment ocular manifestations. We found that CD4+ count and age >35 years were independent risk factors for developing ocular manifestations. PMID:26240508

Depression and Anxiety are Common in Acute HIV Infection and Associate with Plasma Immune Activation.

PubMed

Hellmuth, Joanna; Colby, Donn; Valcour, Victor; Suttichom, Duanghathai; Spudich, Serena; Ananworanich, Jintanat; Prueksakaew, Peeriya; Sailasuta, Napapon; Allen, Isabel; Jagodzinski, Linda L; Slike, Bonnie; Ochi, Derek; Paul, Robert

2017-11-01

This observational study of 123 Thai participants sought to determine the rate and severity of affective symptoms during acute HIV infection (AHI) and possible associations to disease mechanisms. At diagnosis, just prior to starting combination antiretroviral therapy (cART), AHI participants completed assessments of depression and anxiety symptoms that were repeated at 4, 12, and 24 weeks. Blood markers of HIV infection and immune activation were measured at study entry, with optional cerebrospinal fluid measures. A high frequency of participants reported symptoms that exceeded published thresholds supportive of depression (55.0%) and anxiety (65.8%) at diagnosis, with significant reductions after starting cART. Meeting a threshold for clinically relevant depressive symptoms at study entry was associated with higher baseline plasma HIV RNA (5.98 vs. 5.50, t = 2.46, p = 0.015), lower CD4 counts (328 vs. 436 cells/mm 3 , t = 3.46, p = 0.001), and higher plasma neopterin, a marker of macrophage activation (2694 vs. 1730 pg/mL, Mann-Whitney U = 152.5, p = 0.011). Controlling for plasma HIV RNA and CD4 count, higher baseline plasma neopterin correlated with worse initial depression and anxiety scores. Depression and anxiety symptoms are frequent in acute HIV infection, associate with plasma immune activation, and can improve concurrent with cART.

Structured intermittent interruption of chronic HIV infection treatment with highly active antiretroviral therapy: effects on leptin and TNF-alpha.

PubMed

Arjona, M Montes de Oca; Pérez-Cano, R; Garcia-Juárez, R; Martín-Aspas, A; del Alamo, C Fernández Gutiérrez; Girón-González, J A

2006-04-01

The changes in nutritional parameters and adipocytokines after structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection are analyzed. Twenty-seven patients with chronic HIV infection (median CD4+ T cell count/microl: nadir, 394; at the beginning of structured interruptions, 1041; HIV viral load: nadir, 41,521 copies/ml; at the beginning of structured interruptions <50 copies/ml; median time of previous treatment: 60 months) were evaluated during three cycles of intermittent interruptions of therapy (8 weeks on/4 weeks off). CD4+ T cell count, HIV viral load, anthropometric measures, and serum concentrations of triglycerides, cholesterol, leptin, and tumor necrosis factor and its soluble receptors I and II were determined. After the three cycles of intermittent interruptions of therapy, no significant differences in CD4+ T cell count/microl, viral load, or serum concentrations of cholesterol or triglycerides with reference to baseline values were found. A near-significant higher fatty mass (skinfold thicknesses, at the end, 121 mm, at the beginning, 100 mm, p = 0.100), combined with a significant increase of concentration of leptin (1.5 vs. 4.7 ng/ml, p = 0,044), as well as a decrease in serum concentrations of soluble receptors of tumor necrosis factor (TNFRI, 104 vs. 73 pg/ml, p = 0.022; TNFRII 253 vs. 195 pg/ml, p = 0.098) were detected. Structured intermittent interruption of highly active antiretroviral treatment of patients with chronic HIV infection induces a valuable positive modification in markers of lipid turnover and adipose tissue mass.

Effects of high CD4 cell counts on death and attrition among HIV patients receiving antiretroviral treatment: an observational cohort study.

PubMed

Tang, Zhenzhu; Pan, Stephen W; Ruan, Yuhua; Liu, Xuanhua; Su, Jinming; Zhu, Qiuying; Shen, Zhiyong; Zhang, Heng; Chen, Yi; Lan, Guanghua; Xing, Hui; Liao, Lingjie; Feng, Yi; Shao, Yiming

2017-06-09

Current WHO guidelines recommend initiating ART regardless of CD4+ cell count. In response, we conducted an observational cohort study to assess the effects of pre-ART CD4+ cell count levels on death, attrition, and death or attrition in HIV treated patients. This large HIV treatment cohort study (n = 49,155) from 2010 to 2015 was conducted in Guangxi, China. We used a Cox regression model to analyze associations between pre-ART CD4+ cell counts and death, attrition, and death or attrition. The average mortality and ART attrition rates among all treated patients were 2.63 deaths and 5.32 attritions per 100 person-years, respectively. Compared to HIV patients with <350 CD4+ cells/mm 3 at ART initiation, HIV patients with >500 CD4+ cells/mm 3 at ART initiation had a significantly lower mortality rate (Adjusted hazard ratio: 0.56, 95% CI: 0.40-0.79), but significantly higher ART attrition rate (AHR: 1.17, 95% CI: 1.03-1.33). Results from this study suggest that HIV patients with high CD4+ cell counts at the time of ART initiation may be at greater risk of treatment attrition. To further reduce ART attrition, it is imperative that patient education and healthcare provider training on ART adherence be enhanced and account for CD4 levels at ART initiation.

Quantification of Cells with Specific Phenotypes I: Determination of CD4+ Cell Count Per Microliter in Reconstituted Lyophilized Human PBMC Prelabeled with Anti-CD4 FITC Antibody

PubMed Central

Stebbings, Richard; Wang, Lili; Sutherland, Janet; Kammel, Martin; Gaigalas, Adolfas K; John, Manuela; Roemer, Bodo; Kuhne, Maren; Schneider, Rudolf J; Braun, Michael; Engel, Andrea; Dikshit, Dinesh K; Abbasi, Fatima; Marti, Gerald E; Paola Sassi, Maria; Revel, Laura; Kim, Sook-Kyung; Baradez, Marc-Olivier; Lekishvili, Tamara; Marshall, Damian; Whitby, Liam; Jing, Wang; Ost, Volker; Vonsky, Maxim; Neukammer, Jörg

2015-01-01

A surface-labeled lyophilized lymphocyte (sLL) preparation has been developed using human peripheral blood mononuclear cells prelabeled with a fluorescein isothiocyanate conjugated anti-CD4 monoclonal antibody. The sLL preparation is intended to be used as a reference material for CD4+ cell counting including the development of higher order reference measurement procedures and has been evaluated in the pilot study CCQM-P102. This study was conducted across 16 laboratories from eight countries to assess the ability of participants to quantify the CD4+ cell count of this reference material and to document cross-laboratory variability plus associated measurement uncertainties. Twelve different flow cytometer platforms were evaluated using a standard protocol that included calibration beads used to obtain quantitative measurements of CD4+ T cell counts. There was good overall cross-platform and counting method agreement with a grand mean of the laboratory calculated means of (301.7 ± 4.9) μL−1 CD4+ cells. Excluding outliers, greater than 90% of participant data agreed within ±15%. A major contribution to variation of sLL CD4+ cell counts was tube to tube variation of the calibration beads, amounting to an uncertainty of 3.6%. Variation due to preparative steps equated to an uncertainty of 2.6%. There was no reduction in variability when data files were centrally reanalyzed. Remaining variation was attributed to instrument specific differences. CD4+ cell counts obtained in CCQM-P102 are in excellent agreement and show the robustness of both the measurements and the data analysis and hence the suitability of sLL as a reference material for interlaboratory comparisons and external quality assessment. © 2015 The Authors. Published by Wiley Periodicals, Inc. PMID:25655255

The effect of probiotics on CD4 counts among people living with HIV: a systematic review.

PubMed

Miller, H; Ferris, R; Phelps, B R

2016-06-01

Probiotics are defined by the WHO as 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. Ongoing research has shown probiotics provide benefits to humans, including protection and restoration of the gastrointestinal and other mucosal tracts. As human immunodeficiency virus (HIV) activates gut-associated lymphoid tissue (GALT), several studies have investigated the effect of probiotics on CD4 cell count and related outcomes among those living with HIV. These studies are summarised here. Manuscripts were identified using the search terms 'probiotics', 'synbiotics', 'HIV', and 'CD4', and were reviewed for relevance and inclusion of CD4 count as an immunologic endpoint. Bibliographies of relevant manuscripts were also reviewed for additional studies matching inclusion and exclusion criteria. The search yielded 91 results; 13 included relevant outcomes. Seven of these studies produced beneficial CD4 outcomes, while the remaining 6 reported on insignificant beneficial or negative CD4 outcomes. The studies summarised here collectively suggest that daily consumption of probiotics over a prolonged period of time may improve CD4 count in people living with HIV.

Predictive factors for long-term engraftment of autologous blood stem cells.

PubMed

Duggan, P R; Guo, D; Luider, J; Auer, I; Klassen, J; Chaudhry, A; Morris, D; Glück, S; Brown, C B; Russell, J A; Stewart, D A

2000-12-01

Data from 170 consecutive patients aged 19-66 years (median age 46 years) who underwent unmanipulated autologous blood stem cell transplant (ASCT) were analyzed to determine if total CD34+ cells/kg infused, CD34+ subsets (CD34+41+, CD34+90+, CD34+33-, CD34+38-, CD34+38-DR-), peripheral blood CD34+ cell (PBCD34+) count on first apheresis day, or various clinical factors were associated with low blood counts 6 months post ASCT. Thirty-four patients were excluded from analysis either because of death (n = 17) or re-induction chemotherapy prior to 6 months post ASCT (n = 13), or because of lack of follow-up data (n = 4). Of the remaining 136 patients, 46% had low WBC ( < 4 x 10(9)/l), 41% low platelets (<150 x 10(9)/l), and 34% low hemoglobin ( < 120 g/l) at a median of 6 months following ASCT. By Spearman's rank correlation, both the total CD34+ cell dose/kg and the PBCD34+ count correlated with 6 month blood counts better than any subset of CD34+ cells or any clinical factor. The PBCD34+ count was overall a stronger predictor of 6 month blood counts than was the total CD34+ cells/kg infused. Both factors retained their significance in multivariate analysis, controlling for clinical factors. In conclusion, subsets of CD34+ cells and clinical factors are inferior to the total CD34+ cell dose/kg and PBCD34+ count in predicting 6 month blood counts following ASCT.

Reconstruction of the immune system after unrelated or partially matched T-cell-depleted bone marrow transplantation in children: immunophenotypic analysis and factors affecting the speed of recovery.

PubMed

Kook, H; Goldman, F; Padley, D; Giller, R; Rumelhart, S; Holida, M; Lee, N; Peters, C; Comito, M; Huling, D; Trigg, M

1996-08-01

We prospectively studied immune reconstitution in 102 children who underwent T-lymphocyte depleted bone marrow transplants using either closely matched unrelated donors or partially matched familial donors by assaying total lymphocyte counts (TLC), T-cell subsets, B cells, and natural killer cells. TLC, CD3+, and CD4+ T-cell counts remained depressed until 2 to 3 years posttransplant, whereas CD8+ T-cell counts normalized by 18 months, resulting in an inverted CD4:CD8 ratio until 12 months posttransplant. Although the percentage of NK cells was elevated early posttransplant, their absolute numbers remained normal. CD20+ B cells were depressed until 12 to 18 months posttransplant. Factors affecting immunophenotypic recovery were analyzed by nonparametric statistics. Younger patients tended to have higher TLC posttransplant. Higher marrow cell doses were not associated with hastened immunophenotypic recovery. Graft-versus-host disease (GVHD) and/or its treatment significantly delayed the immune reconstitution of CD3+, CD4+, and CD20+ cells. The presence of cytomegalovirus was associated with increased CD8+ counts and a decrease in the percentages of CD4+ and CD20+ cells.

Association between red blood cell indices and CD4 count in HIV-positive reproductive women

NASA Astrophysics Data System (ADS)

Lumbanraja, S. N.; Siregar, D. I. S.

2018-03-01

Red blood cell indices, hemoglobin, and hematocrit reflect rapidity of HIV disease progression. This study aims to determine red blood cell indices and CD4 count in HIV-positive reproductive women. This study was a cross sectional study conducted at AIDS outpatient clinic at Haji Adam Malik General Hospital, Medan Indonesia. All seropositive reproductive women within antiretroviral therapy consented for blood count and CD4 examination. Data were collected and analyzed with SPSS 19. In subjects with CD4≤350 mm3, mean hemoglobin was 10.95 ± 2.01, hematocrit was 31.83 ± 5.04%, MCV was 84.17 ± 11.41, MCH was 25.98 ± 2.65, and MCHC was 32.18 ± 2.17. Mean hemoglobin, hematocrit, and MCH value was significantly lower in subjects with CD4 ≤350 mm3 (p=0.014; p=0.001; p=0.01; respectively). Lower Hb, Ht, and MCH associated with thelower CD4 count.

[CD4 lymphocytopenia in systemic lupus erythematosus].

PubMed

Ferreira, Sofia; Vasconcelos, Júlia; Marinho, António; Farinha, Fátima; Almeida, Isabel; Correia, João; Barbosa, Paulo; Mendonça, Teresa; Vasconcelos, Carlos

2009-01-01

Systemic Lupus Erythematosus (SLE) is an inflammatory chronic disease characterized by the presence of autoantibodies, immunocomplex production and organ injury. Several alterations of the immune system have been described, namely of CD4 T cells, with particular focus on regulatory subgroup. Quantify peripheral CD4 T cells in a population of patients with SLE and correlate it with lupus activity, affected organs, therapeutics and infections. Retrospective study involving all SLE patients seen in the clinical immunology outpatient clinic of the Hospital Geral Santo António, Porto that has done some peripheral blood flow cytometry study. Twenty-nine patients have been evaluated, 16 were taking glucocorticoids and six immunossupressors. The mean SLEDAI at the study time was nine and the ECLAM was three. Thirty-one percent of the patients had leukopenia, 76% lymphocytopenia and the same number CD4 depletion. Fifty-five percent of the patients had CD4 levels lower than 500/mm3, 31% lower than 200/mm3. All patients with SLEDAI > or = 20 and ECLAM > or = 4 had CD4 counts inferior to 500/mm3 and all patients with inactive disease had CD4 superior to 500/mm3. There have been three opportunistic infections: cryptococcal meningitis, pulmonary aspergilosis, Pneumocystis jirovecii pneumonia, all in patients with CD4 counts lower than 500/mm3. Decreased CD4 T cells counts have been very common in this study population. There is an inverse relation between CD4 cells counts and disease activity. Opportunistic infections occurred in patients with severe CD4 depletion.

Safety of nevirapine in HIV-infected pregnant women initiating antiretroviral therapy at higher CD4 counts: a systematic review and meta-analysis.

PubMed

Bera, Ebrahim; Mia, Rafiq

2012-10-08

The package insert for nevirapine (NVP) cautions use in HIV-infected women (including pregnant women) with CD4 counts ≥250 cells/µl. However, recent studies showed that the CD4 count of pregnant women receiving antiretroviral therapy (ART) was not predictive of NVP toxicity. To determine whether ART-naive pregnant women initiating NVP-based ART at higher CD4 counts experience greater toxicity compared with pregnant women at lower CD4 counts. We reviewed studies comparing serious adverse NVP-related events among ART-naive pregnant women who commenced therapy at higher v. lower CD4 counts. Relevant studies were extracted from PubMed, SCOPUS and EMBASE, major journals and conference proceedings prior to December 2011. Authors were contacted for additional data. Data were independently extracted and entered into Review Manager. Fourteen studies (2 663 participants) were included for analysis. The odds ratio (OR) for overall NVP toxicity among pregnant women with CD4 <250 cells/µl was 0.61 (95% confidence interval (CI) 0.43 - 0.85). When analysis was restricted to prospective studies only (7 studies, 1 318 participants), the results were consistent for overall NVP toxicity (OR 0.43; 95% CI 0.25 - 0.73) and severe hepatotoxicity (OR 0.45; 95% CI 0.22 - 0.90), but not for severe cutaneous reaction (OR 0.53; 95% CI 0.26 - 1.10). Initiating NVP-based ART during pregnancy at CD4 ≥250 cells/µl increases toxicity risk and should be avoided, necessitating urgent revision of current guidelines supporting this practice.

Changes in hematological indices and lymphocyte subsets in response to whole blood donation in healthy male donors.

PubMed

Borai, Anwar; Livingstone, Callum; Alsobhi, Enaam; Al Sofyani, Abeer; Balgoon, Dalal; Farzal, Anwar; Almohammadi, Mohammed; Al-Amri, Abdulafattah; Bahijri, Suhad; Alrowaili, Daad; Bassiuni, Wafaa; Saleh, Ayman; Alrowaili, Norah; Abdelaal, Mohamed

2017-04-01

Whole blood donation has immunomodulatory effects, and most of these have been observed at short intervals following blood donation. This study aimed to investigate the impact of whole blood donation on lymphocyte subsets over a typical inter-donation interval. Healthy male subjects were recruited to study changes in complete blood count (CBC) (n = 42) and lymphocyte subsets (n = 16) before and at four intervals up to 106 days following blood donation. Repeated measures ANOVA were used to compare quantitative variables between different visits. Following blood donation, changes in CBC and erythropoietin were as expected. The neutrophil count increased by 11.3% at 8 days (p < .001). Novel changes were observed in lymphocyte subsets as the CD4/CD8 ratio increased by 9.2% (p < .05) at 8 days and 13.7% (p < .05) at 22 days. CD16-56 cells decreased by 16.2% (p < .05) at 8 days. All the subsets had returned to baseline by 106 days. Regression analysis showed that the changes in CD16-56 cells and CD4/CD8 ratio were not significant (Wilk's lambda = 0.15 and 0.94, respectively) when adjusted for BMI. In conclusion, following whole blood donation, there are transient changes in lymphocyte subsets. The effect of BMI on lymphocyte subsets and the effect of this immunomodulation on the immune response merit further investigation.

Correlation of mucocutaneous manifestations of HIV-infected patients in an ART center with CD4 counts.

PubMed

Lahoti, Sonal; Rao, Kavita; Umadevi, H S; Mishra, Lakshmi

2017-01-01

As the search for reliable clinical indicators for management of human immunodeficiency virus/AIDS continues, mucocutaneous manifestations of HIV are considered among key clinical indicators for prediction of underlying degree of immunosuppression, systemic opportunistic infections, and disease progression. (1) To study the prevalence of mucocutaneous manifestations in HIV-seropositive patients attending the ART center of our hospital (2) To correlate mucocutaneous manifestations with CD4 cell counts. A total of 200 HIV-seropositive patients of adult age group visiting our hospital were included in the study. Information on demographics such as age, sex, transmission route, socioeconomic status, educational status, CD4 counts, and mucocutaneous findings was collected through interview administered survey and case records followed by oral and cutaneous examination. Mean CD4 cell count of asymptomatic HIV/AIDS patients was 580.96 cells/mm3. In comparison with the CD4 cell count of asymptomatic HIV-positive patients, (mean 580.96 cells/mm3) CD4 cell count of HIV-positive patients with various mucocutaneous manifestations (mean 409.65 cells/mm3) was correlated using student t-test and was statistically significant (P = 0.017). This study revealed maximum mucocutaneous lesions in the CD4 count range of 200-500. Nail changes accounted for the most common cutaneous manifestation with 53%, and pigmentation accounted for the most common oral manifestation with 39%. Mucocutaneous manifestations can arouse one to suspect the diagnosis of HIV infection in an otherwise healthy unwary patient. They can serve as a dependable marker of HIV disease.

Mean CD4 cell count changes in patients failing a first-line antiretroviral therapy in resource-limited settings

PubMed Central

2012-01-01

Background Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. Method Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. Results 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/μL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. Conclusion In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART. PMID:22742573

Mortality in members of HIV-1 serodiscordant couples in Africa and implications for antiretroviral therapy initiation: Results of analyses from a multicenter randomized trial

PubMed Central

2012-01-01

Background The risk of HIV-1 related mortality is strongly related to CD4 count. Guidance on optimal timing for initiation of antiretroviral therapy (ART) is still evolving, but the contribution of HIV-1 infection to excess mortality at CD4 cell counts above thresholds for HIV-1 treatment has not been fully described, especially in resource-poor settings. To compare mortality among HIV-1 infected and uninfected members of HIV-1 serodiscordant couples followed for up to 24 months, we conducted a secondary data analysis examining mortality among HIV-1 serodiscordant couples participating in a multicenter, randomized controlled trial at 14 sites in seven sub-Saharan African countries. Methods Predictors of death were examined using Cox regression and excess mortality by CD4 count and plasma HIV-1 RNA was computed using Poisson regression for correlated data. Results Among 3295 HIV serodiscordant couples, we observed 109 deaths from any cause (74 deaths among HIV-1 infected and 25 among HIV-1 uninfected persons). Among HIV-1 infected persons, the risk of death increased with lower CD4 count and higher plasma viral levels. HIV-1 infected persons had excess mortality due to medical causes of 15.2 deaths/1000 person years at CD4 counts of 250 – 349 cells/μl and 8.9 deaths at CD4 counts of 350 – 499 cells/μl. Above a CD4 count of 500 cells/μl, mortality was comparable among HIV-1 infected and uninfected persons. Conclusions Among African serodiscordant couples, there is a high rate of mortality attributable to HIV-1 infection at CD4 counts above the current threshold (200 – 350 cells/μl) for ART initiation in many African countries. These data indicate that earlier initiation of treatment is likely to provide clinical benefit if further expansion of ART access can be achieved. Trial Registration Clinicaltrials.gov (NCT00194519) PMID:23130818

The effect of incident tuberculosis on immunological response of HIV patients on highly active anti-retroviral therapy at the university of Gondar hospital, northwest Ethiopia: a retrospective follow-up study.

PubMed

Assefa, Abate; Gelaw, Baye; Getnet, Gebeyaw; Yitayew, Gashaw

2014-08-27

Human immunodeficiency virus (HIV) infection is usually complicated by high rates of tuberculosis (TB) co-infection. Impaired immune response has been reported during HIV/TB co-infection and may have significant effect on anti-retroviral therapy (ART). TB/HIV co - infection is a major public health problem in Ethiopia. Therefore, the aim of the study was to assess the effect of TB incidence on immunological response of HIV patients during ART. A retrospective follow-up study was conducted among adult HIV patients who started ART at the University of Gondar Hospital. Changes in CD4+ T - lymphocyte count and incident TB episodes occurring during 42 months of follow up on ART were assessed. Life table was used to estimate the cumulative immunologic failure. Kaplan-Meier curve was used to compare survival curves between the different categories. Cox-proportional hazard model was employed to examine predictors of immunological failure. Among 400 HIV patients, 89(22.2%) were found to have immunological failure with a rate of 8.5 per 100 person-years (PY) of follow-up. Incident TB developed in 26(6.5%) of patients, with an incidence rate of 2.2 cases per 100 PY. The immunological failure rate was high (20.1/100PY) at the first year of treatment. At multivariate analysis, Cox regression analysis showed that baseline CD4+ T - cell count <100 cells/mm3 (adjusted hazard ratio (AHR) 1.8; 95%CI: 1.10 - 2.92, p = 0.023) and being male sex (AHR 1.6; 95%CI: 1.01 - 2.68, p = 0.046) were found to be significant predictors of immunological failure. There was borderline significant association with incident TB (AHR 2.2; 95%CI: 0.94 - 5.09, p = 0.06). The risk of immunological failure was significantly higher (38.5%) among those with incident TB compared with TB - free (21.1%) (Log rank p = 0.036). High incidence of immunological failure occurred within the first year of initiating ART. The proportions of patients with impaired immune restoration were higher among patients with incident TB. Lower baseline CD4+ T - cells count of <100 cells/mm3 and being male sex were significant predictors of immunological failure. The result highlighted the beneficial effects of earlier initiation of ART on CD4+ T - cell count recovery.

A Trial of a Single Tablet Regimen of Elvitegravir, Cobicistat, Emtricitabine, and Tenofovir Disoproxil Fumarate for the Initial Treatment of HIV-2 Infection in a Resource-Limited Setting: 48 Week Results from Senegal, West Africa.

PubMed

Ba, Selly; Raugi, Dana N; Smith, Robert A; Sall, Fatima; Faye, Khadim; Hawes, Stephen E; Sow, Papa Salif; Seydi, Moussa; Gottlieb, Geoffrey S

2018-04-17

There is an urgent need for safe and effective ART for HIV-2 infection. We undertook the first clinical trial of a single-tablet-regimen containing elvitegravir-cobicistat-emtricitabine-tenofovir disoproxil fumarate (E/C/F/TDF) to assess its effectiveness in HIV-2-infected individuals in Senegal, West Africa. HIV-2-infected, ART-naïve adults with WHO stage 3-4 disease or CD4 counts below 750 cells/mm3 were eligible for this 48 week, open-label trial. We analyzed HIV-2 viral loads (VL), CD4 counts, clinical and adverse events, mortality and loss-to-follow-up. We enrolled 30 subjects who initiated E/C/F/TDF. Twenty-nine subjects completed 48 weeks of follow-up. The majority were female (80%). There were no deaths, no new AIDS-associated clinical events, and one loss-to-follow-up. The median baseline CD4 count was 408 cells/mm3 (range: 34-747); which increased by a median +161 cells/mm3 (range: 27-547) at week 48. Twenty-five subjects had baseline HIV-2 VL of less than 50 copies/ml of plasma. In those with detectable HIV-2 VL, the median was 41 copies/ml (range: 10-6135). Using a mITT analysis (FDA Snapshot method), 28 of 30 (93.3%; 95% CI=77.9%-99.2%) had viral suppression at 48 weeks. The one subject with virologic failure had multidrug resistant HIV-2 (RT mutation: K65R; integrase mutations: G140S & Q148R) detected at week 48. There were eight grade 3-4 adverse events, none were deemed study related. Adherence and acceptability were good. Our data suggest that E/C/F/TDF, a once-daily, single-tablet-regimen, is safe, effective, and well-tolerated. Our findings support the use of integrase inhibitor-based regimens for HIV-2 treatment. NCT02180438.

Differential influence of vemurafenib and dabrafenib on patients’ lymphocytes despite similar clinical efficacy in melanoma

PubMed Central

Schilling, B.; Sondermann, W.; Zhao, F.; Griewank, K. G.; Livingstone, E.; Sucker, A.; Zelba, H.; Weide, B.; Trefzer, U.; Wilhelm, T.; Loquai, C.; Berking, C.; Hassel, J.; Kähler, K. C.; Utikal, J.; Al Ghazal, P.; Gutzmer, R.; Goldinger, S. M.; Zimmer, L.; Paschen, A.; Hillen, U.; Schadendorf, D.

2014-01-01

Background Since the majority of melanomas eventually become resistant and progress, combining selective BRAF inhibitors (BRAFi) with immunotherapies has been proposed to achieve more durable treatment responses. Here, we explored the impact of selective BRAFi on the hosts' immune system. Patients and methods Clinical data, whole blood counts (WBC) and serum lactate dehydrogenase (LDH) of 277 vemurafenib- and 65 dabrafenib-treated melanoma patients were evaluated. The frequency and phenotype of lymphocyte subpopulations were determined by flow cytometry while T cell cytokine secretion was measured by multiplex assays. Results Progression-free survival (PFS) as well as overall survival (OS) were similar in patients treated with either BRAFi. High pretreatment LDH was associated with shorter PFS and OS in both groups. During therapy, peripheral lymphocytes decreased by 24.3% (median, P < 0.0001) in vemurafenib-treated patients but remained unchanged in dabrafenib-treated patients (+1.2%, P = 0.717). Differentiation of peripheral lymphocytes of vemurafenib-treated patients showed a significant decrease in CD4+ T cells (P < 0.05). Within CD4+ T cells obtained during treatment, an increase in CCR7+CD45RA+ (naïve) and a decrease in CCR7+CD45RA− (central memory) populations were found (P < 0.01 for both). Furthermore, secretion of interferon-γ and interleukin-9 by CD4+ T cells was significantly lower in samples obtained during vemurafenib treatment compared with baseline samples. Conclusion While both compounds have comparable clinical efficacy, vemurafenib but not dabrafenib decreases patients peripheral lymphocyte counts and alters CD4+ T cell phenotype and function. Thus, selective BRAFi can significantly affect patients' peripheral lymphocyte populations. Fully understanding these effects could be critical for successfully implementing combinatorial therapies of BRAFi with immunomodulatory agents. PMID:24504444

Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers.

PubMed

Silva, Angela M Monteiro da; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves

2015-02-01

To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers.

Psychosocial factors and T lymphocyte counts in Brazilian peacekeepers

PubMed Central

Monteiro da Silva, Angela M; Speranza, Francisco A B; Ishii, Solange Kiyoko; Hirata, Raphael; Mattos-Guaraldi, Ana Luíza; Milagres, Lucimar Gonçalves

2015-01-01

OBJECTIVE: To investigate the associations between psychosocial factors and peripheral blood CD4 and CD8 T lymphocyte numbers in Brazilian peacekeepers. METHODS: Venous blood was collected from 759 peacekeepers who had just returned from a peace mission in Haiti. Among the 759 soldiers, 642 individuals completed the psychosocial measures. CD4 and CD8 T lymphocyte counts were measured by flow cytometry using a commercially available kit. Psychosocial factors, including military peace force stressors, clinical stress, anxiety and depression, were recorded. As a reference for T lymphocyte numbers, we measured T lymphocyte counts in 75 blood donors from the Instituto de Biologia do Exército, Rio de Janeiro. RESULTS: The median numbers of CD4 and CD8 T lymphocytes in the blood donors were 819 cells/µl and 496 cells/µl, respectively, with a CD4:CD8 ratio of 1.6. Significantly (p<0.05) lower CD4 T cell counts (759 cells/µl) were recorded for peacekeepers, with similar CD8 levels (548 cells/µl) and smaller CD4:CD8 ratios (1.3, p<0.001) compared to blood donors. These differences were due to a group of 14 military personnel with CD4 and CD8 medians of 308 and 266 cells/µl, respectively. Only one (7.1%) of these 14 individuals was diagnosed with clinical stress compared with 13.5% of the individuals with normal levels of CD4 T lymphocytes. One individual out of 628 (0.16%) had a Lipp's Stress Symptom Inventory score of 3, indicating near exhaustion. CONCLUSION: The prevalence of psychological disorders was low and there were no associations with CD4 or CD8 T cell numbers. PMID:25789525

Total lymphocyte count as a predictor of absolute CD4+ count and CD4+ percentage in HIV-infected persons.

PubMed

Blatt, S P; Lucey, C R; Butzin, C A; Hendrix, C W; Lucey, D R

1993-02-03

To determine whether the total lymphocyte count (TLC) accurately predicts a low absolute CD4+ T-cell count and CD4+ percentage in persons infected with human immunodeficiency virus (HIV). Retrospective analysis of data collected in the US Air Force HIV Natural History Study. Military medical center that performs annual medical evaluation of all HIV-infected US Air Force personnel. A total of 828 consecutive patients with no prior history of zidovudine use, evaluated from January 1985 through July 1991. For patients with multiple observations over time, a single data point within each 6-month interval was included in the analysis (N = 2866). The sensitivity, specificity, and likelihood ratio (LR) of the TLC, in the range of 1.00 x 10(9)/L to 2.00 x 10(9)/L, in predicting an absolute CD4+ T-cell count less than 0.20 x 10(9)/L or a CD4+ percentage less than 20% were calculated. In addition, the LR and pretest probability of significant immunosuppression were used to calculate posttest probabilities of a low CD4+ count for a given TLC value. The LR of the TLC in predicting an absolute CD4+ count < 0.20 x 10(9)/L increased from 2.4 (95% confidence interval, 2.2 to 2.5) for all TLCs less than 2.00 x 10(9)/L, to 33.2 (95% confidence interval, 24.1 to 45.7) for all TLCs less than 1.00 x 10(9)/L. The specificity for this prediction increased from 57% to 97% over this range. The LR also increased from 1.4 (95% confidence interval, 1.3 to 1.6) for all TLCs less than 2.00 x 10(9)/L to 9.7 (95% confidence interval, 7.1 to 13.1) for all TLCs less than 1.00 x 10(9)/L in predicting a CD4+ percentage less than 20%. The TLC, between 1.00 x 10(9)/L and 2.00 x 10(9)/L, appears to be a useful predictor of significant immunosuppression as measured by a CD4+ T-cell count less than 0.20 x 10(9)/L in HIV-infected persons. The LR for a given TLC value and the pretest probability of immunosuppression can be used to determine the posttest probability of significant immunosuppression in individual patients. For example, in a patient with a TLC less than 1.50 x 10(9)/L and a pretest probability of 16%, the posttest probability of a low CD4+ T-cell count increases to 53%. In contrast, a TLC greater than 2.00 x 10(9)/L in an individual with a pretest probability of 30% will decrease the posttest probability of a low CD4+ T-cell count to less than 4%. Physicians should find these data useful to help predict the risk for opportunistic infection among HIV-infected persons who present with syndromes that are potentially compatible with opportunistic infection but who have not had recent or prior CD4+ T-cell analysis.

The effect of energy-protein supplementation on weight, body composition and handgrip strength among pulmonary tuberculosis HIV-co-infected patients: randomised controlled trial in Mwanza, Tanzania.

PubMed

PrayGod, George; Range, Nyagosya; Faurholt-Jepsen, Daniel; Jeremiah, Kidola; Faurholt-Jepsen, Maria; Aabye, Martine G; Jensen, Lotte; Jensen, Andreas V; Grewal, Harleen M S; Magnussen, Pascal; Changalucha, John; Andersen, Aase Bengaard; Friis, Henrik

2012-01-01

Undernutrition is common among smear-positive pulmonary tuberculosis (PTB+) patients. Micronutrient supplementation may improve treatment outcomes, but it is unclear whether additional energy-protein would be beneficial. The present study aimed to assess the effect of energy-protein supplementation on weight, body composition and handgrip strength against a background of high micronutrient intake during tuberculosis (TB) treatment. A total of 377 PTB+ patients co-infected with HIV were randomly allocated one or six biscuits daily for 60 d during TB treatment. Weight, arm fat area, arm muscle area and handgrip strength were assessed at baseline and 2 and 5 months. There were no effects on any outcome at 2 months, but energy-protein supplementation was associated with a 1·3 (95 % CI - 0·1, 2·8) kg marginally significant gain in handgrip strength at 5 months. However, after 2 months, energy-protein supplementation led to a weight gain of 1·9 (95 % CI 0·1, 3·7) kg among patients with cluster of differentiation 4 (CD4) counts ≥ 350 cells/μl, but not among patients with low CD4 counts ( - 0·2 kg; 95 % CI - 1·3, 0·8, Pinteraction = 0·03). Similarly, at 5 months, energy-protein supplementation led to a 2·3 (95 % CI 0·6, 4·1) kg higher handgrip strength gain among patients with CD4 counts < 350 cells/μl, but not in those with high CD4 counts (Pinteraction = 0·04). In conclusion, energy-protein supplementation to PTB+ HIV-co-infected patients had no overall effects on weight and body composition, but was associated with marginally significant gain in handgrip strength. More research is needed to develop an effective supplement, before it is recommended to TB programmes.

PositiveLinks: A Mobile Health Intervention for Retention in HIV Care and Clinical Outcomes with 12-Month Follow-Up.

PubMed

Dillingham, Rebecca; Ingersoll, Karen; Flickinger, Tabor E; Waldman, Ava Lena; Grabowski, Marika; Laurence, Colleen; Wispelwey, Erin; Reynolds, George; Conaway, Mark; Cohn, Wendy F

2018-06-01

Mobile health interventions may help People Living with HIV (PLWH) improve engagement in care. We designed and piloted PositiveLinks, a clinic-affiliated mobile intervention for PLWH, and assessed longitudinal impact on retention in care and viral suppression. The program was based at an academic Ryan White Clinic serving a nonurban population in Central Virginia. The PL intervention included a smartphone app that connected participants to clinic staff and provided educational resources, daily queries of stress, mood and medication adherence, weekly quizzes, appointment reminders, and a virtual support group. Outcomes were analyzed using McNemar's tests for HRSA-1, visit constancy, and viral suppression and nonparametric Wilcoxon signed-rank tests for CD4 counts and viral loads. Of 77 participants, 63% were male, 49% black non-Hispanic, and 72% below the federal poverty level. Participants' achievement of a retention in care benchmark (HRSA-1) increased from 51% at baseline to 88% at 6 months (p < 0.0001) and 81% at 12 months (p = 0.0003). Visit constancy improved from baseline to 6 months (p = 0.016) and 12 months (p = 0.0004). Participants' mean CD4 counts increased from baseline to 6 months (p = 0.0007) and 12 months (p = 0.0005). The percentage of participants with suppressed viral loads increased from 47% at baseline to 87% at 6 months (p < 0.0001) and 79% at 12 months (p = 0.0007). This study is one of the first to demonstrate that a mobile health intervention can have a positive impact on retention in care and clinical outcomes for vulnerable PLWH. Next steps include integration with clinical practice and dissemination.

Dynamics of cellular HIV-1 DNA levels over 144 weeks of darunavir/ritonavir monotherapy versus triple therapy in the MONET trial.

PubMed

Geretti, Anna Maria; Arribas, Jose R; Lathouwers, Erkki; Foster, Geraldine M; Yakoob, Rabia; Kinloch, Sabine; Hill, Andrew; van Delft, Yvon; Moecklinghoff, Christiane

2013-01-01

In patients receiving combination antiretroviral therapy (ART), switching to monotherapy with ritonavir-boosted darunavir (DRV/r) can maintain plasma HIV-1 RNA suppression with no treatment-emergent drug resistance; effects on cellular HIV-1 DNA burden are less well characterized. In MONET, patients on stable combination ART for at least 6 months with plasma HIV-1 RNA <50 copies/mL and no history of virologic failure switched to DRV/r 800/100 mg once daily, either alone (n = 127) or with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (n = 129). In a representative subset of 146 patients, total HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) was tested retrospectively at baseline, week 48, week 96, and week 144. Mean HIV-1 DNA levels at baseline vs week 144 were 2.50 vs 2.49 log10 copies/106 PBMC in the monotherapy arm and 2.59 vs 2.61 log10 copies/106 PBMC in the triple therapy arm, with mean (median) changes of -0.05 (-0.03) and +0.03 (+0.01) log10 copies/106 PBMC in the 2 arms, respectively. Overall baseline HIV-1 DNA levels were higher in patients with nadir CD4 counts <200 cell/µL (P<.05) and in patients who over 144 weeks experienced at least 1 HIV-1 RNA measurement >50 copies/mL (P < .05). In this substudy of the MONET trial, HIV-1 DNA levels remained stable during 144 weeks of either DRV/r monotherapy or triple therapy with DRV/r + 2 NRTIs. In both treatment arms, baseline HIV-1 DNA levels were predicted by the nadir CD4 cell count and predictive of plasma HIV-1 RNA detection during follow-up.

PositiveLinks: A Mobile Health Intervention for Retention in HIV Care and Clinical Outcomes with 12-Month Follow-Up

PubMed Central

Ingersoll, Karen; Flickinger, Tabor E.; Waldman, Ava Lena; Grabowski, Marika; Laurence, Colleen; Wispelwey, Erin; Reynolds, George; Conaway, Mark; Cohn, Wendy F.

2018-01-01

Abstract Mobile health interventions may help People Living with HIV (PLWH) improve engagement in care. We designed and piloted PositiveLinks, a clinic-affiliated mobile intervention for PLWH, and assessed longitudinal impact on retention in care and viral suppression. The program was based at an academic Ryan White Clinic serving a nonurban population in Central Virginia. The PL intervention included a smartphone app that connected participants to clinic staff and provided educational resources, daily queries of stress, mood and medication adherence, weekly quizzes, appointment reminders, and a virtual support group. Outcomes were analyzed using McNemar's tests for HRSA-1, visit constancy, and viral suppression and nonparametric Wilcoxon signed-rank tests for CD4 counts and viral loads. Of 77 participants, 63% were male, 49% black non-Hispanic, and 72% below the federal poverty level. Participants' achievement of a retention in care benchmark (HRSA-1) increased from 51% at baseline to 88% at 6 months (p < 0.0001) and 81% at 12 months (p = 0.0003). Visit constancy improved from baseline to 6 months (p = 0.016) and 12 months (p = 0.0004). Participants' mean CD4 counts increased from baseline to 6 months (p = 0.0007) and 12 months (p = 0.0005). The percentage of participants with suppressed viral loads increased from 47% at baseline to 87% at 6 months (p < 0.0001) and 79% at 12 months (p = 0.0007). This study is one of the first to demonstrate that a mobile health intervention can have a positive impact on retention in care and clinical outcomes for vulnerable PLWH. Next steps include integration with clinical practice and dissemination. PMID:29851504

Prioritizing CD4 Count Monitoring in Response to ART in Resource-Constrained Settings: A Retrospective Application of Prediction-Based Classification

PubMed Central

Liu, Yan; Li, Xiaohong; Johnson, Margaret; Smith, Collette; Kamarulzaman, Adeeba bte; Montaner, Julio; Mounzer, Karam; Saag, Michael; Cahn, Pedro; Cesar, Carina; Krolewiecki, Alejandro; Sanne, Ian; Montaner, Luis J.

2012-01-01

Background Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation. Methods and Findings Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4+ T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4+ T cell count of 200 or 350 cells/µl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements <200 cells/µl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/µl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/µl. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold. Conclusions Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4+ T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. Please see later in the article for the Editors' Summary PMID:22529752

CMV retinitis recurs after stopping treatment in virological and immunological failures of potent antiretroviral therapy.

PubMed

Torriani, F J; Freeman, W R; Macdonald, J C; Karavellas, M P; Durand, D M; Jeffrey, D D; Meylan, P R; Schrier, R D

2000-01-28

To determine predictors of clinical relapse of cytomegalovirus (CMV) end-organ disease in a cohort of 17 HIV-infected patients with healed and treated CMV retinitis (CMVR) who responded to HAART with an increase in CD4 cell counts to above 70 cells/mm3 and discontinued CMV maintenance therapy (MT). Seventeen patients were monitored for reactivation of retinitis. The CD4 cell counts, HIV RNA and peripheral blood mononuclear cell (PBMC) lymphoproliferative assays to CMV at 3 month intervals were compared between patients with and without reactivation of CMVR. Positive lymphoproliferative responses were defined as a stimulation index of 3 or greater. Five out of 17 (29%) patients experienced a recurrence of CMVR a mean of 14.5 months after stopping CMV MT and between 8 days and 10 months after CD4 cell counts fell below 50 cells/mm3. Median CD4 cell counts and plasma HIV RNA at reactivation were 37 cells/mm3 and 5.3 log10 copies/ml. Three patients recurred at a previously active site of the retina, one had contralateral CMVR, and one a recurrence of retinitis and pancreatitis simultaneously. Mean lymphoproliferative responses to CMV were 2.4 in patients with reactivation versus 21.0 stimulation index (SI) in patients without reactivation (P= 0.01). A model incorporating four variables (CD4 cell counts and HIV RNA at maintenance discontinuation, highest CD4 cell count, nadir HIV RNA and median lymphoproliferative responses) identified correctly 88% of patients with and without reactivation. CMV disease recurs after virological and immunological failure of HAART if CD4 cell counts drop below 50. In this situation, anti-CMV agents should be resumed before clinical reactivation ensues, because of the risk of contralateral retinal involvement and systemic disease.

Cerebral signal intensity abnormalities on T2-weighted MR images in HIV patients with highly active antiretroviral therapy: relationship with clinical parameters and interval changes.

PubMed

Hanning, Uta; Husstedt, Ingo W; Niederstadt, Thomas-Ulrich; Evers, Stefan; Heindel, Walter; Kloska, Stephan P

2011-09-01

The aim of this study was to assess the relationship between immune state and cerebral signal intensity abnormalities (SIAs) on T2-weighted magnetic resonance images in subjects with human immunodeficiency virus type 1 infection and highly active antiretroviral therapy. Thirty-two subjects underwent a total of 109 magnetic resonance studies. The presence of human immunodeficiency virus-associated neurocognitive disorder, categorized CD4(+) T lymphocyte count, and plasma viral load were assessed for relationship with the severity and interval change of SIAs for different anatomic locations of the brain. Subjects with multifocal patterns of SIAs had CD4(+) cell counts < 200 cells/μL in 66.0%, whereas subjects with diffuse patterns of SIAs had CD4(+) cell counts < 200 cells/μL in only 31.4% (P < .001). Subjects without SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 37.0%, whereas subjects with minor and moderate SIAs in the basal ganglia had CD4(+) cell counts < 200 cells/μL in 78.3% and 80.0%, respectively (P < .005). The percentage of subjects with CD4(+) cell counts < 200 cells/μL was 85.7% when there were progressive periventricular SIA changes and 45.5% when periventricular SIA changes were stable in follow-up (P < .05). The presence and progression of cerebral SIAs on T2-weighted magnetic resonance images reflecting cerebral infection with human immunodeficiency virus are significantly related to impaired immune state as measured by CD4(+) cell count. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV.

PubMed

Triplette, Matthew; Attia, Engi F; Akgün, Kathleen M; Soo Hoo, Guy W; Freiberg, Matthew S; Butt, Adeel A; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T; Graber, Christopher J; Huang, Laurence; Crothers, Kristina

2017-01-01

The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1-39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era.

A Low Peripheral Blood CD4/CD8 Ratio Is Associated with Pulmonary Emphysema in HIV

PubMed Central

Attia, Engi F.; Akgün, Kathleen M.; Soo Hoo, Guy W.; Freiberg, Matthew S.; Butt, Adeel A.; Wongtrakool, Cherry; Goetz, Matthew Bidwell; Brown, Sheldon T.; Graber, Christopher J.; Huang, Laurence; Crothers, Kristina

2017-01-01

Objectives The prevalence of emphysema is higher among HIV-infected (HIV+) individuals compared to HIV-uninfected persons. While greater tobacco use contributes, HIV-related effects on immunity likely confer additional risk. Low peripheral blood CD4+ to CD8+ T-lymphocyte (CD4/CD8) ratio may reflect chronic inflammation in HIV and may be a marker of chronic lung disease in this population. Therefore, we sought to determine whether the CD4/CD8 ratio was associated with chronic obstructive pulmonary disease (COPD), particularly the emphysema subtype, in a cohort of HIV+ subjects. Methods We performed a cross-sectional analysis of 190 HIV+ subjects enrolled in the Examinations of HIV Associated Lung Emphysema (EXHALE) study. Subjects underwent baseline laboratory assessments, pulmonary function testing and chest computed tomography (CT) analyzed for emphysema severity and distribution. We determined the association between CD4/CD8 ratio and emphysema, and the association between CD4/CD8 ratio and pulmonary function markers of COPD. Results Mild or greater emphysema (>10% lung involvement) was present in 31% of subjects. Low CD4/CD8 ratio was associated with >10% emphysema in multivariable models, adjusting for risk factors including smoking, current and nadir CD4 count and HIV RNA level. Those with CD4/CD8 ratio <0.4 had 6.3 (1.1–39) times the odds of >10% emphysema compared to those with a ratio >1.0 in fully adjusted models. A low CD4/CD8 ratio was also associated with reduced diffusion capacity (DLCO). Conclusions A low CD4/CD8 ratio was associated with emphysema and low DLCO in HIV+ subjects, independent of other risk factors and clinical markers of HIV. The CD4/CD8 ratio may be a useful, clinically available, marker for risk of emphysema in HIV+ subjects in the antiretroviral therapy (ART) era. PMID:28122034

Prevalence of thrombocytopenia before and after initiation of HAART among HIV infected patients at black lion specialized hospital, Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Woldeamanuel, Gashaw Garedew; Wondimu, Diresibachew Haile

2018-01-01

Hematological abnormalities are common in HIV positive patients. Of these, thrombocytopenia is a known complication which has been associated with a variety of bleeding disorders. However, its magnitude and related factors have not been well-characterized in the era of highly active antiretroviral therapy (HAART) in Ethiopia. Therefore, this study aimed to assess the prevalence of thrombocytopenia before and after initiation of HAART among HIV positive patients attending Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A cross sectional study was conducted from February to April 2017 in Black Lion Specialized Hospital, Addis Ababa, Ethiopia. A total of 176 patients on HAART were selected using simple random sampling techniques. Socio-demographic and clinical characteristics of the study patients were collected using structured questionnaire. Measurements of platelet counts and CD4 + T cell counts were made using Sysmex XT 2000i hematology analyzer and BD FACS Count CD4 analyzer, respectively. Statistical analysis of the data (Paired T- test and binary logistic regression) was done using SPSS version 20. P -value < 0.05 was considered as statistically significant. A total of 176 patients (Age > 18 years old) were enrolled in this study and had a mean age of 40.08 ± 9.38 years. There was significant increase in the mean values of platelet counts (218.44 ± 106.6 × 10 3 /μl vs 273.65 ± 83.8 × 10 3 /μl, p  < 0.001) after six months of HAART initiation compared to the baseline. Prevalence of thrombocytopenia before and after HAART initiation was 25 and 5.7% respectively. HIV patients whose CD4 counts < 200 Cells/μl were more likely to have thrombocytopenia than HIV patients whose CD4 count ≥350 Cells/μl. However, it was not statistically associated with prevalence of thrombocytopenia. This study has shown that the prevalence of thrombocytopenia after HAART initiation was decreased significantly. Based on our results, a number of study participants still had thrombocytopenia after initiation of HAART. Therefore, continuous screening for thrombocytopenia among HIV infected patients should be performed to decrease the risk of morbidity and mortality.

Perfect count: a novel approach for the single platform enumeration of absolute CD4+ T-lymphocytes.

PubMed

Storie, Ian; Sawle, Alex; Goodfellow, Karen; Whitby, Liam; Granger, Vivian; Ward, Rosalie Y; Peel, Janet; Smart, Theresa; Reilly, John T; Barnett, David

2004-01-01

The derivation of reliable CD4(+) T lymphocyte counts is vital for the monitoring of disease progression and therapeutic effectiveness in HIV(+) individuals. Flow cytometry has emerged as the method of choice for CD4(+) T lymphocyte enumeration, with single-platform technology, coupled with reference counting beads, fast becoming the "gold standard." However, although single-platform, bead-based, sample acquisition requires the ratio of beads to cells to remain unchanged, there is no available method, until recently, to monitor this. Perfect Count beads have been developed to address this issue and to incorporate two bead populations, with different densities, to allow the detection of inadequate mixing. Comparison of the relative proportions of both beads with the manufacture's defined limits enables an internal QC check during sample acquisition. In this study, we have compared CD4(+) T lymphocyte counts, obtained from 104 HIV(+) patients, using TruCount beads with MultiSet software (defined as the predicated method) and the new Perfect Count beads, incorporating an in house sequential gating strategy. We have demonstrated an excellent degree of correlation between the predicate method and the Perfect Count system (r(2) = 0.9955; Bland Altman bias +27 CD4(+) T lymphocytes/microl). The Perfect Count system is a robust method for performing single platform absolute counts and has the added advantage of having internal QC checks. Such an approach enables the operator to identify potential problems during sample preparation, acquisition and analysis. Copyright 2003 Wiley-Liss, Inc.

Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy

PubMed Central

Castaneda, Carlos A; Mittendorf, Elizabeth; Casavilca, Sandro; Wu, Yun; Castillo, Miluska; Arboleda, Patricia; Nunez, Teresa; Guerra, Henry; Barrionuevo, Carlos; Dolores-Cerna, Ketty; Belmar-Lopez, Carolina; Abugattas, Julio; Calderon, Gabriela; De La Cruz, Miguel; Cotrina, Manuel; Dunstan, Jorge; Gomez, Henry L; Vidaurre, Tatiana

2016-01-01

AIM To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response (pCR) (P = 0.0251) and outcome (P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections (ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. Post-NAC lesions with pCR had similar TIL levels than those without pCR (P = 0.6331). NAC produced a TIL decrease in full-face sections (P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival (DFS). Higher counts of CD3 in pre-NAC samples had longer overall-survival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR. CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related. PMID:27777881

The effects of age on associations between markers of HIV progression and markers of metabolic function including albumin, haemoglobin and lipid concentrations.

PubMed

Samuel, M; Jose, S; Winston, A; Nelson, M; Johnson, M; Chadwick, D; Fisher, M; Leen, C; Gompels, M; Gilson, R; Post, F A; Hay, P; Sabin, C A

2014-05-01

We investigated whether age modified associations between markers of HIV progression, CD4 T lymphocyte count and HIV RNA viral load (VL), and the following markers of metabolic function: albumin, haemoglobin, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). A retrospective analysis of data from the United Kingdom Collaborative HIV Cohort was carried out. Analyses were limited to antiretroviral-naïve subjects to focus on the impact of HIV disease itself. A total of 16670 subjects were included in the analysis. Multilevel linear regression models assessed associations between CD4 count/VL and each of the outcomes. Statistical tests for interactions assessed whether associations differed among age groups. After adjustment for gender and ethnicity, there was evidence that lower CD4 count and higher VL were associated with lower TC, LDL-C, haemoglobin and albumin concentrations but higher triglyceride concentrations. Age modified associations between CD4 count and albumin (P < 0.001) and haemoglobin (P = 0.001), but not between CD4 count and HDL-C, LDL-C and TC, or VL and any outcome. Among participants aged < 30, 30-50 and > 50 years, a 50 cells/μL lower CD4 count correlated with a 2.4 [95% confidence interval (CI) 1.7-3.0], 3.6 (95% CI 3.2-4.0) and 5.1 (95% CI 4.0-6.1) g/L lower haemoglobin concentration and a 0.09 (95% CI 0.07-0.11), 0.12 (95% CI 0.11-0.13) and 0.16 (95% CI 0.13-0.19) g/L lower albumin concentration, respectively. We present evidence that age modifies associations between CD4 count and plasma albumin and haemoglobin levels. A given reduction in CD4 count was associated with a greater reduction in haemoglobin and albumin concentrations among older people living with HIV. These findings increase our understanding of how the metabolic impact of HIV is influenced by age. © 2013 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

Effects of iridoid-anthocyanin extract of Cornus mas L. on hematological parameters, population and proliferation of lymphocytes during experimental infection of mice with Trichinella spiralis.

PubMed

Piekarska, Jolanta; Szczypka, Marianna; Kucharska, Alicja Z; Gorczykowski, Michał

2018-05-01

The influence of iridoid-anthocyanin aqueous extract of cornelian cherry fruits (CM) on hematological parameters, lymphocyte subsets and proliferation during Trichinella spiralis infection in mice was investigated. CM (100 mg/kg) was administered orally to T. spiralis-infected mice six times within a period encompassing three days prior to the infection and three days after the infection (dai). CM increased the percentage of CD3 + , CD4 + cells and CD4 + /CD8 + ratio and decreased total count of CD8 + and CD19 + splenocytes (5 th dai). An increase in total count of CD4 + , CD3 + , CD19 + splenocytes was observed (21 st dai). CM elevated the percentage of CD4 + cells (7 th dai) and CD4 + /CD8 + ratio (21 st dai) in MLN. CM increased (14 th dai) and then reduced (21 st dai) the percentage of CD8 + MLN lymphocytes and decreased total count of MLN CD8 + cells (21 st dai) and B cells (14 th dai). An activation of lymphocyte proliferation in spleen and simultaneous decrease in MLN on 5 th dai was observed. An increase in red blood cells parameters (5 th dai) and in leukocyte count (7 th dai) was found. A rise in platelet count was noticed both on 5 th and 7 th dai. Moreover, the number of adult T. spiralis on 5 th dai in mice receiving CM extract was lower than in the control mice. These results suggested that iridoid-anthocyanin aqueous extract of CM stimulated murine immune response during T. spiralis infection. Copyright © 2018 Elsevier Inc. All rights reserved.

Aerobic exercise: effects on parameters related to fatigue, dyspnea, weight and body composition in HIV-infected adults.

PubMed

Smith, B A; Neidig, J L; Nickel, J T; Mitchell, G L; Para, M F; Fass, R J

2001-04-13

The purpose of the study was to examine the effects of aerobic exercise on physiological fatigue (time on treadmill), dyspnea [rate of perceived exertion (RPE) and forced expiratory volume at 1 s (FEV1)], weight, and body composition in HIV-1-infected adults (200-499 x 106 CD4+ cells/l). The study was a randomized, wait-listed, controlled clinical trial of aerobic exercise in HIV-1-infected adults on signs and symptoms associated with HIV-1 infection or its treatment. Sixty subjects were recruited and randomized to two groups. Experimental subjects completed a 12-week supervised exercise program. Control subjects continued usual activity from baseline to week 12 and were then were enrolled in the exercise program. At baseline, the groups were similar in age, weight, body mass index [mean body mass index (BMI) > 27], time since diagnosis, number of symptoms, CD4+ cell count, and number on protease inhibitor therapy (n = 7). Despite disproportionate attrition from the exercise group (38%), exercise subjects were able to remain on the treadmill longer, lost weight, decreased BMI, subcutaneous fat, and abdominal girth when compared to controls. The improvement in weight and body composition occurred without a decrease in kilocalories consumed. Exercise did not seem to have an effect on RPE, a surrogate for dyspnea, and FEV1. There was no significant difference in either the change in CD4+ cell count, percentage or copies of plasma HIV-1 RNA between groups. We conclude that supervised aerobic exercise training safely decreases fatigue, weight, BMI, subcutaneous fat and abdominal girth (central fat) in HIV-1-infected individuals. It did not appear to have an effect on dyspnea.

Survival of people on antiretroviral treatment in Zambia: a retrospective cohort analysis of HIV clients on ART.

PubMed

Amanzi, Patrick; Michelo, Charles; Simoonga, Christopher; Dambe, Rosalia; Chongwe, Gershom

2016-01-01

Provision of free anti-retroviral therapy in Zambia started in June 2004. There were only 15,000 people on treatment as at December that year, mainly due to lack of access. This number rose to 580,000 people as at December 2013. The general objective of this study was to determine survival of people on ART and to examine associated predictors for survival. The study included ART patients enrolled between the year 2002 and 2013 (n=10,395) in 285 health facilities in Zambia. Patient files were analyzed retrospectively. The study used Kaplan Meier and Cox-proportional hazard models to describe the relationship between lost to follow up and age, sex, baseline CD4 cell count and weight. Results showed that lost to follow up accounted for 90% of the clients that had dropped out, while 10% was to deaths. Low baseline CD4 count (p-value 0.001, HR 0.9994, (95% CI 0.9993, 0.9996) at initiation was associated with lost to follow up together with weight at initiation (p-value 0.031, HR 0.9987 at 95% CI (0.9975, 0.9998)) of ART. This study has demonstrated that lost to follow up is a substantial contributing factor to drop outs among HIV patients on treatment. Strengthening of community treatment supporters especially immediate family members in emphasizing to the client the need to continue treatment is necessary. The health facility could do more in emphasizing the importance of treatment especially in the initial stages. Further, in order to reduce opportunistic infections and probable deaths during treatment, cotrimoxazole prophylaxis should be maintained so as to raise the CD4 levels. Improved nutritional assessment and counseling to boost the nutritional status of the clients throughout should be encouraged.

Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial.

PubMed

Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E; Wallis, Carol L; Tripathy, Srikanth; Morgado, Mariza G; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G; Lama, Javier R; Rassool, Mohammed; Santos, Breno R; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B; Eshleman, Susan H

2015-05-15

Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22-.98). In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. NCT00084136. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy

PubMed Central

Dalod, Marc; Dupuis, Marion; Deschemin, Jean-Christophe; Sicard, Didier; Salmon, Dominique; Delfraissy, Jean-Francois; Venet, Alain; Sinet, Martine; Guillet, Jean-Gerard

1999-01-01

The ex vivo antiviral CD8+ repertoires of 34 human immunodeficiency virus (HIV)-seropositive patients with various CD4+ T-cell counts and virus loads were analyzed by gamma interferon enzyme-linked immunospot assay, using peptides derived from HIV type 1 and Epstein-Barr virus (EBV). Most patients recognized many HIV peptides, with markedly high frequencies, in association with all the HLA class I molecules tested. We found no correlation between the intensity of anti-HIV CD8+ responses and the CD4+ counts or virus load. In contrast, the polyclonality of anti-HIV CD8+ responses was positively correlated with the CD4+ counts. The anti-EBV responses were significantly less intense than the anti-HIV responses and were positively correlated with the CD4+ counts. Longitudinal follow-up of several patients revealed the remarkable stability of the anti-HIV and anti-EBV CD8+ responses in two patients with stable CD4+ counts, while both antiviral responses decreased in two patients with obvious progression toward disease. Last, highly active antiretroviral therapy induced marked decreases in the number of anti-HIV CD8+ T cells, while the anti-EBV responses increased. These findings emphasize the magnitude of the ex vivo HIV-specific CD8+ responses at all stages of HIV infection and suggest that the CD8+ hyperlymphocytosis commonly observed in HIV infection is driven mainly by virus replication, through intense, continuous activation of HIV-specific CD8+ T cells until ultimate progression toward disease. Nevertheless, highly polyclonal anti-HIV CD8+ responses may be associated with a better clinical status. Our data also suggest that a decrease of anti-EBV CD8+ responses may occur with depletion of CD4+ T cells, but this could be restored by highly active antiretroviral treatment. PMID:10438796

Universal test and treat is not associated with sub-optimal antiretroviral therapy adherence in rural South Africa: the ANRS 12249 TasP trial.

PubMed

Iwuji, Collins; McGrath, Nuala; Calmy, Alexandra; Dabis, Francois; Pillay, Deenan; Newell, Marie-Louise; Baisley, Kathy; Porter, Kholoud

2018-06-01

HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub-optimal adherence (<95%) during the first 12 months of ART. A prospective cohort study nested within a two-arm cluster-randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu-Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six-monthly thereafter. We pooled data from participants in both arms and used random-effects logistic regression models to examine the association between CD4 count at ART initiation and sub-optimal adherence, and assessed if adherence levels were associated with virological suppression. Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm 3 (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub-optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub-optimal adherence with every 100 cells/mm 3 increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC). We found no evidence that higher CD4 counts at ART initiation were associated with sub-optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long-term outcomes are needed. ClinicalTrials.gov NCT01509508. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Fluorescein dye improves microscopic evaluation and counting of demodex in blepharitis with cylindrical dandruff.

PubMed

Kheirkhah, Ahmad; Blanco, Gabriela; Casas, Victoria; Tseng, Scheffer C G

2007-07-01

To show whether fluorescein dye helps detect and count Demodex embedded in cylindrical dandruff (CD) of epilated eyelashes from patients with blepharitis. Two eyelashes with CD were removed from each lid of 10 consecutive patients with blepharitis and subjected to microscopic examination with and without fluorescein solution to detect and count Demodex mites. Of 80 eyelashes examined, 36 (45%) lashes retained their CD after removal. Before addition of the fluorescein solution, the mean total Demodex count per patient was 14.9 +/- 10 and the mean Demodex count per lash was 3.1 +/- 2.5 and 0.8 +/- 0.7 in epilated eyelashes with and without retained CD, respectively (P < 0.0001). After addition of the fluorescein solution, opaque and compact CD instantly expanded to reveal embedded mites in a yellowish and semitransparent background. As a result, the mean total Demodex count per patient was significantly increased to 20.2 +/- 13.8 (P = 0.003), and the mean count per lash was significantly increased to 4.4 +/- 2.8 and 1 +/- 0.8 in eyelashes with and without retained CD (P < 0.0001 and P = 0.007), respectively. This new method yielded more mites in 8 of 10 patients and allowed mites to be detected in 3 lashes with retained CD and 1 lash without retained CD that had an initial count of zero. Addition of fluorescein solution after mounting further increases the proficiency of detecting and counting mites embedded in CD of epilated eyelashes.

Risk factors for treatment-limiting toxicities in patients starting nevirapine-containing antiretroviral therapy.

PubMed

Kesselring, Anouk M; Wit, Ferdinand W; Sabin, Caroline A; Lundgren, Jens D; Gill, M John; Gatell, Jose M; Rauch, Andri; Montaner, Julio S; de Wolf, Frank; Reiss, Peter; Mocroft, Amanda

2009-08-24

This collaboration of seven observational clinical cohorts investigated risk factors for treatment-limiting toxicities in both antiretroviral-naive and experienced patients starting nevirapine-based combination antiretroviral therapy (NVPc). Patients starting NVPc after 1 January 1998 were included. CD4 cell count at starting NVPc was classified as high (>400/microl/>250/microl for men/women, respectively) or low. Cox models were used to investigate risk factors for discontinuations due to hypersensitivity reactions (HSR, n = 6547) and discontinuation of NVPc due to treatment-limiting toxicities and/or patient/physician choice (TOXPC, n = 10,186). Patients were classified according to prior antiretroviral treatment experience and CD4 cell count/viral load at start NVPc. Models were stratified by cohort and adjusted for age, sex, nadir CD4 cell count, calendar year of starting NVPc and mode of transmission. Median time from starting NVPc to TOXPC and HSR were 162 days [interquartile range (IQR) 31-737] and 30 days (IQR 17-60), respectively. In adjusted Cox analyses, compared to naive patients with a low CD4 cell count, treatment-experienced patients with high CD4 cell count and viral load more than 400 had a significantly increased risk for HSR [hazard ratio 1.45, confidence interval (CI) 1.03-2.03] and TOXPC within 18 weeks (hazard ratio 1.34, CI 1.08-1.67). In contrast, treatment-experienced patients with high CD4 cell count and viral load less than 400 had no increased risk for HSR 1.10 (0.82-1.46) or TOXPC within 18 weeks (hazard ratio 0.94, CI 0.78-1.13). Our results suggest it may be relatively well tolerated to initiate NVPc in antiretroviral-experienced patients with high CD4 cell counts provided there is no detectable viremia.

Relationship of long-term highly active antiretroviral therapy on salivary flow rate and CD4 Count among HIV-infected patients.

PubMed

Kumar, J Vijay; Baghirath, P Venkat; Naishadham, P Parameswar; Suneetha, Sujai; Suneetha, Lavanya; Sreedevi, P

2015-01-01

To determine if long-term highly active antiretroviral therapy (HAART) therapy alters salivary flow rate and also to compare its relation of CD4 count with unstimulated and stimulated whole saliva. A cross-sectional study was performed on 150 individuals divided into three groups. Group I (50 human immunodeficiency virus (HIV) seropositive patients, but not on HAART therapy), Group II (50 HIV-infected subjects and on HAART for less than 3 years called short-term HAART), Group III (50 HIV-infected subjects and on HAART for more than or equal to 3 years called long-term HAART). Spitting method proposed by Navazesh and Kumar was used for the measurement of unstimulated and stimulated salivary flow rate. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. The mean CD4 count was 424.78 ± 187.03, 497.82 ± 206.11 and 537.6 ± 264.00 in the respective groups. Majority of the patients in all the groups had a CD4 count between 401 and 600. Both unstimulated and stimulated whole salivary (UWS and SWS) flow rates in Group I was found to be significantly higher than in Group II (P < 0.05). Unstimulated salivary flow rate between Group II and III subjects were also found to be statistically significant (P < 0.05). ANOVA performed between CD4 count and unstimulated and stimulated whole saliva in each group demonstrated a statistically significant relationship in Group II (P < 0.05). There were no significant results found between CD4 count and stimulated whole saliva in each groups. The reduction in CD4 cell counts were significantly associated with salivary flow rates of HIV-infected individuals who are on long-term HAART.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hughes, Michael A.; Parisi, Michele; Grossman, Stuart

Purpose: Patients with primary brain tumors are often treated with high doses of corticosteroids for prolonged periods to reduce intracranial swelling and alleviate symptoms such as headaches. This treatment may lead to immunosuppression, placing the patient at risk of life-threatening opportunistic infections, such as Pneumocystis carinii pneumonia. The risk of contracting some types of infection may be reduced with prophylactic antibiotics. The purpose of this study was to determine the occurrence of low CD4 counts and whether monitoring CD4 counts during and after radiotherapy (RT) is warranted. Methods and Materials: CD4 counts were measured during RT in 70 of 76more » consecutive patients with newly diagnosed Grade III and IV astrocytoma and anaplastic oligodendroglioma treated with corticosteroids and seen at the Johns Hopkins Hospital. Weekly CD4 measurements were taken in the most recent 25 patients. Prophylactic trimethoprim-sulfamethoxazole (160 mg/800 mg p.o. every Monday, Wednesday, and Friday) or dapsone (100 mg p.o. daily) in those with sulfa allergy was prescribed only if patients developed a low CD4 count. Carmustine chemotherapy wafers were placed at surgery in 23% of patients, evenly distributed between the groups. No patient received any other chemotherapy concurrent with RT. Results: CD4 counts decreased to <200/mm{sup 3} in 17 (24%) of 70 patients. For the 25 patients with weekly CD4 counts, all CD4 counts were >450/mm{sup 3} before RT, but 6 (24%) of 25 fell to <200/mm{sup 3} during RT. Patients with counts <200/mm{sup 3} were significantly more likely to be hospitalized (41% vs. 9%, p <0.01) and be hospitalized for infection (23% vs. 4%, p <0.05) during RT. Overall survival was not significantly different between the groups. All patients with low CD4 counts were treated with prophylactic antibiotics, and no patient developed Pneumocystis carinii pneumonia. No patients developed a serious adverse reaction to antibiotic therapy. The mean dose of steroids, mean minimal white blood cell count, and number of patients treated with Gliadel wafers were not significantly different between the groups. Conclusion: The results of this study have confirmed the clinical impression that the use of high-dose corticosteroids and RT in patients with primary brain cancer is sufficient to result in severe immunosuppression and place these patients at risk of life-threatening opportunistic infections. A protocol of prophylactic antibiotics for those at risk may help prevent a potentially fatal side effect of treatment. A prospective study is underway to determine the frequency, depth, and prognostic implications of this finding.« less

The Protective Role of the Family and Social Support Network in a Sample of HIV-Positive African American Women: Results of a Pilot Study

PubMed Central

Robbins, Michael; Szapocznik, José; Tejeda, Manuel; Samuels, Deanne; Ironson, Gail; Antoni, Michael

2005-01-01

This study examined the role of family functioning and social support in protecting HIV-positive African American women from the adverse psychological consequences associated with deterioration in their CD4 cell count. Participants were 38 African American HIV-positive women who had recently given birth. Results demonstrated that changes in CD4 cell counts were inversely predictive of psychological distress and were moderated by family functioning and social support satisfaction. Women with good family functioning were less affected by changes in their CD4 cell counts, and women with poor family functioning were more emotionally responsive to changes in CD4 cell count. Unexpectedly, women from families where conflicts tended to be clearly laid out and discussed were also more responsive to both changes in CD4 cell counts. Interventions are recommended that increase a client’s social support satisfaction, foster an adaptive level of connectedness to family, and enhance the family’s range of conflict resolution styles. PMID:16609750

Short-Term Clinical Disease Progression in HIV-Infected Patients Receiving Combination Antiretroviral Therapy: Results from the TREAT Asia HIV Observational Database

PubMed Central

Srasuebkul, Preeyaporn; Lim, Poh Lian; Lee, Man Po; Kumarasamy, Nagalingeswaran; Zhou, Jialun; Sirisanthana, Thira; Li, Patrick C. K.; Kamarulzaman, Adeeba; Oka, Shinichi; Phanuphak, Praphan; Vonthanak, Saphonn; Merati, Tuti P.; Chen, Yi-Ming A.; Sungkanuparph, Somnuek; Tau, Goa; Zhang, Fujie; Lee, Christopher K. C.; Ditangco, Rossana; Pujari, Sanjay; Choi, Jun Y.; Smith, Jeffery; Law, Matthew G.

2009-01-01

Objective The aim of our study was to develop, on the basis of simple clinical data, predictive short-term risk equations for AIDS or death in Asian patients infected with human immunodeficiency virus (HIV) who were included in the TREAT Asia HIV Observational Database. Methods Inclusion criteria were highly active antiretroviral therapy initiation and completion of required laboratory tests. Predictors of short-term AIDS or death were assessed using Poisson regression. Three different models were developed: a clinical model, a CD4 cell count model, and a CD4 cell count and HIV RNA level model. We separated patients into low-risk, high-risk, and very high-risk groups according to the key risk factors Identified. Results In the clinical model, patients with severe anemia or a body mass index (BMI; calculated as the weight in kilograms divided by the square of the height in meters) ≤18 were at very high risk, and patients who were aged <40 years or were male and had mild anemia were at high risk. In the CD4 cell count model, patients with a CD4 cell count <50 cells/µL, severe anemia, or a BMI ≤18 were at very high risk, and patients who had a CD4 cell count of 51–200 cells/µL, were aged <40 years, or were male and had mild anemia were at high risk. In the CD4 cell count and HIV RNA level model, patients with a CD4 cell count <50 cells/µL, a detectable viral load, severe anemia, or a BMI ≤18 were at very high risk, and patients with a CD4 cell count of 51–200 cells/µL and mild anemia were at high risk. The incidence of new AIDS or death in the clinical model was 1.3, 4.9, and 15.6 events per 100 person-years in the low-risk, high-risk, and very high-risk groups, respectively. In the CD4 cell count model the respective incidences were 0.9, 2.7, and 16.02 events per 100 person-years; in the CD4 cell count and HIV RNA level model, the respective incidences were 0.8, 1.8, and 6.2 events per 100 person-years. Conclusions These models are simple enough for widespread use in busy clinics and should allow clinicians to identify patients who are at high risk of AIDS or death in Asia and the Pacific region and in resource-poor settings. PMID:19226231

Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002.

PubMed

Dorrucci, Maria; Rezza, Giovanni; Porter, Kholoud; Phillips, Andrew

2007-02-15

To determine whether early postseroconversion CD4 cell counts and human immunodeficiency virus (HIV) loads have changed over time. Our analysis was based on 22 cohorts of people with known dates of seroconversion from Europe, Australia, and Canada (Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration). We focused on individuals seroconverting between 1985 and 2002 who had the first CD4 cell count (n=3687) or HIV load (n=1584) measured within 2 years of seroconversion and before antiretroviral use. Linear regression models were used to assess time trends in postseroconversion CD4 cell count and HIV load. Trends in time to key thresholds were also assessed, using survival analysis. The overall median initial CD4 cell count was 570 cells/ microL (interquartile range [IQR], 413-780 cells/ microL). The median initial HIV load was 35,542 copies/mL (IQR, 7600-153,050 copies/mL; on log(10) scale, 3.9-5.2 log(10) copies/mL). The postseroconversion CD4 cell count changed by an average of -6.33 cells/ microL/year (95% confidence interval [CI], -8.47 to -4.20 cells/ microL/year; P<.001), whereas an increase was observed in log(10) HIV load (+0.044 log(10) copies/mL/year; 95% CI, +0.034 to +0.053 log(10) copies/mL/year). These trends remained after adjusting for potential confounders. The probability of progressing to a CD4 cell count of <500 cells/ microL by 24 months from seroconversion increased from 0.66 (95% CI, 0.63-0.69) for individuals who seroconverted before 1991 to 0.80 (95% CI, 0.75-0.84) for those who seroconverted during 1999-2002. These data suggest that, in Europe, there has been a trend of decrease in the early CD4 cell count and of increase in the early HIV load. Additional research will be necessary to determine whether similar trends exist in other geographical areas.

Cardiovascular risk factors associated with lower baseline cognitive performance in HIV-positive persons.

PubMed

Wright, E J; Grund, B; Robertson, K; Brew, B J; Roediger, M; Bain, M P; Drummond, F; Vjecha, M J; Hoy, J; Miller, C; Penalva de Oliveira, A C; Pumpradit, W; Shlay, J C; El-Sadr, W; Price, R W

2010-09-07

To determine factors associated with baseline neurocognitive performance in HIV-infected participants enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) neurology substudy. Participants from Australia, North America, Brazil, and Thailand were administered a 5-test neurocognitive battery. Z scores and the neurocognitive performance outcome measure, the quantitative neurocognitive performance z score (QNPZ-5), were calculated using US norms. Neurocognitive impairment was defined as z scores <-2 in two or more cognitive domains. Associations of test scores, the QNPZ-5, and impairment with baseline factors including demographics and risk factors for HIV-associated dementia (HAD) and cardiovascular disease (CVD) were determined in multiple regression. The 292 participants had a median CD4 cell count of 536 cells/mm(3), 88% had an HIV viral load < or =400 copies/mL, and 92% were taking antiretrovirals. Demographics, HIV, and clinical factors differed between locations. The mean QNPZ-5 score was -0.72; 14% of participants had neurocognitive impairment. For most tests, scores and z scores differed significantly between locations, with and without adjustment for age, sex, education, and race. Prior CVD was associated with neurocognitive impairment. Prior CVD, hypercholesterolemia, and hypertension were associated with poorer neurocognitive performance but conventional HAD risk factors and the CNS penetration effectiveness rank of antiretroviral regimens were not. In this HIV-positive population with high CD4 cell counts, neurocognitive impairment was associated with prior CVD. Lower neurocognitive performance was associated with prior CVD, hypertension, and hypercholesterolemia, but not conventional HAD risk factors. The contribution of CVD and cardiovascular risk factors to the neurocognition of HIV-positive populations warrants further investigation.

Viral dynamics and CD4+ T cell counts in subtype C human immunodeficiency virus type 1-infected individuals from southern Africa.

PubMed

Gray, Clive M; Williamson, Carolyn; Bredell, Helba; Puren, Adrian; Xia, Xiaohua; Filter, Ruben; Zijenah, Lynn; Cao, Huyen; Morris, Lynn; Vardas, Efthyia; Colvin, Mark; Gray, Glenda; McIntyre, James; Musonda, Rosemary; Allen, Susan; Katzenstein, David; Mbizo, Mike; Kumwenda, Newton; Taha, Taha; Karim, Salim Abdool; Flores, Jorge; Sheppard, Haynes W

2005-04-01

Defining viral dynamics in natural infection is prognostic of disease progression and could prove to be important for vaccine trial design as viremia may be a likely secondary end point in phase III HIV efficacy trials. There are limited data available on the early course of plasma viral load in subtype C HIV-1 infection in Africa. Plasma viral load and CD4+ T cell counts were monitored in 51 recently infected subjects for 9 months. Individuals were recruited from four southern African countries: Zambia, Malawi, Zimbabwe, and South Africa and the median estimated time from seroconversion was 8.9 months (interquartile range, 5.7-14 months). All were infected with subtype C HIV-1 and median viral loads, measured using branched DNA, ranged from 3.82-4.02 log10 RNA copies/ml from 2-24 months after seroconversion. Viral loads significantly correlated with CD4+ cell counts (r=-0.5, p<0.0001; range, 376-364 cells/mm3) and mathematical modeling defined a median set point of 4.08 log10 (12 143 RNA copies/ml), which was attained approximately 17 months after seroconversion. Comparative measurements using three different viral load platforms (bDNA, Amplicor, and NucliSens) confirmed that viremia in subtype C HIV-1-infected individuals within the first 2 years of infection did not significantly differ from that found in early subtype B infection. In conclusion, the course of plasma viremia, as described in this study, will allow a useful baseline comparator for understanding disease progression in an African setting and may be useful in the design of HIV-1 vaccine trials in southern Africa.

Circulating lymphocyte levels and relationship with infection status in patients with relapsing-remitting multiple sclerosis treated with daclizumab beta.

PubMed

Giovannoni, Gavin; Wiendl, Heinz; Turner, Benjamin; Umans, Kimberly; Mokliatchouk, Oksana; Castro-Borrero, Wanda; Greenberg, Steven J; McCroskery, Peter; Giannattasio, Giorgio

2017-09-01

Reversible lymphocyte count reductions have occurred following daclizumab beta treatment for relapsing-remitting multiple sclerosis. To analyse total and differential lymphocyte levels and relationship with infection status. In DECIDE, blood samples were collected at 12-week intervals from daclizumab beta- ( n = 919) or intramuscular interferon beta-1a-treated ( n = 922) patients. Infections/serious infections were assessed proximate to grade 2/3 lymphopenia or low CD4 + /CD8 + T-cell counts. Total safety population (TSP) data were additionally analysed from the entire clinical development programme ( n = 2236). Over 96 weeks in DECIDE, mean absolute lymphocyte count (ALC), CD4 + and CD8 + T-cell counts decreased <10% (7.1% vs 1.6%, 9.7% vs 2.0%, 9.3% vs 5.9%: daclizumab beta vs interferon beta-1a, respectively); shifts to ALC below lower limit of normal occurred in 13% versus 15%, respectively. Grade 3 lymphopenia was uncommon (TSP: <1%) and transient. Lymphocyte changes generally occurred within 24 weeks after treatment initiation and were reversible within 12 weeks of discontinuation. In DECIDE, mean CD4 + /CD8 + T-cell counts were similar regardless of infection status. TSP data were consistent with DECIDE. When observed, ALC and CD4 + /CD8 + T-cell count decreases in daclizumab beta-treated patients were generally mild-to-modest, reversible upon treatment discontinuation and not associated with increased risk of infections, including opportunistic infections.

Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals.

PubMed

Kelly, Deborah; Burt, Kimberley; Missaghi, Bayan; Barrett, Lisa; Keynan, Yoav; Fowke, Keith; Grant, Michael

2012-08-31

Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. Assess vaccine-related effects on CD4(+) T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. A single dose of Arepanrix™ split vaccine including 3.75 μg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1-5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4(+) T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4(+) T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4(+) T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4(+) T cell numbers, which was greater amongst responders. We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals without pre-existing antibodies against H1N1 HA and a minor transient fall in CD4(+) T cell numbers, which was accentuated in responders. A single injection of the Arepanrix™ pandemic A/California/07/2009 H1N1 HA split vaccine may be insufficient to induce protective immunity in HIV-infected individuals without pre-existing anti-H1N1 HA responses.

Predictors of Loss to Follow-up Among HIV-infected Patients in a Rural South-Eastern Nigeria Hospital: A 5-year Retrospective Cohort Study

PubMed Central

Eguzo, KN; Lawal, AK; Umezurike, CC; Eseigbe, CE

2015-01-01

Background: Patient attrition has been a challenge in managing HIV programs in resource-limited settings. Aim: This study reviews the predictors of loss to follow-up (LTFU) in our hospital and suggests the best practices for dealing with the issue. Subjects and Methods: A 5-year retrospective cohort study of 1256 HIV-infected patients. Baseline CD4 counts, age, gender, year of enrolment, and antiretroviral therapy combination regimen were considered in this study. Kaplan–Meier models were used to estimate the univariate time-to-LTFU and Cox proportional hazards models to identify the multivariate predictors of LTFU. Results: Twenty-four percent (23.9% [301/1256]) of patients were lost to follow-up. Baseline CD4 count, year of enrolment, and drug combination were significant predictors of LTFU. Patients enrolled earlier (2008/2009) were twice as likely to be LTFU compared with those enrolled later (2010–2013). Gender and age did not significantly predict LTFU nor confound other predictors. Conclusion: The program showed higher LTFU rates than most studies in Nigeria and Africa, maybe due to difficulties with the access to the hospital and possible treatment fatigue. This study recommends the provision of transportation subsidies and proactive patient follow-up with “peer-tracking” to reduce LTFU among HIV infected patients, especially in resource-limited settings. PMID:27057373

CD4 Count in HIV- Brain-Dead Donors: Insight into Donor Risk Assessment for HIV+ Donors.

PubMed

Serrano, Oscar Kenneth; Kerwin, Scott; Payne, William D; Pruett, Timothy L

2017-04-01

The Human Immunodeficiency Virus (HIV) Organ Policy Equity Act allows for transplantation of organs from HIV-infected individuals (HIV+), provided it is performed under a research protocol. The safety assessment of an organ for transplantation is an essential element of the donation process. The risk for HIV-associated opportunistic infections increases as circulating CD4+ lymphocytes decrease to less than 200 cells/μL; however, the numbers of circulating CD4+ cells in the HIV-negative (HIV-) brain-dead donor (BDD) is not known. Circulating T-lymphocyte subset profiles in conventional HIV- BDD were measured in 20 BDD in a clinical laboratory. The mean age of the BDD cohort was 48.7 years, 95% were white and 45% were women. The average body mass index was 29.2 kg/m. Cerebrovascular accident (40%) was the most prevalent cause of death. Sixteen (80%) subjects had a CD4 count ≤441 cells/μL (lower limit of normal) and 11 (55%) had a CD4 count less than 200 cells/μL; 11 (55%) subjects had a CD8 count ≤125 cells/μL (lower limit of normal). CD4/CD8 ratio was below normal in 3 patients (normal, 1.4-2.6). No recipient had a recognized donor-associated adverse event. Absolute numbers of CD4 and CD8 T-lymphocytes are commonly reduced after brain death in HIV- individuals. Thus, CD4 absolute numbers are an inconsistent metric for assessing organ donor risk, irrespective of HIV status.

Effect of vitamin E-bonded dialyzer on eosinophilia in haemodialysis patients.

PubMed

Kojima, Kenichiro; Oda, Kuniyoshi; Homma, Hitoshi; Takahashi, Kazushi; Kanda, Yoshiko; Inokami, Taketoshi; Uchida, Shunya

2005-09-01

Eosinophilia in haemodialysis patients probably results from allergy to haemodialysis-related materials, including dialyzer membranes. We examined the effects of vitamin E-bonded dialyzers on eosinophil counts in haemodialysis patients. We enrolled seven patients who were on regular haemodialysis and had sustained eosinophilia. White blood cell, eosinophil, CD4- and CD8-positive lymphocyte counts, and serum interleukin-5 (IL-5) and IgE levels were determined before, 2 and 4 weeks after switching to vitamin E-bonded dialyzers. Eosinophil and CD4-positive lymphocyte counts and serum IL-5 were significantly (P = 0.003, 0.003 and 0.031, respectively) decreased after switching to vitamin E-bonded dialyzers. CD8-positive lymphocyte counts and serum IgE levels were unaltered. Crossover tests in two cases reproduced the higher eosinophilia within 4 weeks after returning to the original non-vitamin E-bonded dialyzer. Vitamin E-bonded dialyzers may ameliorate eosinophilia through a mechanism mediated by a decrease in IL-5 secretion by CD4-positive lymphocytes.

Salivary human beta defensins affected by oral Candida status in Chinese HIV/AIDS patients undergoing ART.

PubMed

Liu, Zhenmin; Yong, Xiangzhi; Jiang, Lanlan; Zhang, Linlin; Lin, Xuefang; Liu, Wei; Peng, Yuanyuan; Tao, Renchuan

2018-03-02

To observe relationships between oral Candida status and salivary human beta defensin-2 and -3 (hBD-2 and hBD-3) levels in HIV/AIDS patients of Guangxi, China during the first year of antiretroviral therapy (ART) dynamically, and to understand the influence of ART on oral Candida status and salivary hBDs expressions. A prospective self-controlled study was carried to observe the dynamic changes of CD4 + T cell counts, oral Candida carriages and salivary hBD-2,3 expressions in HIV/AIDS patients during the first year of ART. A total of 90 HIV/AIDS patients were enrolled, and were examined at the baseline, 3rd, 6th, 12th month of ART. Thirty healthy individuals were enrolled as control. Peripheral blood, oral rinse sample and unstimulated whole saliva were collected to test CD4 + T cell counts, oral Candida carriages and hBD-2,3 expressions. In the first year of ART, CD4 + T cell counts increased significantly. However, oral Candida carriages and oral candidiasis decreased significantly, and salivary hBD-2 expressions in HIV/AIDS patients decreased gradually, salivary hBD-3 levels were highly variable. Salivary hBD-2 concentrations were positively related to oral Candida carriages. The incidence of oral candidiasis among HIV/AIDS patients gradually decreased due to the immune reconstruction of ART. Salivary defensins might play an important role in Candida-host interaction in HIV/AIDS patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Motivational Interviewing and Cognitive-Behavioral Intervention to Improve HIV Medication Adherence Among Hazardous Drinkers

PubMed Central

Parsons, Jeffrey T.; Golub, Sarit A.; Rosof, Elana; Holder, Catherine

2009-01-01

Objective To assess the efficacy of a behavioral intervention designed to improve HIV medication adherence and reduce alcohol consumption among HIV-positive men and women. Design A randomized controlled trial conducted between July 2002 and August 2005. Setting A behavioral research center in New York City. Participants HIV-positive men and women (n = 143) who were on HIV antiretroviral medication and met criteria for hazardous drinking. Intervention Participants were randomly assigned to an 8-session intervention based on motivational interviewing and cognitive-behavioral skills building or a time- and content-equivalent educational condition. Outcome Measures Viral load, CD4 cell count, and self-reported adherence and drinking behavior were assessed at baseline and at 3- and 6-month follow-ups. Results Relative to the education condition, participants in the intervention demonstrated significant decreases in viral load and increases in CD4 cell count at the 3-month follow-up and significantly greater improvement in percent dose adherence and percent day adherence. There were no significant intervention effects for alcohol use, however, and effects on viral load, CD4 cell count, and adherence were not sustained at 6 months. Conclusions An 8-session behavioral intervention can result in improvement in self-report and biologic markers of treatment adherence and disease progression. This type of intervention should be considered for dissemination and integration into HIV clinics providing comprehensive care for HIV-positive persons with alcohol problems. Although the effect was attenuated over time, future studies might test the added effectiveness of booster sessions or ongoing adherence counseling. PMID:18077833

Impact of HIV Infection and Anti-Retroviral Therapy on the Immune Profile of and Microbial Translocation in HIV-Infected Children in Vietnam.

PubMed

Bi, Xiuqiong; Ishizaki, Azumi; Nguyen, Lam Van; Matsuda, Kazunori; Pham, Hung Viet; Phan, Chung Thi Thu; Ogata, Kiyohito; Giang, Thuy Thi Thanh; Phung, Thuy Thi Bich; Nguyen, Tuyen Thi; Tokoro, Masaharu; Pham, An Nhat; Khu, Dung Thi Khanh; Ichimura, Hiroshi

2016-08-02

CD4⁺ T-lymphocyte destruction, microbial translocation, and systemic immune activation are the main mechanisms of the pathogenesis of human immunodeficiency virus type 1 (HIV) infection. To investigate the impact of HIV infection and antiretroviral therapy (ART) on the immune profile of and microbial translocation in HIV-infected children, 60 HIV vertically infected children (31 without ART: HIV(+) and 29 with ART: ART(+)) and 20 HIV-uninfected children (HIV(-)) aged 2-12 years were recruited in Vietnam, and their blood samples were immunologically and bacteriologically analyzed. Among the HIV(+) children, the total CD4⁺-cell and their subset (type 1 helper T-cell (Th1)/Th2/Th17) counts were inversely correlated with age (all p < 0.05), whereas regulatory T-cell (Treg) counts and CD4/CD8 ratios had become lower, and the CD38⁺HLA (human leukocyte antigen)-DR⁺CD8⁺- (activated CD8⁺) cell percentage and plasma soluble CD14 (sCD14, a monocyte activation marker) levels had become higher than those of HIV(-) children by the age of 2 years; the CD4/CD8 ratio was inversely correlated with the plasma HIV RNA load and CD8⁺-cell activation status. Among the ART(+) children, the total CD4⁺-cell and Th2/Th17/Treg-subset counts and the CD4/CD8 ratio gradually increased, with estimated ART periods of normalization being 4.8-8.3 years, whereas Th1 counts and the CD8⁺-cell activation status normalized within 1 year of ART initiation. sCD14 levels remained high even after ART initiation. The detection frequency of bacterial 16S/23S ribosomal DNA/RNA in blood did not differ between HIV-infected and -uninfected children. Thus, in children, HIV infection caused a rapid decrease in Treg counts and the early activation of CD8⁺ cells and monocytes, and ART induced rapid Th1 recovery and early CD8⁺-cell activation normalization but had little effect on monocyte activation. The CD4/CD8 ratio could therefore be an additional marker for ART monitoring.

Regulation of oxidative stress in response to acute aerobic and resistance exercise in HIV-infected subjects: a case-control study.

PubMed

Deresz, L F; Sprinz, E; Kramer, A S; Cunha, G; de Oliveira, A R; Sporleder, H; de Freitas, D R J; Lazzarotto, A R; Dall'Ago, P

2010-11-01

Human immunodeficiency virus (HIV)-infected subjects have increased levels of oxidative stress which could impair immunological function and therefore contribute to the progression of AIDS. These characteristics are usually evaluated at rest and responses to exercise have yet to be evaluated. The aim of the present study was to assess the effect of a bout of aerobic exercise followed by resistance exercises on antioxidant system in HIV-infected and non-HIV subjects. There were included 14 cases (HIV-positive) and 14 controls (HIV-negative). The exercise protocol consisted of a single session of 20 minutes on a cycloergometer followed by a set of six resistance exercises. The activity of glutathione S-transferase (GST) and catalase were measured in plasma samples, total glutathione (TGSH) and thiobarbituric acid reactive substances (TBARS) were measured in erythrocytes. T CD4+ cells, T CD8+, viral load, complete blood count, and white blood count were also assessed. All measurements were performed at three times: baseline, after aerobic exercise, and after resistance exercises. At baseline, the HIV group had lower GST activity than controls, but after the exercise session GST values were similar in both groups. Compared to the control group TGSH was significantly lower in the HIV group at baseline, after aerobic and resistance exercises. The control group presented higher TBARS values after aerobic exercise compared to the HIV group. The neutrophil count was lower in the HIV group after aerobic and resistance exercises. These data indicate that HIV-infected subjects had lower antioxidant activity at rest. Physical exercise stimulated the enzymatic activity similarly in both groups.

The impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009–2011)

PubMed Central

Kaplan, Richard; Caldwell, Judy; Middelkoop, Keren; Bekker, Linda-Gail; MMed, Robin Wood

2014-01-01

Objective To identify determinants of TB case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. Methods Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients ≥15 yrs. Multivariable Cox proportional hazard models were used to determine risk factors for TB case fatality in these patients. Results In 2009, 2010 and 2011, 25,841, 26,104 and 25,554 newly registered adult TB patients were treated in primary health care clinics in Cape Town, of whom 49.7%, 50.4% and 50.9% were HIV-positive. ART uptake increased over the three years from 43% to 64.9% and case fatality of the HIV-positive patients decreased from 7.0% to 5.8% (p<0.001). Female gender, increasing age, retreatment TB, low CD4 counts and extrapulmonary TB (EPTB) were associated with increased case fatality while patients on ART had a substantial decrease in case fatality. The difference in case fatality between patients on ART and not on ART was most pronounced at low CD4 counts with the positive influence of ART noted up to a CD4 count threshold of 350 cells/mm3 (p<0.001). Despite improvements in ART uptake, in 2011, 21% of patients with CD4 counts <350 cells/mm3 did not start ART during TB treatment. Conclusion This study showed a relatively poor uptake of ART among severely immune-compromised TB patients. Patients with CD4 counts <350 cells/mm3 were shown to clearly benefit from ART during TB treatment and ART initiation should be prioritised for this category of patients. PMID:24820105

Impact of ART on TB case fatality stratified by CD4 count for HIV-positive TB patients in Cape Town, South Africa (2009-2011).

PubMed

Kaplan, Richard; Caldwell, Judy; Middelkoop, Keren; Bekker, Linda-Gail; Wood, Robin

2014-08-15

To identify determinants of tuberculosis (TB) case fatality including the impact of antiretroviral therapy (ART) at different CD4 thresholds for HIV-positive adult and adolescent TB patients. Through a retrospective analysis of the electronic TB database, we identified the HIV status of newly registered patients aged ≥15 years. Multivariable Cox proportional hazard models were used to determine the risk factors for TB case fatality in these patients. In 2009, 2010, and 2011, 25,841, 26,104, and 25,554 newly registered adult TB patients were treated in primary health care clinics in Cape Town, of whom 49.7%, 50.4%, and 50.9% were HIV positive. ART uptake increased over 3 years from 43% to 64.9%, and case fatality of the HIV-positive patients decreased from 7.0% to 5.8% (P < 0.001). Female gender, increasing age, retreatment TB, low CD4 counts, and extrapulmonary TB were associated with increased case fatality, whereas patients on ART had a substantial decrease in case fatality. The difference in case fatality between patients on ART and not on ART was most pronounced at low CD4 counts with the positive influence of ART noted up to a CD4 count threshold of 350 cells per cubic millimeter (P < 0.001). Despite improvements in ART uptake, in 2011, 21% of the patients with CD4 counts <350 cells per cubic millimeter did not start ART during TB treatment. This study showed a relatively poor uptake of ART among severely immune-compromised TB patients. Patients with CD4 counts <350 cells per cubic millimeter were shown to clearly benefit from ART during TB treatment, and ART initiation should be prioritized for this category of patients.

HIV Patients Drop Out in Indonesia: Associated Factors and Potential Productivity Loss.

PubMed

Siregar, Adiatma Ym; Pitriyan, Pipit; Wisaksana, Rudi

2016-07-01

this study reported various factors associated with a higher probability of HIV patients drop out, and potential productivity loss due to HIV patients drop out. we analyzed data of 658 HIV patients from a database in a main referral hospital in Bandung city, West Java, Indonesia from 2007 to 2013. First, we utilized probit regression analysis and included, among others, the following variables: patients' status (active or drop out), CD4 cell count, TB and opportunistic infection (OI), work status, sex, history of injecting drugs, and support from family and peers. Second, we used the drop out data from our database and CD 4 cell count decline rate from another study to estimate the productivity loss due to HIV patients drop out. lower CD4 cell count was associated with a higher probability of drop out. Support from family/peers, living with family, and diagnosed with TB were associated with lower probability of drop out. The productivity loss at national level due to treatment drop out (consequently, due to CD4 cell count decline) can reach US$365 million (using average wage). first, as lower CD 4 cell count was associated with higher probability of drop out, we recommend (to optimize) early ARV initiation at a higher CD 4 cell count, involving scaling up HIV service at the community level. Second, family/peer support should be further emphasized to further ensure treatment success. Third, dropping out from ART will result in a relatively large productivity loss.

HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality

PubMed Central

Serrano-Villar, Sergio; Sainz, Talia; Lee, Sulggi A.; Hunt, Peter W.; Sinclair, Elizabeth; Shacklett, Barbara L.; Ferre, April L.; Hayes, Timothy L.; Somsouk, Ma; Hsue, Priscilla Y.; Van Natta, Mark L.; Meinert, Curtis L.; Lederman, Michael M.; Hatano, Hiroyu; Jain, Vivek; Huang, Yong; Hecht, Frederick M.; Martin, Jeffrey N.; McCune, Joseph M.; Moreno, Santiago; Deeks, Steven G.

2014-01-01

A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART) fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3) is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+) and senescence (CD28− and CD57+CD28−), and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years). After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions. PMID:24831517

Hepatitis A vaccine response in HIV-infected patients: are TWINRIX and HAVRIX interchangeable?

PubMed

Jimenez, Humberto R; Hallit, Rabih R; Debari, Vincent A; Slim, Jihad

2013-02-18

Hepatitis A virus (HAV) infection remains a health risk for human immunodeficiency virus (HIV)-infected persons. Seroconversion rates among HAV vaccinated HIV-infected patients have been shown to be reduced compared to the general population. Current guidelines regard HAV vaccines as interchangeable, however there no published data comparing their efficacy in HIV patients. Our study evaluated the impact of different factors, including type of vaccination, on the immunologic response to hepatitis A vaccination in HIV-infected patients in the HAART era. This was a retrospective review of 226 HIV-infected patients at our clinic in Newark, NJ. Patients were eligible if at least one dose HAVRIX (1440 ELISA units) or TWINRIX (720 ELISA units) was administered and had anti-HAV antibody data pre- and post-vaccination. Numerous variables were evaluated for their effect on seroconversion. Seroconversion developed in 53.5% of the population. Responders had higher baseline median CD4 counts (446 versus 362 cells/mm(3); P=0.004) and lower median HIV RNA levels (475 copies/mL versus 5615 copies/mL; P=0.018) than non-responders. Patients with CD4 counts>350 cell/mm(3) were more likely to respond than those with CD4 counts<200 cell/mm(3), 60% and 35%, respectively (P=0.0498). Responders were also more likely to be virologically suppressed (48% versus 32%; P=0.0024). TWINRIX recipients had a 7-fold increased probability of seroconversion when virologically suppressed and less likely to respond if the vaccination series was not completed (OR 0.42; 95% CI 0.18-0.96). Seroconversion rates to HAV vaccination are significantly impaired among HIV-infected patients. CD4 cell count and virologic suppression at vaccination impact response. Seroconversion among TWINRIX recipients appeared to be more sensitive to these factors and vaccine series completion in comparison to those administered HAVRIX. Among HIV-patients requiring hepatitis a and b vaccination, the advantage of TWINRIX over HAVRIX as a combination product should be reevaluated. Copyright © 2012 Elsevier Ltd. All rights reserved.

Identifying risk factors of immune reconstitution inflammatory syndrome in AIDS patients receiving highly active anti-retroviral therapy.

PubMed

He, Bo; Zheng, Yuhuang; Liu, Meng; Zhou, Guoqiang; Chen, Xia; Mamadou, Diallo; He, Yan; Zhou, Huaying; Chen, Zi

2013-01-01

Immune reconstitution inflammation syndrome typically occurs within days after patients undergo highly active anti-retroviral therapy and is a big hurdle for effective treatment of AIDS patients. In this study, we monitored immune reconstitution inflammation syndrome occurrence in 238 AIDS patients treated with highly active anti-retroviral therapy. Among them, immune reconstitution inflammation syndrome occurred in 47 cases (19.7%). Immune reconstitution inflammation syndrome patients had significantly higher rate of opportunistic infection (p<0.001) and persistently lower CD4(+) cell count (p<0.001) compared to the non-immune reconstitution inflammation syndrome patients. In contrast, no significant differences in HIV RNA loads were observed between the immune reconstitution inflammation syndrome group and non-immune reconstitution inflammation syndrome group. These data suggest that a history of opportunistic infection and CD4(+) cell counts at baseline may function as risk factors for immune reconstitution inflammation syndrome occurrence in AIDS patients as well as potential prognostic markers. These findings will improve the management of AIDS with highly active anti-retroviral therapy. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Associations of Genetically Determined Continental Ancestry with CD4+ Count and Plasma HIV-1 RNA beyond Self-Reported Race and Ethnicity

PubMed Central

Brummel, Sean S; Singh, Kumud K; Maihofer, Adam X.; Farhad, Mona; Qin, Min; Fenton, Terry; Nievergelt, Caroline M.; Spector, Stephen A.

2015-01-01

Background Ancestry informative markers (AIMs) measure genetic admixtures within an individual beyond self-reported racial/ethnic (SRR) groups. Here, we used genetically determined ancestry (GDA) across SRR groups and examine associations between GDA and HIV-1 RNA and CD4+ counts in HIV-positive children in the US. Methods 41 AIMs, developed to distinguish 7 continental regions, were detected by real-time-PCR in 994 HIV-positive, antiretroviral naïve children. GDA was estimated comparing each individual’s genotypes to allele frequencies found in a large set of reference individuals originating from global populations using STRUCTURE. The means of GDA were calculated for each category of SRR. Linear regression was used to model GDA on CD4+ count and log10 RNA, adjusting for SRR and age. Results Subjects were 61% Black, 25% Hispanic, 13% White and 1.3% Unknown. The mean age was 2.3 years (45% male), mean CD4+ count 981 cells/mm3, and mean log10 RNA 5.11. Marked heterogeneity was found for all SRR groups with high admixture for Hispanics. In adjusted linear regression models, subjects with 100% European ancestry were estimated to have 0.33 higher log10 RNA levels (95% CI: (0.03, 0.62), p=0.028) and 253 CD4+ cells /mm3 lower (95% CI: (−517, 11), p = 0.06) in CD4+ count, compared to subjects with 100% African ancestry. Conclusion Marked continental admixture was found among this cohort of HIV-infected children from the US. GDA contributed to differences in RNA and CD4+ counts beyond SRR, and should be considered when outcomes associated with HIV infection are likely to have a genetic component. PMID:26536313

A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1 infected women

PubMed Central

Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M.

2014-01-01

Background In HIV-1 infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy (ART), it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. Methods In a prospective study among 2269 HIV-1 infected ART-naïve women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum and non-pregnant periods. Results Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% CI 39-73) cells/mm3 lower during pregnant compared to non-pregnant periods and 70 (95% CI 53-88) cells/mm3 lower during pregnant compared to postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and non-pregnant periods (p=0.9) or pregnant and postpartum periods (p=0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared to non-pregnant periods. Conclusion CD4 count declines among HIV-1 infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short term impact on plasma HIV-1 RNA concentrations. PMID:24442226

A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women.

PubMed

Heffron, Renee; Donnell, Deborah; Kiarie, James; Rees, Helen; Ngure, Kenneth; Mugo, Nelly; Were, Edwin; Celum, Connie; Baeten, Jared M

2014-02-01

In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression. In a prospective study among 2269 HIV-1-infected antiretroviral therapy-naive women from 7 African countries, we examined the effect of pregnancy on HIV-1 disease progression. We used linear mixed models to compare CD4 counts and plasma HIV-1 RNA concentrations between pregnant, postpartum, and nonpregnant periods. Women contributed 3270 person-years of follow-up, during which time 476 women became pregnant. In adjusted analysis, CD4 counts were an average of 56 (95% confidence interval: 39 to 73) cells/mm lower during pregnant compared with nonpregnant periods and 70 (95% confidence interval: 53 to 88) cells/mm lower during pregnant compared with postpartum periods; these results were consistent when restricted to the subgroup of women who became pregnant. Plasma HIV-1 RNA concentrations were not different between pregnant and nonpregnant periods (P = 0.9) or pregnant and postpartum periods (P = 0.3). Neither CD4 counts nor plasma HIV-1 RNA levels were significantly different in postpartum compared with nonpregnant periods. CD4 count declines among HIV-1-infected women during pregnancy are temporary and not sustained in postpartum periods. Pregnancy does not have a short-term impact on plasma HIV-1 RNA concentrations.

Associations of Genetically Determined Continental Ancestry With CD4+ Count and Plasma HIV-1 RNA Beyond Self-Reported Race and Ethnicity.

PubMed

Brummel, Sean S; Singh, Kumud K; Maihofer, Adam X; Farhad, Mona; Qin, Min; Fenton, Terry; Nievergelt, Caroline M; Spector, Stephen A

2016-04-15

Ancestry informative markers (AIMs) measure genetic admixtures within an individual beyond self-reported racial/ethnic (SRR) groups. Here, we used genetically determined ancestry (GDA) across SRR groups and examine associations between GDA and HIV-1 RNA and CD4 counts in HIV-positive children in the United States. Forty-one AIMs, developed to distinguish 7 continental regions, were detected by real-time PCR in 994 HIV-positive, antiretroviral naive children. GDA was estimated comparing each individual's genotypes to allele frequencies found in a large set of reference individuals originating from global populations using STRUCTURE. The means of GDA were calculated for each category of SRR. Linear regression was used to model GDA on CD4 count and log10 RNA, adjusting for SRR and age. Subjects were 61% black, 25% Hispanic, 13% white, and 1.3% Unknown. The mean age was 2.3 years (45% male), mean CD4 count of 981 cells per cubic millimeter, and mean log10 RNA of 5.11. Marked heterogeneity was found for all SRR groups with high admixture for Hispanics. In adjusted linear regression models, subjects with 100% European ancestry were estimated to have 0.33 higher log10 RNA levels (95% CI: 0.03 to 0.62, P = 0.028) and 253 CD4 cells per cubic millimeter lower (95% CI: -517 to 11, P = 0.06) in CD4 count, compared to subjects with 100% African ancestry. Marked continental admixture was found among this cohort of HIV-infected children from the United States. GDA contributed to differences in RNA and CD4 counts beyond SRR and should be considered when outcomes associated with HIV infection are likely to have a genetic component.

Incidence and risk factors of severe adverse events with nevirapine-based antiretroviral therapy in HIV-infected women. MTCT-Plus program, Abidjan, Côte d'Ivoire

PubMed Central

2010-01-01

Background In resource-limited settings where nevirapine-containing regimen is the preferred regimen in women, data on severe adverse events (SAEs) according to CD4 cell count are limited. We estimated the incidence of SAEs according to CD4 cell count and identify their risk factors in nevirapine-treated women. Methods All HIV-infected women who initiated nevirapine-containing regimen in the MTCT-Plus operational program in Abidjan, Côte d'Ivoire, were eligible for this study. Laboratory and clinical (rash) SAEs were classified as grade 3 and 4. Cox models were used to identify factors associated with the occurrence of SAEs. Results From August 2003 to October 2006, 290 women initiated a nevirapine-containing regimen at a median CD4 cell count of 186 cells/mm3 (IQR 124-266). During a median follow-up on treatment of 25 months, the incidence of all SAEs was 19.5/100 patient-years. The 24-month probability of occurrence of hepatotoxicity or rash was not different between women with a CD4 cell count >250 cells/mm3 and women with a CD4 cell count ≤250 cells/mm3 (8.3% vs. 9.9%, Log-rank test: p = 0.75). In a multivariate proportional hazard model, neither CD4 cell count >250 cells/mm3 at treatment initiation nor initiation NVP-based regimen initiated during pregnancy were associated with the occurrence of SAEs. Conclusion CD4 cell count >250 cells/mm3 was not associated with a higher risk of severe hepatotoxicity and/or rash, as well as initiation of ART during pregnancy. Pharmacovogilance data as well as meta-analysis on women receiving NVP in these settings are needed for better information about NVP toxicity. PMID:20576111

A CD4+ cell count <200 cells per cubic millimeter at 2 years after initiation of combination antiretroviral therapy is associated with increased mortality in HIV-infected individuals with viral suppression.

PubMed

Loutfy, Mona R; Genebat, Miguel; Moore, David; Raboud, Janet; Chan, Keith; Antoniou, Tony; Milan, David; Shen, Anya; Klein, Marina B; Cooper, Curtis; Machouf, Nima; Rourke, Sean B; Rachlis, Anita; Tsoukas, Chris; Montaner, Julio S G; Walmsley, Sharon L; Smieja, Marek; Bayoumi, Ahmed; Mills, Edward; Hogg, Robert S

2010-12-01

To determine the long-term impact of immunologic discordance (viral load <50 copies/mL and CD4+ count <=200 cells/mm3) in antiretroviral-naive patients initiating combination antiretroviral therapy (cART). Our analysis included antiretroviral-naive individuals from a population-based Canadian Observational Cohort that initiated cART after January 1, 2000, and achieved virologic suppression. Multivariable Cox proportional hazards regression was used to examine the association between 1-year and 2-year immunologic discordance and time to death from all-causes. Correlates of immunologic discordance were assessed with logistic regression. Immunologic discordance was observed in 19.9% (404 of 2028) and 10.2% (176 of 1721) of individuals at 1 and 2 years after cART initiation, respectively. Two-year immunologic discordance was associated with an increased risk of death [adjusted hazard ratio = 2.69; 95% confidence interval (CI): 1.26 to 5.78]. One-year immunologic discordance was not associated with death (adjusted hazard ratio = 1.12; 95% CI: 0.54 to 2.30). Two-year immunologic discordance was associated with older age (aOR per decade = 1.23; 95% CI: 1.03 to 1.48), male gender (aOR = 1.86; 95% CI: 1.09 to 3.16), injection drug use (aOR = 2.75; 95% CI: 1.81 to 4.17), and lower baseline CD4+ count (aOR per 100 cells = 0.24; 95% CI: 0.19 to 0.31) and viral load (aOR per log10 copies/mL = 0.46; 95% CI: 0.33 to 0.65). Immunologic discordance after 2 years of cART in antiretroviral-naive individuals was significantly associated with an increased risk of mortality.

Effect of management strategies and clinical status on costs of care for advanced HIV.

PubMed

Barnett, Paul G; Chow, Adam; Joyce, Vilija R; Bayoumi, Ahmed M; Griffin, Susan C; Sun, Huiying; Holodniy, Mark; Brown, Sheldon T; Cameron, William; Sculpher, Mark; Youle, Mike; Anis, Aslam H; Owens, Douglas K

2014-05-01

To determine the association between preexisting characteristics and current health and the cost of different types of advanced human immunodeficiency virus (HIV) care. Treatment-experienced patients failing highly active antiretroviral treatment (ART) in the United States, Canada, and the United Kingdom were factorial randomized to an antiretroviral-free period and ART intensification. Cost was estimated by multiplying patient-reported utilization by a unit cost. A total of 367 participants were followed for a mean of 15.3 quarters (range 1-26). Medication accounted for most (61.8%) of the $26,832 annual cost. Cost averaged $4147 per quarter for ART, $1981 for inpatient care, $580 for outpatient care, and $346 for other medications. Cost for inpatient stays, outpatient visits, and other medications was 171% higher (P <.01) and cost of ART was 32% lower (P <.01) when cluster of differentiation 4 (CD4) count was <50 cells/μL compared with periods when CD4 count was >200 cells/μL. Some baseline characteristics, including low CD4 count, high viral load, and HIV from injection drug use with hepatitis C coinfection, had a sustained effect on cost. The association between health status and cost depended on the type of care. Indicators of poor health were associated with higher inpatient and concomitant medication costs and lower cost for ART medication. Although ART has supplanted hospitalization as the most important cost in HIV care, some patients continue to incur high hospitalization costs in periods when they are using less ART. The cost of interventions to improve the use of ART might be offset by the reduction of other costs.

Changes in CD4 count among persons living with HIV/AIDS following Hurricane Katrina.

PubMed

Robinson, William T; Wendell, Deborah; Gruber, DeAnn

2011-07-01

To examine the effects of Hurricane Katrina on the disease progression of persons living with HIV/AIDS (PLWH/A), CD4 counts during the 18 months immediately prior and subsequent to Katrina were obtained from the Louisiana Office of Public Health. PLWH/A were determined to be either non-residents of the New Orleans area, returning evacuees or evacuees who had returned to the area within 18 months. A mixed model repeated measures ANOVA showed significant effects for race, sex, age, year of diagnosis, and mode of exposure. A significant main effect for residence was found, as well as an interaction of residence by time of CD4 count (pre-Katrina vs. post-Katrina), indicating that, while non-returning evacuees had lower overall CD4 counts, the change in CD4 counts of non-returning evacuees dropped more sharply than those of the returning PLWH/A or non-residents. While these results point to a potential need for the population of PLWH/A who continue to be affected by Katrina, they also provide important data on the effect that large-scale disasters and stressful life events may have on individuals with chronic disease.

Clinical and demographic factors associated with low viral load in early untreated HIV infection in the INSIGHT Strategic Timing of AntiRetroviral Treatment trial

PubMed Central

Law, Matthew G; Achhra, Amit; Deeks, Steven G; Gazzard, Brian; Migueles, Stephen A; Novak, Richard M; Ristola, Matti

2014-01-01

Objectives A small subset of HIV-positive adults have low HIV RNA in the absence of therapy, sometimes for years. Clinical factors associated with low HIV RNA in early infection have not been well defined. Methods We assessed factors associated with low plasma HIV RNA level at study entry in the Strategic Timing of AntiRetroviral Treatment (START) trial. All START participants had a baseline HIV RNA assessment within 60 days prior to randomisation. The key covariables considered for this analysis were race, hepatitis B virus (HBV) and hepatitis C virus (HCV) status. We assessed factors associated with HIV RNA ≤50 and ≤400 copies/mL using logistic regression. Because of the strong association between region of randomisation and baseline low HIV RNA, analyses were stratified by region. Results We found that of 4676 eligible participants randomised in START with a baseline HIV RNA assessment, 113 (2.4%) had HIV RNA ≤50 copies/mL at baseline, and a further 257 (5.5%) between 51 and 400 copies/mL. We found that HIV exposure routes other than male homosexual contact, higher HDL levels, higher CD4 cell counts, and higher CD4:CD8 ratio were associated with increased odds of low HIV RNA. HCV antibody positivity was borderline statistically significantly associated with low HIV RNA. Race and HBV surface antigen positivity were not significantly associated with low HIV RNA. Conclusion In a modern cohort of early untreated HIV infection we found that HIV exposure routes other than male homosexual contact and higher HDL were associated with increased odds of low HIV RNA. PMID:25711322

CD8 T-Cell Expansion and Inflammation Linked to CMV Coinfection in ART-treated HIV Infection

PubMed Central

Freeman, Michael L.; Mudd, Joseph C.; Shive, Carey L.; Younes, Souheil-Antoine; Panigrahi, Soumya; Sieg, Scott F.; Lee, Sulggi A.; Hunt, Peter W.; Calabrese, Leonard H.; Gianella, Sara; Rodriguez, Benigno; Lederman, Michael M.

2016-01-01

Background. Persistent CD8 T-cell expansion, low CD4/CD8 T-cell ratios, and heightened inflammation persist in antiretroviral therapy (ART)-treated human immunodeficiency virus (HIV) infection and are associated with increased risk of morbid outcomes. We explored the role of cytomegalovirus (CMV) infection in CD8 lymphocytosis and inflammation in ART-treated HIV infection. Methods. Absolute CD4 and CD8 T-cell counts were abstracted from clinical records and compared among 32 HIV-infected CMV-seronegative subjects, 126 age, CD4 and gender-matched HIV-infected CMV-seropositive subjects, and among 21 HIV-uninfected controls (9 CMV-negative, 12 CMV-positive). Plasma inflammatory indices were measured in a subset by ELISA. Results. Median CD8 counts/µL were higher in HIV-positive/CMV-positive patients (795) than in HIV-positive/CMV-negative subjects (522, P = .006) or in healthy controls (451, P = .0007), whereas CD8 T-cell counts were similar to controls' levels in HIV-positive/CMV-negative subjects. Higher plasma levels of IP-10 (P = .0011), TNF-RII (P = .0002), and D-dimer (P = .0444) were also found in coinfected patients than in HIV-positive/CMV-negative subjects. Conclusions. CMV infection is associated with higher CD8 T-cell counts, resultant lower CD4/CD8 ratios, and increased systemic inflammation in ART-treated HIV infection. CMV infection may contribute to risk for morbid outcomes in treated HIV infection. PMID:26400999

Mortality and loss to follow-up among HIV-infected persons on long-term antiretroviral therapy in Latin America and the Caribbean

PubMed Central

Carriquiry, Gabriela; Fink, Valeria; Koethe, John Robert; Giganti, Mark Joseph; Jayathilake, Karu; Blevins, Meridith; Cahn, Pedro; Grinsztejn, Beatriz; Wolff, Marcelo; Pape, Jean William; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; McGowan, Catherine Carey; Shepherd, Bryan Earl

2015-01-01

Introduction Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). Methods We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63–2.32) for 50 vs. 350 cells/µL; p<0.001) and older age (HR=1.47 (95% CI 1.29–1.69) for 50 vs. 30 years at ART initiation; p<0.001). Conclusions In this large, long-term study of mortality among HIV-positive adults initiating ART in Latin America and the Caribbean, overall estimates of mortality were heterogeneous, generally falling between those reported in high-income countries and sub-Saharan Africa. PMID:26165322

CD4 decline is associated with increased risk of cardiovascular disease, cancer, and death in virally suppressed patients with HIV.

PubMed

Helleberg, Marie; Kronborg, Gitte; Larsen, Carsten S; Pedersen, Gitte; Pedersen, Court; Obel, Niels; Gerstoft, Jan

2013-07-01

The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer. Patients with human immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995-2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline as a time-updated variable. We followed 2584 virally suppressed HIV patients for 13 369 person-years (PY; median observation time, 4.7 years). Fifty-six patients developed CD4 decline (incidence rate, 4.2/1000 PY [95% confidence interval {CI}, 3.2-5.4]). CD4 counts dropped from a median of 492 cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate ratio, 11.7 [95% CI, 3.6-37.4] and 13.7 [95% CI, 4.3-43.6], respectively, and mortality rate ratio 4.3 [95% CI, 1.1-17.6]). A major decline in CD4 count is associated with a marked increased risk of cardiovascular disease, cancer, and death among virally suppressed HIV patients.

Evaluation of treatment outcomes for patients on first-line regimens in US President's Emergency Plan for AIDS Relief (PEPFAR) clinics in Uganda: predictors of virological and immunological response from RV288 analyses.

PubMed

Crawford, K W; Wakabi, S; Magala, F; Kibuuka, H; Liu, M; Hamm, T E

2015-02-01

Viral load (VL) monitoring is recommended, but seldom performed, in resource-constrained countries. RV288 is a US President's Emergency Plan for AIDS Relief (PEPFAR) basic programme evaluation to determine the proportion of patients on treatment who are virologically suppressed and to identify predictors of virological suppression and recovery of CD4 cell count. Analyses from Uganda are presented here. In this cross-sectional, observational study, patients on first-line antiretroviral therapy (ART) (efavirenz or nevirapine+zidovudine/lamivudine) from Kayunga District Hospital and Kagulamira Health Center were randomly selected for a study visit that included determination of viral load (HIV-1 RNA), CD4 cell count and clinical chemistry tests. Subjects were recruited by time on treatment: 6-12, 13-24 or >24 months. Logistic regression modelling identified predictors of virological suppression. Linear regression modelling identified predictors of CD4 cell count recovery on ART. We found that 85.2% of 325 subjects were virologically suppressed (viral load<47 HIV-1 RNA copies/ml). There was no difference in the proportion of virologically suppressed subjects by time on treatment, yet CD4 counts were higher in each successive stratum. Women had higher median CD4 counts than men overall (406 vs. 294 cells/μL, respectively; P<0.0001) and in each time-on-treatment stratum. In a multivariate logistic regression model, predictors of virological suppression included efavirenz use [odds ratio (OR) 0.47; 95% confidence interval (CI) 0.22-1.02; P=0.057], lower cost of clinic visits (OR 0.815; 95% CI 0.66-1.00; P=0.05), improvement in CD4 percentage (OR 1.06; 95% CI 1.014-1.107; P=0.009), and care at Kayunga vs. Kangulamira (OR 0.47; 95% CI 0.23-0.92; P=0.035). In a multivariate linear regression model of covariates associated with CD4 count recovery, time on highly active antiretroviral therapy (ART) (P<0.0001), patient satisfaction with care (P=0.038), improvements in total lymphocyte count (P<0.0001) and haemoglobin concentration (P=0.05) were positively associated, whereas age at start of ART (P=0.0045) was negatively associated with this outcome. High virological suppression rates are achievable on first-line ART in Uganda. The odds of virological suppression were positively associated with efavirenz use and improvements in CD4 cell percentage and total lymphocyte count and negatively associated with the cost of travel to the clinic. CD4 cell reconstitution was positively associated with CD4 count at study visit, time on ART, satisfaction with care at clinic, haemoglobin concentration and total lymphocyte count and negatively associated with age. © 2014 British HIV Association.

CD4 criteria improves the sensitivity of a clinical algorithm developed to identify viral failure in HIV-positive patients on antiretroviral therapy

PubMed Central

Evans, Denise H; Fox, Matthew P; Maskew, Mhairi; McNamara, Lynne; MacPhail, Patrick; Mathews, Christopher; Sanne, Ian

2014-01-01

Introduction Several studies from resource-limited settings have demonstrated that clinical and immunologic criteria are poor predictors of virologic failure, confirming the need for viral load monitoring or at least an algorithm to target viral load testing. We used data from an electronic patient management system to develop an algorithm to identify patients at risk of viral failure using a combination of accessible and inexpensive markers. Methods We analyzed data from HIV-positive adults initiated on antiretroviral therapy (ART) in Johannesburg, South Africa, between April 2004 and February 2010. Viral failure was defined as ≥2 consecutive HIV-RNA viral loads >400 copies/ml following suppression ≤400 copies/ml. We used Cox-proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Weights for each predictor associated with virologic failure were created as the sum of the natural logarithm of the adjusted HR and dichotomized with the optimal cut-off at the point with the highest sensitivity and specificity (i.e. ≤4 vs. >4). We assessed the diagnostic accuracy of predictor scores cut-offs, with and without CD4 criteria (CD4 <100 cells/mm3; CD4 < baseline; >30% drop in CD4), by calculating the proportion with the outcome and the observed sensitivity, specificity, positive and negative predictive value of the predictor score compared to the gold standard of virologic failure. Results We matched 919 patients with virologic failure (1:3) to 2756 patients without. Our predictor score included variables at ART initiation (i.e. gender, age, CD4 count <100 cells/mm3, WHO stage III/IV and albumin) and laboratory and clinical follow-up data (drop in haemoglobin, mean cell volume (MCV) <100 fl, CD4 count <200 cells/mm3, new or recurrent WHO stage III/IV condition, diagnosis of new condition or symptom and regimen change). Overall, 51.4% had a score 51.4% had a score ≥4 and 48.6% had a score <4. A predictor score including CD4 criteria performed better than a score without CD4 criteria and better than WHO clinico-immunological criteria or WHO clinical staging to predict virologic failure (sensitivity 57.1% vs. 40.9%, 25.2% and 20.9%, respectively). Conclusions Predictor scores or risk categories, with CD4 criteria, could be used to identify patients at risk of virologic failure in resource-limited settings so that these patients may be targeted for focused interventions to improve HIV treatment outcomes. PMID:25227265

C-Reactive Protein (CRP), Interferon Gamma-Inducible Protein 10 (IP-10), and Lipopolysaccharide (LPS) Are Associated with Risk of Tuberculosis after Initiation of Antiretroviral Therapy in Resource-Limited Settings

PubMed Central

Tenforde, Mark W.; Gupte, Nikhil; Dowdy, David W.; Asmuth, David M.; Balagopal, Ashwin; Pollard, Richard B.; Sugandhavesa, Patcharaphan; Lama, Javier R.; Pillay, Sandy; Cardoso, Sandra W.; Pawar, Jyoti; Santos, Breno; Riviere, Cynthia; Mwelase, Noluthando; Kanyama, Cecilia; Kumwenda, Johnstone; Hakim, James G.; Kumarasamy, Nagalingeswaran; Bollinger, Robert; Semba, Richard D.; Campbell, Thomas B.; Gupta, Amita

2015-01-01

Objective The association between pre-antiretroviral (ART) inflammation and immune activation and risk for incident tuberculosis (TB) after ART initiation among adults is uncertain. Design Nested case-control study (n = 332) within ACTG PEARLS trial of three ART regimens among 1571 HIV-infected, treatment-naïve adults in 9 countries. We compared cases (participants with incident TB diagnosed by 96 weeks) to a random sample of controls (participants who did not develop TB, stratified by country and treatment arm). Methods We measured pre-ART C-reactive protein (CRP), EndoCab IgM, ferritin, interferon gamma (IFN-γ), interleukin 6 (IL-6), interferon gamma-inducible protein 10 (IP-10), lipopolysaccharide (LPS), soluble CD14 (sCD14), tumor necrosis factor alpha (TNF-α), and CD4/DR+/38+ and CD8/DR+/38+ T cells. Markers were defined according to established cutoff definitions when available, 75th percentile of measured values when not, and detectable versus undetectable for LPS. Using logistic regression, we measured associations between biomarkers and incident TB, adjusting for age, sex, study site, treatment arm, baseline CD4 and log10 viral load. We assessed the discriminatory value of biomarkers using receiver operating characteristic (ROC) analysis. Results Seventy-seven persons (4.9%) developed incident TB during follow-up. Elevated baseline CRP (aOR 3.25, 95% CI: 1.55–6.81) and IP-10 (aOR 1.89, 95% CI: 1.05–3.39), detectable plasma LPS (aOR 2.39, 95% CI: 1.13–5.06), and the established TB risk factors anemia and hypoalbuminemia were independently associated with incident TB. In ROC analysis, CRP, albumin, and LPS improved discrimination only modestly for TB risk when added to baseline routine patient characteristics including CD4 count, body mass index, and prior TB. Conclusion Incident TB occurs commonly after ART initiation. Although associated with higher post-ART TB risk, baseline CRP, IP-10, and LPS add limited value to routine patient characteristics in discriminating who develops active TB. Besides determining ideal cutoffs for these biomarkers, additional biomarkers should be sought that predict TB disease in ART initiators. PMID:25719208

CD4+ memory T cells retain surface expression of CD31 independently of thymic function in patients with lymphoproliferative disorders following autologous hematopoietic stem-cell transplantation.

PubMed

Batorov, Egor V; Tikhonova, Marina A; Kryuchkova, Irina V; Sergeevicheva, Vera V; Sizikova, Svetlana A; Ushakova, Galina Y; Batorova, Dariya S; Gilevich, Andrey V; Ostanin, Alexander A; Shevela, Ekaterina Y; Chernykh, Elena R

2017-07-01

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation (AHSCT) causes severe and long-lasting immunodeficiency in patients with lymphoproliferative disorders. The thymus begins to restore the T-cell repertoire approximately from the sixth month post-transplant. We assessed the dynamics of post-transplant recovery of CD4 + CD45RA + CD31 + T cells, "recent thymic emigrants" (RTEs), and a poorly described subtype of CD4 + CD45RA - CD31 + T cells in 90 patients with lymphoproliferative disorders following high-dose chemotherapy with AHSCT. Relative and absolute counts of CD4 + CD31 + naïve and memory T cells were evaluated before AHSCT, at the day of engraftment, and 6- and 12-month post-transplant. The pre-transplant count of CD4 + CD45RA + CD31 + T cells was lower than in healthy controls, and did not reach donors' values during the 12-month period. The pre-transplant number of CD4 + CD45RA - CD31 + T cells was higher than in healthy controls and was restored rapidly following AHSCT. Post-transplant mediastinal radiotherapy reduced counts of RTEs and elongated recovery period. Non-thymic tissue irradiation did not reduce this subset. The obtained data indicate that homeostatic proliferation may decrease the significance of CD31 expression on CD4 + CD45RA + T cells as a marker of RTEs, and suggest that evaluation of RTEs recovery by flow cytometry requires an accurate gating strategy to exclude CD31 + memory T cells.

CD4/CD8 Ratio Predicts Yellow Fever Vaccine-Induced Antibody Titers in Virologically Suppressed HIV-Infected Patients.

PubMed

Avelino-Silva, Vivian Iida; Miyaji, Karina Takesaki; Mathias, Augusto; Costa, Dayane Alves; de Carvalho Dias, Juliana Zanatta; Lima, Sheila Barbosa; Simoes, Marisol; Freire, Marcos S; Caiaffa-Filho, Helio H; Hong, Marisa A; Lopes, Marta H; Sartori, Ana M; Kallas, Esper G

2016-02-01

Yellow fever vaccine (YFV) induces weaker immune responses in HIV-infected individuals. However, little is known about YFV responses among antiretroviral-treated patients and potential immunological predictors of YFV response in this population. We enrolled 34 antiretroviral therapy (ART)-treated HIV-infected and 58 HIV-uninfected adults who received a single YFV dose to evaluate antibody levels and predictors of immunity, focusing on CD4(+) T-cell count, CD4(+)/CD8(+) ratio, and Human Pegivirus (GBV-C) viremia. Participants with other immunosuppressive conditions were excluded. Median time since YFV was nonsignificantly shorter in HIV-infected participants than in HIV-uninfected participants (42 and 69 months, respectively, P = 0.16). Mean neutralizing antibody (NAb) titers was lower in HIV-infected participants than HIV-uninfected participants (3.3 vs. 3.6 log10mIU/mL, P = 0.044), a difference that remained significant after adjustment for age, sex, and time since vaccination (P = 0.024). In HIV-infected participants, lower NAb titers were associated with longer time since YFV (rho: -0.38, P = 0.027) and lower CD4(+)/CD8(+) ratio (rho: 0.42, P = 0.014), but not CD4(+) T-cell count (P = 0.52). None of these factors were associated with NAb titers in HIV-uninfected participant. GBV-C viremia was not associated with difference in NAb titers overall or among HIV-infected participants. ART-treated HIV-infected individuals seem to have impaired and/or less durable responses to YFV than HIV-uninfected individuals, which were associated with lower CD4(+)/CD8(+) ratio, but not with CD4(+) T-cell count. These results supports the notion that low CD4(+)/CD8(+) ratio, a marker linked to persistent immune activation, is a better indicator of functional immune disturbance than CD4(+) T-cell count in patients with successful ART.

Improved employment and education outcomes in households of HIV-infected adults with high CD4 cell counts: evidence from a community health campaign in Uganda.

PubMed

Thirumurthy, Harsha; Chamie, Gabriel; Jain, Vivek; Kabami, Jane; Kwarisiima, Dalsone; Clark, Tamara D; Geng, Elvin; Petersen, Maya L; Charlebois, Edwin D; Kamya, Moses R; Havlir, Diane V

2013-02-20

There is limited evidence on the association between socioeconomic outcomes and CD4 counts in populations that include HIV-infected adults who have high CD4 counts or have not been diagnosed. We examined this association among adults in a rural Ugandan parish. A community health campaign offering diagnostic and treatment services for HIV and other diseases was conducted with Ministry of Health support. Data on campaign participants' education and employment were collected and a detailed household socioeconomic survey was conducted among a subset of participants. Regression analyses were used to assess relationships between CD4 count and employment and education outcomes. A total of 2323 adults (74% of the community) participated in the campaign; 179 of 2282 (7.8%) tested HIV-positive and 46% were newly diagnosed. Among HIV-infected adults not on antiretroviral therapy (ART), those with CD4 at least 500 worked 6.9 more days/month (P < 0.01; 39% more) and 2.5 more h per day (P < 0.05, 44% more) than those with CD4 less than 200. These effects were not significantly different from the effects for those with CD4 350-499. Children aged 6-11 years in households of adults with CD4 at least 350 did not have significantly different school enrollment rates than children in households of adults with CD4 less than 350, but differences were larger among children aged 12-18 years. Outcomes of HIV-infected adults with CD4 at least 350 were better than those of adults with CD4 less than 200 and resembled those of HIV-uninfected adults. The results suggest that early ART initiation may generate economic benefits by preventing a decline in socioeconomic status, but further research is needed to determine the CD4 threshold at which these benefits would be largest.

When to Start Antiretroviral Therapy in Children Aged 2–5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa

PubMed Central

Schomaker, Michael; Egger, Matthias; Ndirangu, James; Phiri, Sam; Moultrie, Harry; Technau, Karl; Cox, Vivian; Giddy, Janet; Chimbetete, Cleophas; Wood, Robin; Gsponer, Thomas; Bolton Moore, Carolyn; Rabie, Helena; Eley, Brian; Muhe, Lulu; Penazzato, Martina; Essajee, Shaffiq; Keiser, Olivia; Davies, Mary-Ann

2013-01-01

Background There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2–5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS–Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2–5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%. Methods and Findings ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1–6.5) (no ART) to 2.1% (95% CI: 1.3%–3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%–3.5%) and 2.2% (95% CI: 1.4%–3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. Conclusions The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm3 or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary PMID:24260029

Rituximab in refractory myasthenia gravis: extended prospective study results.

PubMed

Beecher, Grayson; Anderson, Dustin; Siddiqi, Zaeem A

2018-05-09

Rituximab appears beneficial in treatment-refractory myasthenia gravis (MG), however, prospective, long-term durability data is lacking. In this prospective, open-label study of rituximab in refractory MG, 22 patients (10 AChR, 9 MuSK, 3 seronegative) received rituximab at baseline, with repeat cycles driven by clinical worsening. Manual muscle testing (MMT) scores and CD19/CD20+ B cell counts were serially monitored. At mean follow-up of 28.8 ± 19.0 months (range=6-66 months), mean MMT scores declined from 10.6 ± 5.4 to 3.3 ± 3.1 (p<0.0001). Mean prednisone dose declined from 25.2 ± 15.1 mg/d to 7.3 ± 7.1 mg/d (p=0.002). Ten relapses occurred, with average time to first relapse of 17.1 ± 5.5 months (range=9-23 months). CD19/CD20+ count recovery did not predict relapse. Three patients experienced prolonged B cell depletion (range=24-45 months) after one cycle. Sustained clinical improvement was associated with rituximab after one cycle, with prolonged time to relapse and reduction in steroid dose. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Prevalence and predictors of cytomegalovirus retinitis in HIV-infected patients with low CD4 lymphocyte counts in Vietnam.

PubMed

Colby, Donn J; Vo, Diem Qh; Teoh, Stephen C; Tam, Nguyen T; Liem, Nguyen T; Lu, Doanh; Nguyen, Thi T; Cosimi, Lisa; Pollack, Todd; Libman, Howard

2014-06-01

We describe the results of a study to determine the prevalence and characteristics of cytomegalovirus (CMV) retinitis among HIV-infected patients in Vietnam. We conducted a cross-sectional prospective study of patients with CD4 lymphocyte count ≤100 cells/mm(3)recruited from public HIV clinics. The diagnosis was made by a trained ophthalmologist using slit lamp biomicroscopy and corroborated on fundus photography. A total of 201 patients were screened. The median age was 32 years, 77% were men, median CD4 count was 47 cells/mm(3), and 62% were on antiretroviral treatment. Prevalence of CMV retinitis was 7% (14/201, 95% CI 4-11%). CMV retinitis was not associated with age, gender, injection drug use, CD4 count, WHO clinical stage, or antiretroviral treatment status. Blurring of vision and reduced visual acuity <20/40 were associated with CMV retinitis, but only 29% of patients with the diagnosis reported blurry vision and only 64% had abnormal vision. On multivariate analysis, the sole predictor for CMV retinitis was decreased visual acuity (OR 22.8,p < 0.001). In Ho Chi Minh City, CMV retinitis was found in 7% of HIV-infected patients with low CD4. HIV-infected patients with a CD4 count <100/mm(3)or who develop blurring of vision in Vietnam should be screened for CMV retinitis. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

PubMed

Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

1999-02-04

Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported for immune recovery in adults after chemotherapy and bone marrow transplantation.

Frequency and impact of suboptimal immune recovery on first-line antiretroviral therapy within the International Epidemiologic Databases to Evaluate AIDS in East Africa

PubMed Central

Nakanjako, Damalie; Kiragga, Agnes N.; Musick, Beverly S.; Yiannoutsos, Constantin T.; Wools-Kaloustian, Kara; Diero, Lameck; Oyaro, Patrick; Lugina, Emanuel; Ssali, John C.; Kambugu, Andrew; Easterbrook, Philippa

2017-01-01

Objective To describe patterns of suboptimal immune recovery (SO-IR) and associated HIV-related-illnesses during the first 5 years following first-line antiretroviral therapy (ART) initiation across seven ART sites in East Africa. Design Retrospective analysis of data from seven ART clinical sites (three Uganda, two Kenya and two Tanzania). Methods SO-IR was described by proportions of ART-treated adults with CD4+ cell counts less than 200, less than 350 and less than 500 cells/μl. Kaplan–Meier survival analysis techniques were used to assess predictors of SO-IR, and incident rates of HIV-related illnesses at CD4+ cell counts less than 200, 200–350, 351–499, and >500 cells/μl, respectively. Results Overall 80 843 adults initiated non-nucleoside reverse transcriptase inhibitor-based first-line ART; 65% were women and median CD4+ cell count was 126 [interquartile range (IQR), 52–202] cells/μl. Cumulative probability of SO-IR <200 cells/μl, <350 cells/μl and <500 cells/μl, after 5 years, was 11, 38 and 63%, respectively. Incidence of HIV-related illnesses was higher among those with CD4+ cell counts less than 200 and 200–350 cells/μl, than those who achieved CD4 counts above these thresholds. The most common events, at CD4 <200 cells/μl, were pulmonary tuberculosis [incident rate 15.98 (15.47–16.51)/100 person-years at risk (PYAR), oral candidiasis [incident rate 12.5 (12.03–12.94)] and herpes zoster [incident rate 6.30 (5.99–6.64)] events/100 PYAR. With attainment of a CD4+ cell count level 200–350 cells/μl, there was a substantial reduction in events/100 PYAR – by 91% to 1.45 (1.29–1.63) for TB, by 94% to 0.75 (0.64–0.89) for oral candidiasis, by 84% to 0.99 (0.86–1.14) for Herpes Zoster, and by 78% to 1.22 (1.07–1.39) for chronic diarrhea. The incidence of all events decreased further with CD4 counts above these thresholds. Conclusion Around 40% of adults initiated on ART have suboptimal immune recovery with CD4 counts <350 cells/ml after five years. Such patients will require closer monitoring for both HIV-related and non-HIV-related clinical events. PMID:26959510

rhG-CSF in healthy donors: mobilization of peripheral hemopoietic progenitors and effect on peripheral blood leukocytes.

PubMed

Sica, S; Rutella, S; Di Mario, A; Salutari, P; Rumi, C; Ortu la Barbera, E; Etuk, B; Menichella, G; D'Onofrio, G; Leone, G

1996-08-01

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16 micrograms/kg/day was given to 9 healthy donors to recruit hemopoietic progenitors (HP) for allogeneic transplantation or donor leukocyte infusion. rhG-CSF was administered s.c. for 5 days. No side effects were encountered except for moderate bone pain and lumbago. Mobilization was effective, reaching a peak median value of 187 x 10(3) CD34+ cells/ml (range 51.2-1127) and 2170 x 10(3) colony-forming units-granulocyte macrophage (CFU-GM)/ml (range 1138-4190). Peak values were obtained at a median of 4 days of rhG-CSF and represented, respectively, a 13-fold and a 37-fold increase from baseline values (p = 0.0007 and p = 0.006). White blood cell (WBC) counts increased 6-fold from baseline values (p < 0.0007) and reached a median peak of 34 x 10(6)/ml (23.5-59). Polymorphonuclear (PMN), and mononuclear (MNC) cells increased 10-fold and 2-fold, respectively (p = 0.0039 and p = 0.0026) and reached a median peak of 32.1 x 10(6)/ml (18.2-52) and 4.42 x 10(6)/ml (3.14-12.42). Absolute lymphocyte and monocyte counts increased at peak day in all donors 1.5-fold and 5.7-fold from baseline values (p = 0.0017 and p = 0.0018). In 7 of 9 donors, lymphocyte subsets were analyzed in detail. CD3+ and CD19+ lymphocytes increased 1.5-fold and 3-fold, respectively (p = 0.032 for both). NK and activated T lymphocytes doubled at a median of 4 days of rhG-CSF (p = 0.032 and p = NS, respectively). Similar changes were observed in lymphocytes collected in leukapheresis product. T helper and T suppressor subsets displayed a similar increase. Thus, besides the anticipated priming effect on HP and PMN, rhG-CSF in healthy donors produced an unexpected and still unexplained modification of lymphocyte subsets in peripheral blood.

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda

PubMed Central

Jain, Vivek; Chang, Wei; Byonanebye, Dathan M.; Owaraganise, Asiphas; Twinomuhwezi, Ellon; Amanyire, Gideon; Black, Douglas; Marseille, Elliot; Kamya, Moses R.; Havlir, Diane V.; Kahn, James G.

2015-01-01

Background Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up. Methods Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing. Findings Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451–716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100–200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals. Conclusions In a Ugandan HIV clinic, ART delivery costs—including VL testing—for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions. PMID:26632823

Estimated Costs for Delivery of HIV Antiretroviral Therapy to Individuals with CD4+ T-Cell Counts >350 cells/uL in Rural Uganda.

PubMed

Jain, Vivek; Chang, Wei; Byonanebye, Dathan M; Owaraganise, Asiphas; Twinomuhwezi, Ellon; Amanyire, Gideon; Black, Douglas; Marseille, Elliot; Kamya, Moses R; Havlir, Diane V; Kahn, James G

2015-01-01

Evidence favoring earlier HIV ART initiation at high CD4+ T-cell counts (CD4>350/uL) has grown, and guidelines now recommend earlier HIV treatment. However, the cost of providing ART to individuals with CD4>350 in Sub-Saharan Africa has not been well estimated. This remains a major barrier to optimal global cost projections for accelerating the scale-up of ART. Our objective was to compute costs of ART delivery to high CD4+count individuals in a typical rural Ugandan health center-based HIV clinic, and use these data to construct scenarios of efficient ART scale-up. Within a clinical study evaluating streamlined ART delivery to 197 individuals with CD4+ cell counts >350 cells/uL (EARLI Study: NCT01479634) in Mbarara, Uganda, we performed a micro-costing analysis of administrative records, ART prices, and time-and-motion analysis of staff work patterns. We computed observed per-person-per-year (ppy) costs, and constructed models estimating costs under several increasingly efficient ART scale-up scenarios using local salaries, lowest drug prices, optimized patient loads, and inclusion of viral load (VL) testing. Among 197 individuals enrolled in the EARLI Study, median pre-ART CD4+ cell count was 569/uL (IQR 451-716). Observed ART delivery cost was $628 ppy at steady state. Models using local salaries and only core laboratory tests estimated costs of $529/$445 ppy (+/-VL testing, respectively). Models with lower salaries, lowest ART prices, and optimized healthcare worker schedules reduced costs by $100-200 ppy. Costs in a maximally efficient scale-up model were $320/$236 ppy (+/- VL testing). This included $39 for personnel, $106 for ART, $130/$46 for laboratory tests, and $46 for administrative/other costs. A key limitation of this study is its derivation and extrapolation of costs from one large rural treatment program of high CD4+ count individuals. In a Ugandan HIV clinic, ART delivery costs--including VL testing--for individuals with CD4>350 were similar to estimates from high-efficiency programs. In higher efficiency scale-up models, costs were substantially lower. These favorable costs may be achieved because high CD4+ count patients are often asymptomatic, facilitating more efficient streamlined ART delivery. Our work provides a framework for calculating costs of efficient ART scale-up models using accessible data from specific programs and regions.

Factors Associated with D-Dimer Levels in HIV-Infected Individuals

PubMed Central

Borges, Álvaro H.; O’Connor, Jemma L.; Phillips, Andrew N.; Baker, Jason V.; Vjecha, Michael J.; Losso, Marcelo H.; Klinker, Hartwig; Lopardo, Gustavo; Williams, Ian; Lundgren, Jens D.

2014-01-01

Background Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood. Methods In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol. Results Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels. Conclusions D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels. PMID:24626096

The effect of short G-CSF administration on the numbers and clonogenic efficiency of hematopoietic progenitor cells in bone marrow and peripheral blood of normal donors.

PubMed

Zaucha, J M; Knopińska-Posłuszny, W; Bieniaszewska, M; Myśliwski, A; Hellmann, A

2000-01-01

We have analysed the cellularity, the number of clonogenic cells and their clonogenic efficiency (the number of clonogenic cells/2 x 10(5) MNC) in peripheral blood (PB) and bone marrow (BM) during and after filgrastim (rhG-CSF) mobilization of CD34+ cells in 12 healthy donors for allogeneic stem cell donation. G-CSF was administrated subcutaneously for 5 consecutive days at a dose of 10 micrograms/kg/day. WBC, MNC, CD34+ cell counts, CFU-GM and BFU-E assays in PB were performed at baseline and then daily 12 hours after each G-CSF dose. BM was assayed before start (day 1) and after the last dose (day 6) of G-CSF. Results are given as medians, with ranges in parentheses. In PB the total WBC and MNC increased 7.4-fold (6.0-12.3) and 3.3-fold (1.5-9.4), respectively, reaching a peak of 49.4 x 10(9)/l (32.5-66.6) on day 6 for WBC and 6.28 x 10(9)/l (4.7-13.3) for MNC on day 5. CD34+ cell number reached a peak value of 48.0 x 10(6)/l (45.6-285) on day 6 whereas CFU-GM and BFU-E reached their peaks on day 5, 0.95 x 10(4)/ml (0.05-6.08) and 1.04 x 10(4)/ml, respectively. CFU-MIX, not detectable at baseline, reached a peak of 0.95 x 10(4)/ml (0.006-0.51) on day 5 as well. This was accompanied by an increase in CFU-GM, BFU-E and CFU-MIX clonogenic efficiency: 23-fold (3-150), 9.75-fold (2.2-27.8) and 20-fold (2.5-210), respectively. In BM the total WBC number increased 2.5-fold (1.3-4.9) from the baseline value of 52.6 x 10(9)/l (7.9-137.0) whereas the MNC count increased 2.0-fold (0.81-3.7) from a baseline of 13.6 x 10(9)/l (3.5-54.8). This was, however, not significant. The number of CD34+ cells increased significantly 2.9-fold (0.8-8.3). In 8 donors CFU-MIX were detectable before but not after G-CSF treatment. A similar decrease in CFU-GM and BFU-E clonogenic efficiency occurred but was not significant. CFU-GM and BFU-E numbers did not change. We conclude that the total body numbers of lineage committed progenitors increased during G-CSF administration, which indicate their proliferation in addition to mobilization. The effect of G-CSF on the number of more primitive progenitors in BM is less clear and needs further investigation.

Diversity of Human and Macaque Airway Immune Cells at Baseline and during Tuberculosis Infection

PubMed Central

Myers, Amy J.; Jarvela, Jessica; Flynn, JoAnne; Rutledge, Tara; Bonfield, Tracey

2016-01-01

Immune cells of the distal airways serve as “first responders” of host immunity to the airborne pathogen Mycobacterium tuberculosis (Mtb). Mtb infection of cynomolgus macaques recapitulates the range of human outcomes from clinically silent latent tuberculosis infection (LTBI) to active tuberculosis of various degrees of severity. To further advance the application of this model to human studies, we compared profiles of bronchoalveolar lavage (BAL) cells of humans and cynomolgus macaques before and after Mtb infection. A simple gating strategy effectively defined BAL T-cell and phagocyte populations in both species. BAL from Mtb-naive humans and macaques showed similar differential cell counts. BAL T cells of macaques were composed of fewer CD4+cells but more CD8+ and CD4+CD8+ double-positive cells than were BAL T cells of humans. The most common mononuclear phagocyte population in BAL of both species displayed coexpression of HLA-DR, CD206, CD11b, and CD11c; however, multiple phagocyte subsets displaying only some of these markers were observed as well. Macaques with LTBI displayed a marked BAL lymphocytosis that was not observed in humans with LTBI. In macaques, the prevalence of specific mononuclear phagocyte subsets in baseline BAL correlated with ultimate outcomes of Mtb infection (i.e., LTBI versus active disease). Overall, these findings demonstrate the comparability of studies of pulmonary immunity to Mtb in humans and macaques. They also indicate a previously undescribed complexity of airway mononuclear phagocyte populations that suggests further lines of investigation relevant to understanding the mechanisms of both protection from and susceptibility to the development of active tuberculosis within the lung. PMID:27509488

Monitoring of HIV treatment in seven countries in the WHO Region of the Americas

PubMed Central

Belaunzarán-Zamudio, Pablo F; Shepherd, Bryan E; Crabtree-Ramírez, Brenda E; Luz, Paula M; Grinsztejn, Beatriz; Cesar, Carina; Cahn, Pedro; Cortés, Claudia; Wolff, Marcelo; Pape, Jean W; Padgett, Denis; Gotuzzo, Eduardo; McGowan, Catherine; Sierra-Madero, Juan G

2015-01-01

Abstract Objective To determine the prevalence of adequate monitoring and the costs of measuring CD4+ T-lymphocytes (CD4+ cell) and human immunodeficiency virus (HIV) viral load in people receiving antiretroviral therapy (ART) in seven countries in the WHO Region of the Americas. Methods We obtained retrospective, longitudinal data for 14 476 adults who started a first ART regimen at seven HIV clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru between 2000 and 2011. We estimated the proportion of 180-day periods with adequate monitoring, which we defined as at least one CD4+ cell count and one viral load measurement. Factors associated with adequate monitoring were analysed using regression methods. The costs of the tests were estimated. Findings The median follow-up time was 50.4 months; the proportion of 180-day periods with adequate CD4+ cell counts was 69% while the proportion with adequate monitoring was 62%. Adequate monitoring was more likely in participants who were older, who started ART more recently, whose first regimen included a non-nucleoside reverse transcriptase inhibitor or who had a CD4+ cell count less than 200 cells/µl at ART initiation. The cost of one CD4+ cell count ranged from 7.37 United States dollars (US$) in Argentina to US$ 64.09 in Chile; the cost of one viral load measurement ranged from US$ 20.34 in Brazil to US$ 186.28 in Haiti. Conclusion In HIV-infected participants receiving ART in the WHO Region of the Americas, CD4+ cell count and viral load monitoring was often carried out less frequently than regional guidelines recommend. The laboratory costs of monitoring varied greatly. PMID:26478610

Monitoring of HIV treatment in seven countries in the WHO Region of the Americas.

PubMed

Belaunzarán-Zamudio, Pablo F; Caro-Vega, Yanink N; Shepherd, Bryan E; Crabtree-Ramírez, Brenda E; Luz, Paula M; Grinsztejn, Beatriz; Cesar, Carina; Cahn, Pedro; Cortés, Claudia; Wolff, Marcelo; Pape, Jean W; Padgett, Denis; Gotuzzo, Eduardo; McGowan, Catherine; Sierra-Madero, Juan G

2015-08-01

To determine the prevalence of adequate monitoring and the costs of measuring CD4+ T-lymphocytes (CD4+ cell) and human immunodeficiency virus (HIV) viral load in people receiving antiretroviral therapy (ART) in seven countries in the WHO Region of the Americas. We obtained retrospective, longitudinal data for 14 476 adults who started a first ART regimen at seven HIV clinics in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru between 2000 and 2011. We estimated the proportion of 180-day periods with adequate monitoring, which we defined as at least one CD4+ cell count and one viral load measurement. Factors associated with adequate monitoring were analysed using regression methods. The costs of the tests were estimated. The median follow-up time was 50.4 months; the proportion of 180-day periods with adequate CD4+ cell counts was 69% while the proportion with adequate monitoring was 62%. Adequate monitoring was more likely in participants who were older, who started ART more recently, whose first regimen included a non-nucleoside reverse transcriptase inhibitor or who had a CD4+ cell count less than 200 cells/µl at ART initiation. The cost of one CD4+ cell count ranged from 7.37 United States dollars (US$) in Argentina to US$ 64.09 in Chile; the cost of one viral load measurement ranged from US$ 20.34 in Brazil to US$ 186.28 in Haiti. In HIV-infected participants receiving ART in the WHO Region of the Americas, CD4+ cell count and viral load monitoring was often carried out less frequently than regional guidelines recommend. The laboratory costs of monitoring varied greatly.

Extensive brain masses and cavitary lung lesions associated with toxoplasmosis and acquired immunodeficiency syndrome.

PubMed

Ayoade, Folusakin; Todd, John; Al-Delfi, Firas; King, John

2017-10-01

Toxoplasmosis is an important cause of enhancing brain lesions in patients with acquired immunodeficiency syndrome (AIDS), and it is typically associated with low CD4-lymphocyte counts. Extensive toxoplasma encephalitis when the CD4-lymphocyte count is above 100 cells/µl is unusual. Cavitary lung lesions are also not typically associated with toxoplasmosis. Here, we present a case of toxoplasmosis associated with extensive brain masses and cavitary lung lesions, both of which improved with directed toxoplasmosis therapy, in an AIDS patient with a CD4 cell count of 120 cells/µl.

Does the covariance structure matter in longitudinal modelling for the prediction of future CD4 counts?

PubMed

Taylor, J M; Law, N

1998-10-30

We investigate the importance of the assumed covariance structure for longitudinal modelling of CD4 counts. We examine how individual predictions of future CD4 counts are affected by the covariance structure. We consider four covariance structures: one based on an integrated Ornstein-Uhlenbeck stochastic process; one based on Brownian motion, and two derived from standard linear and quadratic random-effects models. Using data from the Multicenter AIDS Cohort Study and from a simulation study, we show that there is a noticeable deterioration in the coverage rate of confidence intervals if we assume the wrong covariance. There is also a loss in efficiency. The quadratic random-effects model is found to be the best in terms of correctly calibrated prediction intervals, but is substantially less efficient than the others. Incorrectly specifying the covariance structure as linear random effects gives too narrow prediction intervals with poor coverage rates. Fitting using the model based on the integrated Ornstein-Uhlenbeck stochastic process is the preferred one of the four considered because of its efficiency and robustness properties. We also use the difference between the future predicted and observed CD4 counts to assess an appropriate transformation of CD4 counts; a fourth root, cube root and square root all appear reasonable choices.

Intestinal parasitic infections in relation to HIV/AIDS status, diarrhea and CD4 T-cell count.

PubMed

Assefa, Shimelis; Erko, Berhanu; Medhin, Girmay; Assefa, Zelalem; Shimelis, Techalew

2009-09-18

HIV infection has been modifying both the epidemiology and outcome of parasitic infections. Hence, this study was undertaken to determine the prevalence of intestinal parasitic infection among people with and without HIV infection and its association with diarrhea and CD4 T-cell count. A cross-sectional study was conducted at Hawassa Teaching and Referral Hospital focusing on HIV positive individuals, who gave blood for CD4 T-cell count at their first enrollment and clients tested HIV negative from November, 2008 to March, 2009. Data on socio-demographic factors and diarrhea status were obtained by interviewing 378 consecutive participants (214 HIV positive and 164 HIV negative). Stool samples were collected from all study subjects and examined for parasites using direct, formol-ether and modified acid fast stain techniques. The prevalence of any intestinal parasitic infection was significantly higher among HIV positive participants. Specifically, rate of infection with Cryptosporidium, I. belli, and S. stercoralis were higher, particularly in those with CD4 count less than 200 cells/microL. Diarrhea was more frequent also at the same lower CD4 T-cell counts. Immunodeficiency increased the risk of having opportunistic parasites and diarrhea. Therefore; raising patient immune status and screening at least for those treatable parasites is important.

Nasopharyngeal Pneumococcal Colonization and Impact of a Single Dose of 13-Valent Pneumococcal Conjugate Vaccine in Indian Children With HIV and Their Unvaccinated Parents.

PubMed

Arya, Bikas K; Bhattacharya, Sangeeta Das; Sutcliffe, Catherine G; Ganaie, Feroze; Bhaskar, Arun; Bhattacharyya, Subhasish; Niyogi, Swapan Kumar; Moss, William J; Panda, Samiran; Ravikumar, Kadahalli Lingegowda; Das, Ranjan Saurav; Mandal, Sutapa

2018-05-01

Human immunodeficiency virus (HIV) infection increases risk of invasive disease from Streptococcus pneumoniae. Pneumococcal conjugate vaccines (PCV) prevent invasive disease and acquisition of vaccine type (VT) pneumococcus in the nasopharynx. To look at the safety and impact of one dose of PCV13 on acquisition of VT pneumococcal carriage in Indian children with HIV. We conducted a cohort study in families of HIV-infected children (CLH) and families of HIV-uninfected children (HUC) in West Bengal. All children received one dose of PCV13. Nasopharyngeal swabs were collected from children and parents at baseline and 2 months after vaccination. One hundred and fifteen CLH and 47 HUC received one dose of PCV13. Fifty-eight percent of CLH were on antiretroviral therapy (ART), and the median nadir CD4 count was 287. There were no significant adverse events in either group. HUC had more VT colonization than CLH-55% versus 23% of all pneumococcal isolates. HIV infection doubled the risk of nonvaccine serotype colonization (P = 0.03). There was no difference in acquisition of VT isolates in CLH (4.4%) and HUC (4.5%) post-PCV13; however, older CLH (>5 years) had decreased clearance of VT strains. ART made no difference in pneumococcal colonization at baseline or after PCV13; however, CLH with higher nadir CD4 counts before starting ART were less likely to have VT colonization post-PCV13 (prevalence ratio, 0.2; 95% confidence interval: 0.1-0.5). While there was no difference in acquisition of VT nasopharyngeal carriage of pneumococcus in CLH and HUC after one dose of PCV13, earlier access to ART may impact response to PCV13 in CLH.

Determinants of Hepatitis A Vaccine Immunity in a Cohort of Human Immunodeficiency Virus-Infected Children Living in Switzerland

PubMed Central

Crisinel, Pierre Alex; Posfay-Barbe, Klara Maria; Aebi, Christoph; Cheseaux, Jean-Jacques; Kahlert, Christian; Rudin, Christoph; Nadal, David

2012-01-01

Vaccination in HIV-infected children is often less effective than in healthy children. The goal of this study was to assess vaccine responses to hepatitis A virus (HAV) in HIV-infected children. Children of the Swiss Mother and Child HIV Cohort Study (MoCHiV) were enrolled prospectively. Recommendations for initial, catch-up, and additional HAV immunizations were based upon baseline antibody concentrations and vaccine history. HAV IgG was assessed by enzyme-linked immunosorbent assay (ELISA) with a protective cutoff value defined as ≥10 mIU/ml. Eighty-seven patients were included (median age, 11 years; range, 3.4 to 21.2 years). Forty-two patients were seropositive (48.3%) for HAV. Among 45 (51.7%) seronegative patients, 36 had not received any HAV vaccine dose and were considered naïve. Vaccine responses were assessed after the first dose in 29/35 naïve patients and after the second dose in 33/39 children (25 initially naïve patients, 4 seronegative patients, and 4 seropositive patients that had already received 1 dose of vaccine). Seroconversion was 86% after 1 dose and 97% after 2 doses, with a geometric mean concentration of 962 mIU/ml after the second dose. A baseline CD4+ T cell count below 750 cells/μl significantly reduced the post-2nd-dose response (P = 0.005). Despite a high rate of seroconversion, patients with CD4+ T cell counts of <750/μl had lower anti-HAV antibody concentrations. This may translate into a shorter protection time. Hence, monitoring humoral immunity may be necessary to provide supplementary doses as needed. PMID:22933400

Screening for Cryptococcal Antigenaemia in Patients Accessing an Antiretroviral Treatment Program in South Africa

PubMed Central

Jarvis, Joseph N; Lawn, Stephen D; Vogt, Monica; Bangani, Nonzwakazi; Wood, Robin; Harrison, Thomas S

2009-01-01

Background Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen (CRAG) in patients enrolling in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of pre-emptive therapy. Methods In this retrospective study, CRAG was measured in stored plasma samples obtained from patients as they enrolled in a well characterised ART cohort in South Africa. The predictive value of screening for CRAG prior to ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined. Results Of 707 participants with a baseline median CD4 count of 97 (IQR 46-157) cells/μL, 46 (7%) had a positive CRAG. Antigenaemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART and in multivariate analysis was an independent predictor of mortality (AHR 3.2, 95%CI 1.5-6.6). Most (92%) cases of cryptococcal meningitis developed in patients with a CD4 count ≤100 cells/μL. In this sub-set of patients, a CRAG titre ≥1 in 8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no previous history of the disease. Conclusions CRAG screening prior to commencing ART in patients with a CD4 count ≤100 cells/μL is highly effective at identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted pre-emptive treatment strategy. PMID:19222372

Incidence and predictors of herpes zoster among antiretroviral therapy-naïve patients initiating HIV treatment in Johannesburg, South Africa

PubMed Central

Maskew, Mhairi; Ajayi, Toyin; Berhanu, Rebecca; Majuba, Pappie; Sanne, Ian; Fox, Matthew P.

2014-01-01

Summary Objectives To describe the characteristics of HIV-infected patients experiencing herpes zoster after antiretroviral therapy (ART) initiation and to describe the incidence and predictors of a herpes zoster diagnosis. Methods Adult patients initiating ART from April 2004 to September 2011 at the Themba Lethu Clinic in Johannesburg, South Africa were included. Patients were followed from ART initiation until the date of first herpes zoster diagnosis, or death, transfer, loss to follow-up, or dataset closure. Herpes zoster is described using incidence rates (IR) and predictors of herpes zoster are presented as subdistribution hazard ratios (sHR) and 95% confidence intervals (95% CI). Results Fifteen thousand and twenty-five patients were included; 62% were female, the median age was 36.6 years, and the median baseline CD4 count was 98 cells/mm3. Three hundred and forty patients (2.3%) experienced herpes zoster in a median of 26.1 weeks after ART initiation. Most (71.5%) occurred within 1 year of initiation, for a 1-year IR of 18.1/1000 person-years. In an adjusted model, patients with low CD4 counts (<50 vs. ≥200 cells/mm3; sHR: 1.71, 95% CI: 1.21–2.47) and with a prior episode of herpes zoster (sHR: 1.53, 95% CI: 0.97–2.28) were at increased risk of incident herpes zoster. Conclusions While only 2% of patients were diagnosed with herpes zoster in this cohort, patients with low CD4 counts and those with prior episodes of herpes zoster were at higher risk for a herpes zoster diagnosis. PMID:24680820

The impact of a food assistance program on nutritional status, disease progression, and food security among people living with HIV in Uganda.

PubMed

Rawat, Rahul; Faust, Elizabeth; Maluccio, John A; Kadiyala, Suneetha

2014-05-01

Although the last decade has seen increased access to antiretroviral therapy across the developing world, widespread food insecurity and undernutrition continue to compromise an effective response to the AIDS epidemic. Limited evidence exists on the potential benefit of food security and nutrition interventions to people living with HIV (PLHIV). We capitalized on an existing intervention to PLHIV in Uganda and conducted a prospective quasi-experimental study evaluating the impact of a monthly household food basket, provided to food insecure antiretroviral therapy-naive PLHIVs for 12 months. The outcomes of interest measured at baseline and follow-up were nutritional status [body mass index; mid-upper arm circumference and hemoglobin (Hb) concentrations], disease severity (CD4 count), and 2 measures of food security: diet quality (Individual Dietary Diversity Score) and food access (Household Food Insecurity Access Scale). We used difference-in-difference propensity score matching to examine the impact of food assistance. Over 12 months, food assistance significantly increased body mass index by 0.6 kg/m (P < 0.01) and mid-upper arm circumference by 6.7 mm (P < 0.05). We found no impact on CD4 count, Hb concentrations, or Individual Dietary Diversity Score. Restricting the analysis to individuals with CD4 counts of greater than 350 cells per microliter, there were significant impacts on Hb concentrations (1.0 g/dL; P < 0.05). At the household level, food assistance increased the Household Food Insecurity Access Scale, by 2.1 points (P < 0.01). This study demonstrates the potential for food assistance programming to be part of the standard of care for PLHIV in areas of widespread food insecurity.

Longitudinal assessment of associations between food insecurity, antiretroviral adherence and HIV treatment outcomes in rural Uganda.

PubMed

Weiser, Sheri D; Palar, Kartika; Frongillo, Edward A; Tsai, Alexander C; Kumbakumba, Elias; Depee, Saskia; Hunt, Peter W; Ragland, Kathleen; Martin, Jeffrey; Bangsberg, David R

2014-01-02

Food insecurity is a potentially important barrier to the success of antiretroviral therapy (ART) programs in resource-limited settings. We undertook a longitudinal study in rural Uganda to estimate the associations between food insecurity and HIV treatment outcomes. Longitudinal cohort study. Participants were from the Uganda AIDS Rural Treatment Outcomes study and were followed quarterly for blood draws and structured interviews. We measured food insecurity with the validated Household Food Insecurity Access Scale. Our primary outcomes were: ART nonadherence (adherence <90%) measured by visual analog scale; incomplete viral load suppression (>400 copies/ml); and low CD4 T-cell count (<350 cells/μl). We used generalized estimating equations to estimate the associations, adjusting for socio-demographic and clinical variables. We followed 438 participants for a median of 33 months; 78.5% were food insecure at baseline. In adjusted analyses, food insecurity was associated with higher odds of ART nonadherence [adjusted odds ratio (AOR) 1.56, 95% confidence interval (CI) 1.10-2.20, P < 0.05], incomplete viral suppression (AOR 1.52, 95% CI 1.18-1.96, P < 0.01), and CD4 T-cell count less than 350 (AOR 1.47, 95% CI 1.24-1.74, P < 0.01). Adding adherence as a covariate to the latter two models removed the association between food insecurity and viral suppression, but not between food insecurity and CD4 T-cell count. Food insecurity is longitudinally associated with poor HIV outcomes in rural Uganda. Intervention research is needed to determine the extent to which improved food security is causally related to improved HIV outcomes and to identify the most effective policies and programs to improve food security and health.

Micronutrients decrease incidence of common infections in type 2 diabetic outpatients.

PubMed

Liu, Yinghua; Jing, Hongjiang; Wang, Jin; Zhang, Rongxin; Zhang, Yuehong; Zhang, Yong; Xu, Qing; Yu, Xiaoming; Xue, Changyong

2011-01-01

A randomized, double-blind, placebo-controlled trial was carried out to investigate the effects of micronutrients supplementation on immunity and the incidence of common infections in type 2 diabetic outpatients. A total of 196 type 2 diabetic outpatients were randomized to receive tablets of micronutrients (n=97) or placebo (n=99) for 6 months. Individualized dietary energy intake and daily physical activity were recommended. Anthropometric measurements, blood biochemical variables and the incidence of common infections were measured at baseline and at 6 months. Data on diet, exercise and infection (upper respiratory tract infection, skin infection, urinary and genital tract infections, other infections) were recorded 1 month before the study and every month during the study. Blood concentrations of total protein, iron (Fe), folic acid and hemoglobin increased and unsaturated iron-binding capacity(UIBC) levels were decreased in the micronutrients supplementation group compared to the placebo group at 6 months. Moreover, at 6 months, compared to the placebo group, the blood concentrations of IgE, CD4+, CD4+/CD8+, WBC, lymphocyte counts, basophilic leukocyte increased and CD8+ count decreased in the supplementation group, and the levels of IgA, IgM, IgG and complements C3 and C4 did not differ. The incidence of upper respiratory infection, whitlow, dermapostasis, vaginitis, urinary tract infection, gingivitis and dental ulcer were lower and body temperature and duration of fever greatly improved in the supplementation than the placebo group. These data indicated that supplementation of micronutrients might increase immune function and reduce the incidence of common infections in type 2 diabetic outpatients.

Attrition from HIV Testing to Antiretroviral Therapy Initiation among Patients Newly Diagnosed with HIV in Haiti

PubMed Central

NOEL, Edva; ESPERANCE, Morgan; MCLAUGHLIN, Megan; BERTRAND, Rachel; DEVIEUX, Jessy; SEVERE, Patrice; MARCELIN, Abdias; NICOTERA, Janet; DELCHER, Chris; GRISWOLD, Mark; MEREDITH, Genevive; PAPE, Jean William; KOENIG, Serena P

2013-01-01

Objective We report rates and risk factors for attrition in the first cohort of patients followed through all stages from HIV testing to ART initiation. Design Cohort study of all patients diagnosed with HIV between January and June, 2009. Methods We calculated the proportion of patients who completed CD4 cell counts and initiated ART or remained in pre-ART care during two years of follow-up, and assessed predictors of attrition. Results Of 1,427 patients newly diagnosed with HIV, 680 (48%) either initiated ART or were retained in pre-ART care for the subsequent two years. One thousand eighty-three patients (76%) received a CD4 cell count and 973 (90%) returned for result; 297 (31%) had CD4 cell count < 200 cells/μl and of these, 256 (86%) initiated ART. Among 429 patients with CD4 > 350 cells/μl, 215 (50%) started ART or were retained in pre-ART care. Active TB was associated with lower odds of attrition prior to CD4 cell count (OR: 0.08; 95% CI: 0.03–0.25) but also higher odds of attrition prior to ART initiation (OR: 2.46; 95% CI: 1.29–4.71). Lower annual income (≤ $US125) was associated with higher odds of attrition prior to CD4 cell count (OR 1.65; 95% CI: 1.25–2.19), and prior to ART initiation among those with CD4 cell count > 350 cells/μl (OR: 1.74; 95% CI: 1.20–2.52). After tracking patients through a national database, the retention rate increased to only 57%. Conclusion Fewer than half of patients newly diagnosed with HIV initiate ART or remain in pre-ART care for two years in a clinic providing comprehensive services. Additional efforts to improve retention in pre-ART are critically needed. PMID:23254154

Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study.

PubMed

Rawson, T M; Dubb, S; Pozniak, A; Kelleher, W P; Mandalia, S; Gazzard, B; Barber, T J

2015-02-01

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18-50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Substance abuse treatment in an urban HIV clinic: who enrolls and what are the benefits?

PubMed

Pisu, Maria; Cloud, Gretchen; Austin, Shamly; Raper, James L; Stewart, Katharine E; Schumacher, Joseph E

2010-03-01

Substance abuse treatment (SAT) is important for HIV medical care. Characteristics of those who choose SAT and effects of SAT on HIV clinical outcomes are not understood. We compared patients who enrolled and did not enroll in a SAT program offered within an HIV clinic, and evaluated the effect of SAT on CD4 T-cell counts and HIV plasma viral load (VL). Subjects were assessed and invited to enroll in SAT. Enrollees chose to receive psychological and psychiatric treatment, or motivational enhancement and relapse prevention, or residential SAT. We used logistic regressions to determine factors associated with enrollment (age, race, sex, HIV transmission risk factors, CD4 T-cell counts, and VL at assessment). A two-period (assessment and six months after SAT) data analysis was used to analyze the effect of SAT on CD4 T-cell count and log VL controlling for changes in HIV therapy. We find that, compared to Decliners (N=76), Enrollees (N=78) were more likely to be females (29.5% vs. 6.6%, OR=5.32, 95% CI 1.61-17.6), and to report injection drug use (IDU) as the HIV transmission risk factor (23.1% vs. 9.2%, OR=3.92, CI 1.38-11.1). Age (37.2 vs. 38.4), CD4 T-cell count (377.3 vs. 409.2), and log VL (3.21 vs. 2.99) at assessment were similar across the two groups (p>0.05). After six months, Enrollees and Decliners' CD4 T-cell counts increased and log VL decreased. SAT did not affect the change in CD4 T-cell count (p=0.51) or log VL (p=0.73). Similar results were found for patients with CD4 T-cell count < or =350 at assessment. In this small sample of HIV-infected patients with a limited follow-up period, women were more likely to enroll in SAT than men, and SAT reached those who needed it, e.g., IDUs. We did not find an effect of SAT on HIV clinical outcomes.

Instability of delayed-type hypersensitivity skin test anergy in human immunodeficiency virus infection.

PubMed

Caiaffa, W T; Graham, N M; Galai, N; Rizzo, R T; Nelson, K E; Vlahov, D

1995-10-23

To evaluate stability of delayed-type hypersensitivity (DTH) skin test over time in human immunodeficiency virus (HIV)-seropositive and HIV-seronegative injecting drug users. A community-based cohort of injecting drug users who had serial skin testing with purified protein derivative tuberculin, mumps, and Candida albicans antigen. Delayed-type hypersensitivity anergy was defined as a skin test result of less than 3 mm for all three antigens; DTH positivity was a skin test result of 3 mm or greater for at least one antigen (Centers for Disease Control and Prevention, Atlanta, Ga, 1993). At baseline, 36% of HIV-seropositive subjects (n = 401) were anergic as compared with 14% of HIV-seronegative subjects (n = 552; P < .001). During follow-up, fewer HIV-seropositive subjects remained DTH positive (42%) and more remained anergic (19%) than of HIV-seronegative subjects (67% and 7%, respectively). Twenty-four percent of HIV-seropositive subjects who were initially DTH positive became anergic as compared with 15.3% of the HIV-seronegative subjects. However, the proportion changing from anergy to DTH positivity was greater among HIV-seropositive subjects (15%) than HIV-seronegative subjects (12%). In comparison to those who remained DTH positive, HIV-seropositive subjects with CD4 cell counts of less than 0.50 x 10(9)/L (odds ratio = 6.4) and less than 0.35 x 10(9)/L (odds ratio = 11.2) were more likely to remain anergic than those who had CD4 cell counts above 0.50 x 10(9)/L or were HIV seronegative. Although the prevalence and incidence of DTH anergy were higher in HIV-seropositive subjects, high rates of change in DTH status occurred in both directions. This suggests that instability of DTH skin testing is substantial and only partially dependent on HIV status. Although a single test may be an unreliable indicator of HIV-induced immunosuppression, two consecutive anergic readings were strongly associated with a CD4 cell count below 0.50 x 10(9)/L and particularly below 0.35 x 10(9)/L. For determining false negativity of tuberculin tests, persistent DTH anergy is more reliable than a single test among HIV-seropositive injecting drug users. Anergy testing appears to be unnecessary with CD4 cell counts greater than 0.5 x 10(9)/L.

Correlation between CD4 count and intensity of Candida colonization in the oropharynx of HIV-infected/ AIDS patient.

PubMed

Bandar, Ivo Novita Sah; Widodo, Djoko; Djauzi, Samsuridjal; Muthalib, Abdul; Soegondo, Sidartawan; Wahyuningsih, Retno

2006-01-01

To know the correlation between CD4 count and intensity of Candida colonizations in the oropharynx of HIV-infected/AIDS patients, to get the prevalence of oropharyngeal candidiasis (OPC), and to know what kind of Candida species that causes oropharynx candidiasis of HIV-infected/AIDS patients. A cross-sectional study was conducted in HIV-infected/AIDS patients who came as outpatients and inpatients in Cipto Mangunkusumo Hospital. The patients were interviewed, physically examined, their CD4 counts were checked, and their mouth rinse samples were taken to be cultured. Candida species was identified in CHROMagar media, and data were processed. From September 2004 until January 2005, 60 HIV-infected/AIDS patients were included in this study. There were 86.7% males and 13.3% females. Majority of the patients were from 20-30 years age group (85%). The most frequent transmission was among drug users (75%) followed by sexual contact (18.3%). The median of CD4 counts was 100 cells/il, ranged from 2 to 842 cells/il. Proportion of the OPC was 63.3% (CI 95% = 51.1 - 75.5). From 59 Candida isolates in this study, 74.58% were C. albicans. Candida non C. albicans species that were found in this trial were C. krusei, C. parapsilosis and C. tropicalis. There was significant correlation between low CD4 counts and high intensity of Candida colonization on the oropharynx of the subjects (r = -0.756). There was strong negative correlation (r = -0.756) between CD4 count and intensity of Candida colonization in the oropharynx of HIV-infected/AIDS patients. Proportion of OPC in this study was 63.3%. The most frequent species found in the oropharynx of the subjects was C. albicans.

Oral manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome and their correlation to cluster of differentiation lymphocyte count in population of North-East India in highly active antiretroviral therapy era.

PubMed

Nayak, Sarat Kumar; Das, Bijay Kumar; Das, Surya Narayan; Mohapatra, Namita; Nayak, Suryakanti; Bhuyan, Lipsa

2016-01-01

The human immunodeficiency virus (HIV) infection which manifests as acquired immunodeficiency syndrome (AIDS) is a disease involving the defects of the T-lymphocyte arm of the immune system. Certain laboratory parameters such as the cluster of differentiation (CD4) count and clinical parameters have long been used as markers of disease progression. In industrialized countries, many studies show a highly correlation between the incidence of oral lesions and immunosuppression and hence, can be used as a marker of immunosuppression. This might not be applicable to a developing country like India. In this study, efforts have been made to supplement the present knowledge on various aspects of oral manifestations in HIV patients in the Indian subcontinent. To correlate the oral manifestations in HIV/AIDS patients to the level of circulating CD4+ T-lymphocyte count and their effect in anti-retroviral therapy (ART). A total of 104 HIV positive patients were examined for oral lesions. The CD4 count estimated on the same day by fluorescent activated cell sort count machine was then correlated with various oral lesions. Oral manifestations appeared when CD4 count decreased below 500 cells/mm 3 . Moreover, oral lesions found at different stages showed very strong correlation to their respective CD4 count. Furthermore, there was considerable decline in the incidence of oral manifestations in patients undergoing highly active ART. Oral manifestations are highly predictive markers of severe immune deterioration and disease progression in HIV patients.

Risk factors for increased immune reconstitution in response to Mycobacterium tuberculosis antigens in tuberculosis HIV-infected, antiretroviral-naïve patients.

PubMed

da Silva, Tatiana Pereira; Giacoia-Gripp, Carmem Beatriz Wagner; Schmaltz, Carolina A; Sant'Anna, Flavia Marinho; Saad, Maria Helena; Matos, Juliana Arruda de; de Lima E Silva, Julio Castro Alves; Rolla, Valeria Cavalcanti; Morgado, Mariza Gonçalves

2017-09-06

Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution. This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-γ upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits. Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-γ production in response to PPD antigen were CD4 + T cell counts <200 cells/mm 3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4 + T cell counts. Moreover, the factors associated with the production of IFN-γ in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4 + T cell counts at follow-up visits of ≥200 cells/mm 3 . These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-γ production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.

HIV sequence diversity during the early phase of infection is associated with HIV DNA reductions during antiretroviral therapy.

PubMed

Wang, Nidan; Li, Yijia; Han, Yang; Xie, Jing; Li, Taisheng

2017-06-01

The association between baseline human immunodeficiency virus (HIV) sequence diversity and HIV DNA decay after the initiation of antiretroviral therapy (ART) remains uncharacterized during the early stages of HIV infection. Samples were obtained from a cohort of 17 patients with early HIV infection (<6 months after infection) who initiated ART, and the C2V5 region of the HIV-1 envelope (env) gene was amplified via single genome amplification (SGA) to determine the peripheral plasma HIV quasispecies. We categorized HIV quasispecies into two groups according to baseline viral sequence genetic distance, which was determined by the Poisson-Fitter tool. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), viral load, and T cell subsets were measured prior to and after the initiation of ART. The median SGA sequence number was 17 (range 6-28). At baseline, we identified 7 patients with homogeneous viral populations (designated the Homogeneous group) and 10 patients with heterogeneous viral populations (designated the Heterogeneous group) based on SGA sequences. Both groups exhibited similar HIV DNA decay rates during the first 6 months of ART (P > 0.99), but the Homogenous group experienced more prominent decay than the Heterogeneous group after 6 months (P = 0.037). The Heterogeneous group had higher CD4 cell counts after ART initiation; however, both groups had comparable recovery in terms of CD4/CD8 ratios and CD8 T cell activation levels. Viral population homogeneity upon the initiation of ART is associated with a decrease in HIV DNA levels during ART. J. Med. Virol. 89:982-988, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Trends in CD4 cell count response to first-line antiretroviral treatment in HIV-positive patients from Asia, 2003-2013: TREAT Asia HIV Observational Database Low Intensity Transfer.

PubMed

De La Mata, Nicole L; Ly, Penh S; Ng, Oon T; Nguyen, Kinh V; Merati, Tuti P; Pham, Thuy T; Lee, Man P; Choi, Jun Y; Sohn, Annette H; Law, Matthew G; Kumarasamy, Nagalingeswaran

2017-11-01

Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006-9 and 2010-13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003-5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003-5 to 173 cells/µl in 2010-13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers.

Trends in CD4 Count Testing, Retention in Pre-ART Care, and ART Initiation Rates over the First Decade of Expansion of HIV Services in Haiti

PubMed Central

Koenig, Serena P.; Bernard, Daphne; Dévieux, Jessy G.; Atwood, Sidney; McNairy, Margaret L.; Severe, Patrice; Marcelin, Adias; Julma, Pierrot; Apollon, Alexandra; Pape, Jean W.

2016-01-01

Background High attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is widely reported. Though treatment guidelines have changed to broaden ART eligibility and services have been widely expanded over the past decade, data on the temporal trends in pre-ART outcomes are limited; such data would be useful to guide future policy decisions. Methods We evaluated temporal trends and predictors of retention for each step from HIV testing to ART initiation over the past decade at the GHESKIO clinic in Port-au-Prince Haiti. The 24,925 patients >17 years of age who received a positive HIV test at GHESKIO from March 1, 2003 to February 28, 2013 were included. Patients were followed until they remained in pre-ART care for one year or initiated ART. Results 24,925 patients (61% female, median age 35 years) were included, and 15,008 (60%) had blood drawn for CD4 count within 12 months of HIV testing; the trend increased over time from 36% in Year 1 to 78% in Year 10 (p<0.0001). Excluding transfers, the proportion of patients who were retained in pre-ART care or initiated ART within the first year after HIV testing was 84%, 82%, 64%, and 64%, for CD4 count strata ≤200, 201 to 350, 351 to 500, and >500 cells/mm3, respectively. The trend increased over time for each CD4 strata, and in Year 10, 94%, 95%, 79%, and 74% were retained in pre-ART care or initiated ART for each CD4 strata. Predictors of pre-ART attrition included male gender, low income, and low educational status. Older age and tuberculosis (TB) at HIV testing were associated with retention in care. Conclusions The proportion of patients completing assessments for ART eligibility, remaining in pre-ART care, and initiating ART have increased over the last decade across all CD4 count strata, particularly among patients with CD4 count ≤350 cells/mm3. However, additional retention efforts are needed for patients with higher CD4 counts. PMID:26901795

Poverty, hunger, education, and residential status impact survival in HIV.

PubMed

McMahon, James; Wanke, Christine; Terrin, Norma; Skinner, Sally; Knox, Tamsin

2011-10-01

Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.

Factors influencing utilization of postpartum CD4 count testing by HIV-positive women not yet eligible for antiretroviral treatment.

PubMed

Gilles, Kate P; Zimba, Chifundo; Mofolo, Innocent; Bobrow, Emily; Hamela, Gloria; Martinson, Francis; Hoffman, Irving; Hosseinipour, Mina

2011-03-01

Delayed antiretroviral initiation is associated with increased mortality, but individuals frequently delay seeking treatment. To increase early antiretroviral therapy (ART) enrollment of HIV-positive women, antenatal clinics are implementing regular, postpartum CD4 count testing. We examined factors influencing women's utilization of extended CD4 count testing. About 53 in-depth interviews were conducted with nurses, patients, social support persons, and government health officials at three antenatal clinics in Lilongwe, Malawi. Counseling and positive interactions with staff emerged as facilitating factors. Women wanted to know their CD4 count, but didn't understand the importance of early ART initiation. Support from husbands facilitated women's return to the clinic. Reminders were perceived as helpful but ineffectively employed. Staff identified lack of communication, difficulty in tracking, and referring women as barriers. Counseling messages should emphasize the importance of starting ART early. Clinics should focus on male partner involvement, case management, staff communication, and appointment reminders. Follow-up should be offered at multiple service points.

Single-cell analysis of lymphokine imbalance in asymptomatic HIV-1 infection: evidence for a major alteration within the CD8+ T cell subset

PubMed Central

Sousa, A E; Victorino, R M M

1998-01-01

In this study we investigated at single-cell level by flow cytometry the potential of T cell cytokine production in asymptomatic HIV-1-infected subjects with > 200 CD4 counts and possible correlation with T helper cell depletion and viral load. Mitogen-stimulated peripheral blood mononuclear cells from 32 HIV-1+ patients and 16 healthy subjects were intracytoplasmically stained for IL-2, interferon-gamma (IFN-γ), IL-4 or IL-10, and the frequency of cytokine-producing cells was assessed in total T cells, CD4, CD8 and CD45RO subsets as well as in CD69+CD3+ gated lymphocytes. HIV-1+ patients, irrespective of their degree of CD4 depletion, exhibited a major increase in IFN-γ+ CD8 T cells, largely due to CD28− cells, as well as a decrease in the capacity of CD8 T cells to produce IL-2. Patients with > 500 CD4 counts showed a diminished frequency of IL-4 expression in CD4 T cells and a negative correlation was found between this parameter and the ex vivo CD4 counts in the 32 patients. Analysis of patients stratified according to viral load revealed a significantly higher proportion of IL-2-producing CD4 cells in the group with < 5000 RNA copies/ml. In short, using single-cell analysis and an antigen-presenting cell-independent stimulus, we have not been able to find any significant cytokine imbalances in the CD4 subset, suggesting that the well described T helper defects are not due to intrinsic alterations in the potential of CD4 T cells to produce cytokines. On the other hand, the major disturbances in the CD8 T lymphocytes agree with the marked activation and possible replicative senescence of CD8 T cells and emphasize the role of this subset in HIV immunopathogenesis. PMID:9649194

Delayed effects of rhG-CSF mobilization treatment and apheresis on circulating CD34+ and CD34+ Thy-1dim CD38- progenitor cells, and lymphoid subsets in normal stem cell donors for allogeneic transplantation.

PubMed

Körbling, M; Anderlini, P; Durett, A; Maadani, F; Bojko, P; Seong, D; Giralt, S; Khouri, I; Andersson, B; Mehra, R; vanBesien, K; Mirza, N; Przepiorka, D; Champlin, R

1996-12-01

Allogeneic transplantation of peripheral blood progenitor cells (PBPC) is emerging as a new stem cell transplant modality. Rather than undergoing general anesthesia for bone marrow harvest, normal blood stem cell donors are subjected to rhG-CSF mobilization treatment followed by single or multiple apheresis. Whereas the effects of cytokine treatment and apheresis on stem cell peripheralization and collection have been described, little is known about delayed effects of rhG-CSF treatment and apheresis on a normal hematopoietic system, and there are no long-term data that address safety issues. Ten normal, patient-related donors underwent a 3 or 4 day rhG-CSF (filgrastim) treatment (12 micrograms/kg/day) followed by single or tandem apheresis. We monitored peripheral blood (PB) cellularity including CD34+ and lymphoid subsets at baseline, during cytokine treatment, prior to apheresis, and at days 2, 4, 7, 30 and 100 post-apheresis. The PB progenitor cell concentration peak prior to apheresis was followed by a nadir by day 7 and normalized by day 30, with the exception of the most primitive CD34+ Thy-1dim CD38- progenitor subset that reached a nadir by day 30. Lymphoid subsets such as CD3, 4, 8, suppressor cells (CD3+ 4- 8- TCR+ alpha beta), and B cells (CD19+) showed a similar pattern with a nadir concentration by day 7, followed, except for B cells, by a rebound by day 30 and subnormal counts at day 100. The PB concentrations of hemoglobin and platelets dropped mainly due to the apheresis procedure itself, and normalized by day 30. With cytokine treatment, the PB alkaline phosphatase and lactate dehydrogenase concentrations increased 2.2- and 2.8-fold, respectively, over baseline, and returned to normal range by day 30. Based on the preliminary nature of this study, the clinical relevance of these findings is still unclear.

Population Pharmacokinetics and Pharmacodynamic Modeling of Abacavir (1592U89) from a Dose-Ranging, Double-Blind, Randomized Monotherapy Trial with Human Immunodeficiency Virus-Infected Subjects

PubMed Central

Weller, Stephen; Radomski, Kristine M.; Lou, Yu; Stein, Daniel S.

2000-01-01

Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4+ cell counts of ≥100/mm3 and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (Cmax) and the area under the concentration-time curve from time zero to infinity (AUC0–∞) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC0–∞. A significant correlation was observed between Cmax and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log10 time-averaged AUC0–∞ minus baseline (AAUCMB) values for HIV-1 RNA and CD4+ cell count correlated significantly with Cmax and AUC0–∞, but with better model fits for AUC0–∞. The increase in AAUCMB values for CD4+ cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log10 difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC0–∞ from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing. PMID:10898675

Virologic and Immunologic Outcomes in HIV-Infected Patients with Cancer.

PubMed

Riedel, David J; Stafford, Kristen A; Vadlamani, Aparna; Redfield, Robert R

2017-05-01

Achievement and maintenance of virologic suppression after cancer diagnosis have been associated with improved outcomes in HIV-infected patients, but few studies have analyzed the virologic and immunologic outcomes after a cancer diagnosis. All HIV-infected patients with a diagnosis of cancer between 2000 and 2011 in an urban clinic population in Baltimore, MD, were included for review. HIV-related outcomes (HIV-1 RNA viral load and CD4 cell count) were abstracted and compared for patients with non-AIDS-defining cancers (NADCs) and AIDS-defining cancers (ADCs). Four hundred twelve patients with baseline CD4 or HIV-1 RNA viral load data were analyzed. There were 122 (30%) diagnoses of ADCs and 290 (70%) NADCs. Patients with NADCs had a higher median age (54 years vs. 43 years, p < .0001) and a higher frequency of hepatitis C coinfection (52% vs. 36%, p = .002). The median baseline CD4 was lower for patients with ADCs (137 cells/mm 3 vs. 314 cells/mm 3 ) and patients with NADCs were more likely to be suppressed at cancer diagnosis (59% vs. 25%) (both p < .0001). The median CD4 for patients with NADCs was significantly higher than patients with ADCs at 6 and 12 months after diagnosis and higher at 18 and 24 months, but not significantly. Patients with an NADC had 2.19 times (95% CI 1.04-4.62) the adjusted odds of being suppressed at 12 months and 2.17 times the odds (95% CI 0.92-5.16) at 24 months compared to patients with an ADC diagnosis. For patients diagnosed with ADCs and NADCs in this urban clinic setting, both virologic suppression and immunologic recovery improved over time. Patients with NADCs had the highest odds of virologic suppression in the 2 years following cancer diagnosis.

Risk factors for CMV retinitis among individuals with HIV and low CD4 count in northern Thailand: importance of access to healthcare.

PubMed

Leenasirimakul, Prattana; Liu, Yingna; Jirawison, Choeng; Khienprasit, Nitta; Kamphaengkham, Siripim; Ausayakhun, Somsanguan; Chen, Jenny; Yen, Michael; Heiden, David; Holland, Gary N; Margolis, Todd P; Keenan, Jeremy D

2016-08-01

To determine if poor access to healthcare is associated with increased cytomegalovirus (CMV) retinitis risk among patients with HIV with CD4 counts of <100 cells/μL screened in a resource-limited setting. This is a prospective cross-sectional study. Patients with known HIV and a CD4 count of <100 cells/μL attending an HIV clinic in Chiang Mai, Thailand, completed a standardised questionnaire and underwent dilated fundus examination. Participants without CMV retinitis were invited for repeated examinations every 3 months until their CD4 count exceeded 100 cells/μL. The relationship between various potential risk factors and CMV retinitis was assessed with logistic regression. 103 study participants were enrolled. At enrolment, the mean age was 37.5 (95% CI 35.7 to 39.2) years, 61.2% (95% CI 51.6% to 70.7%) were male and the mean CD4 count was 29.5 (95% CI 25.9 to 33.1) cells/μL. 21 eyes from 16 (15.5%) participants were diagnosed with CMV retinitis. In multivariate analyses, CMV retinitis was significantly associated with lower CD4 count (OR 1.42 per 10-cell decrement, 95%CI 1.05 to 1.93), longer travel time to clinic (OR 3.85 for those with >30-min travel time, 95% CI 1.08 to 13.8) and lower income (OR 1.22 per US$50 less income, 95% CI 1.02 to 1.47). CD4 count, low income and longer travel time to clinic were significant risk factors for CMV retinitis among patients with HIV in a resource-limited setting. These results suggest that reducing blindness from CMV retinitis should focus on increasing accessibility of screening examinations to poor and hard-to-reach patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Long-Term Effects of Highly Active Antiretroviral Therapy on CD4+ Cell Evolution among Children and Adolescents Infected with HIV: 5 Years and Counting

PubMed Central

Patel, Kunjal; Hernán, Miguel A.; Williams, Paige L.; Seeger, John D.; McIntosh, Kenneth; Van Dyke, Russell B.; Seage, George R.

2011-01-01

Background Lower percentages of CD4+ T lymphocytes are associated with adverse clinical outcomes among children and adolescents infected with human immunodeficiency virus (HIV). CD4+ lymphocyte percentage generally increases with receipt of highly active antiretroviral therapy (HAART), but long-term follow-up is required to assess whether these increases in CD4+ cell percentage are maintained and whether they lead to normal CD4+ cell percentages in children with severe immunosuppression. Methods The study population included 1236 children and adolescents perinatally infected with HIV who were enrolled in a US-based multicenter prospective cohort study (Pediatric AIDS Clinical Trials Group 219/219C) and who were not receiving HAART at study initiation. We estimated the effects of HAART, HAART with protease inhibitors, and HAART with nonnucleoside reverse-transcriptase inhibitors on CD4+ cell percentage, using marginal structural models to account for confounding by severity. Results Initiation of any type of HAART increased CD4+ cell percentage by 2.34% (95% confidence interval, 1.35%–3.33%) in the first year, relative to noninitiation of HAART. The substantial increases in CD4+ cell percentage observed after the first year of experience with these combination therapies were followed by relatively smaller increases that continued for 5 years after initiation. Although larger increases in CD4+ cell percentage were observed among children with a greater degree of immunosuppression at baseline, the mean CD4+ cell percentage after 5 years of HAART did not reach normal levels. Conclusions Our study supports the initiation of HAART in children before severe immunosuppression occurs for long-term maintenance of normal CD4+ cell percentages. This beneficial result must be weighed against the evidence of potential adverse events associated with the prolonged use of such therapy. PMID:18426371

Comparative Analysis of Gender Differences in the HIV-1 Infection Dynamics

NASA Astrophysics Data System (ADS)

Ballesteros, P.; Estrada, J. L.; Barriga, G.; Molinar, F.; Hernández, M. C.; Huerta, L.; Cocho, G.; Villarreal, C.

2006-09-01

We have performed a retrospective study of the HIV-1 viral load and CD4 T-cell counts in blood plasma of more than 3000 Mexican patients. We found that women had consistently lower viral loads than men for CD4 T-cell counts higher than 50 cells/μL and higher viral loads when CD4 T-cell counts were at most 50 cells/μL. Our results show the same pattern as the one reported in studies performed in European and North American populations. We present theoretical predictions of viral load dynamics during highly active antiretroviral therapy taking into account gender differences.

Implementation and Operational Research: CD4 Count Monitoring Frequency and Risk of CD4 Count Dropping Below 200 Cells Per Cubic Millimeter Among Stable HIV-Infected Patients in New York City, 2007-2013.

PubMed

Myers, Julie E; Xia, Qiang; Torian, Lucia V; Irvine, Mary; Harriman, Graham; Sepkowitz, Kent A; Shepard, Colin W

2016-03-01

The evidence has begun to mount for diminishing the frequency of CD4 count testing. To determine whether these observations were applicable to an urban US population, we used New York City (NYC) surveillance data to explore CD4 testing among stable patients in NYC, 2007-2013. We constructed a population-based retrospective open cohort analysis of NYC HIV surveillance data. HIV+ patients aged ≥ 13 years with stable viral suppression (≥ 1 viral load the previous year; all <400 copies per milliliter) and immune status (≥ 1 CD4 the previous year; all ≥ 200 cells per cubic millimeter) entered the cohort the following year beginning January 1, 2007. Each subsequent year, eligible patients not previously included entered the cohort on January 1. Outcomes were annual frequency of CD4 monitoring and probability of maintaining CD4 ≥ 200 cells per cubic millimeter. A multivariable Cox model identified factors associated with maintaining CD4 ≥ 200 cells per cubic millimeter. During 1.9 years of observation (median), 62,039 patients entered the cohort. The mean annual number of CD4 measurements among stable patients was 2.8 and varied little by year or characteristic. Two years after entering, 93.4% and 97.8% of those with initial CD4 350-499 and CD4 ≥ 500 cells per cubic millimeter, respectively, maintained CD4 ≥ 200 cells per cubic millimeter. Compared to those with initial CD4 ≥ 500 cells per cubic millimeter, those with CD4 200-349 cells per cubic millimeter and CD4 350-499 cells per cubic millimeter were more likely to have a CD4 <200 cells per cubic millimeter, controlling for sex, race, age, HIV risk group, and diagnosis year. In a population-based US cohort with well-controlled HIV, the probability of maintaining CD4 ≥ 200 cells per cubic millimeter for ≥ 2 years was >90% among those with initial CD4 ≥ 350 cells per cubic millimeter, suggesting that limited CD4 monitoring in these patients is appropriate.

Airway Inflammation and Illness Severity in Response to Experimental Rhinovirus Infection in Asthma

PubMed Central

Zhu, Jie; Message, Simon D.; Qiu, Yusheng; Mallia, Patrick; Kebadze, Tatiana; Contoli, Marco; Ward, Christine K.; Barnathan, Elliot S.; Mascelli, Mary Ann; Kon, Onn M.; Papi, Alberto; Stanciu, Luminita A.; Jeffery, Peter K.

2014-01-01

Background: The nature of bronchial mucosal inflammation and its physiologic and clinical significance in rhinovirus-induced asthma exacerbations is unclear. We investigated bronchial mucosal inflammatory response and its association with physiologic and clinical outcomes in an experimental model of rhinovirus-induced asthma exacerbations. Methods: We used immunohistochemistry methods to detect phenotypes of inflammatory cells infiltrating the bronchial mucosa before and after experimental rhinovirus infection in 10 subjects with asthma and 15 normal subjects. Results: Compared with baseline, rhinovirus infection significantly increased the number of epithelial (P = .005) and subepithelial (P = .017) neutrophils in subjects with asthma only and subepithelial CD68+ macrophages in both subjects with asthma (P = .009) and normal subjects (P = .018) but more so in those with asthma (P = .021). Numbers of CD45+, CD68+, and CD20+ cells; neutrophils; and eosinophils at day 4 postinfection were positively associated with virus load (r = 0.50-0.72, P = .016-0.03). At acute infection in subjects with asthma, CD4+ cells correlated with chest symptom scores (r = 0.69, P = .029), the fall in the 10% fall in FEV1 (PC10) correlated with neutrophils (r = −0.89, P = .029), the PC10 correlated inversely with CD4+ (r = −0.67, P = .023) and CD8+ cells (r = −0.65, P = .03), the 20% fall in FEV1 was inversely associated with CD20+ cells (r = −0.65, P = .03), and higher epithelial CD8+ cell counts were significantly associated with a greater maximum fall in FEV1 (r = −0.72, P = .03), whereas higher subepithelial mast cell counts were significantly associated with a lower maximum percent fall in peak expiratory flow (r = 0.8, P = .024). Conclusions: In subjects with asthma, rhinovirus infection induces bronchial mucosal neutrophilia and more severe monocyte/macrophage infiltration than in normal subjects. Airway neutrophils, eosinophils, and T and B lymphocytes during infection are related to virus load and physiologic and clinical severity, whereas mast cells are related to greater lung function. PMID:24457412

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

PubMed Central

Benjamin, Ronald; Banerjee, Atoshi; Sunder, Sharada Ramaseri; Gaddam, Sumanlatha; Valluri, Vijaya Lakshmi; Banerjee, Sharmistha

2013-01-01

Background Cytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy. Methodology/Principal Findings We analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio. Conclusion/Significance With these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse. PMID:23936398

Serum Adenosine Deaminase (ADA) Activity: A Novel Screening Test to Differentiate HIV Monoinfection From HIV-HBV and HIV-HCV Coinfections.

PubMed

Abdi, Mohammad; Rahbari, Rizgar; Khatooni, Zahed; Naseri, Nima; Najafi, Adel; Khodadadi, Iraj

2016-05-01

CD4(+) cell count, the common HIV infection screening test, is costly and unable to differentiate HIV monoinfection from its concurrent infection with hepatitis B or C virus. We aimed to ascertain diagnostic value of serum adenosine deaminase (ADA) activity as a useful tool to differentiate HIV mono- and co-infection. Blood samples were collected from 30 HIV-HBV and 30 HIV-HCV coinfected patients, 33 HIV positive subjects, and 72 controls. CD4(+) cell count, serum total ADA (tADA), and ADA1, and ADA2 isoenzyme activities were determined and their sensitivity and specificity were computed. tADA and ADA2 activities were significantly higher and CD4(+) counts were markedly lower in all patients compared with controls. Strong inverse agreements between CD4(+) cell counts and both tADA and ADA2 activities were observed. Serum tADA and ADA1 activities showed the highest specificity and the highest sensitivity, respectively, for differentiating HIV monoinfection from HIV-HBV and HIV-HCV coinfections. We showed strong agreement and correlation between CD4(+) cell count and ADA enzyme activity. Based on high ADA sensitivity and specificity, it is concluded that determination of ADA activity might be a novel diagnostic tool to distinguish of HIV monoinfection from its coinfection with HBV or HCV. © 2015 Wiley Periodicals, Inc.

Pneumocystis jirovecii colonisation in HIV-positive and HIV-negative subjects in Cameroon.

PubMed

Riebold, D; Enoh, D O; Kinge, T N; Akam, W; Bumah, M K; Russow, K; Klammt, S; Loebermann, M; Fritzsche, C; Eyong, J E; Eppel, G; Kundt, G; Hemmer, C J; Reisinger, E C

2014-06-01

To determine the prevalence of Pneumocystis pneumonia (PCP), a major opportunistic infection in AIDS patients in Europe and the USA, in Cameroon. Induced sputum samples from 237 patients without pulmonary symptoms (126 HIV-positive and 111 HIV-negative outpatients) treated at a regional hospital in Cameroon were examined for the prevalence of Pneumocystis jirovecii by specific nested polymerase chain reaction (nPCR) and staining methods. CD 4 counts and the history of antiretroviral therapy of the subjects were obtained through the ESOPE database system. Seventy-five of 237 study participants (31.6%) were colonised with Pneumocystis, but none showed active PCP. The Pneumocystis colonisation rate in HIV-positive subjects was more than double that of HIV-negative subjects (42.9% vs. 18.9%, P < 0.001). In the HIV-positive group, the colonisation rate corresponds to the reduction in the CD 4 lymphocyte counts. Subjects with CD 4 counts >500 cells/μl were colonised at a rate of 20.0%, subjects with CD 4 counts between 200 and 500 cells/μl of 42.5%, and subjects with CD 4 counts <200 cells/μl of 57.1%. Colonisation with Pneumocystis in Cameroon seems to be comparable to rates found in Western Europe. Prophylactic and therapeutic measures against Pneumocystis should be taken into account in HIV care in western Africa. © 2014 John Wiley & Sons Ltd.

Secondary syphilis in HIV positive individuals: correlation with histopathologic findings, CD4 counts, and quantity of treponemes in microscopic sections.

PubMed

Rosa, Gabriela; Procop, Gary W; Schold, Jesse D; Piliang, Melissa P

2016-10-01

Although syphilis is uncommon, infection rates are much higher in HIV-infected individuals than the general population. A proposed explanation is impaired cellular immunity with HIV infection. A search of one institution yielded 10 patients with a diagnosis of secondary syphilis on skin biopsy, positive syphilis serology and available CD4 counts. We evaluated 11 biopsies from the 10 patients. We correlated the patients' CD4 counts with the histologic findings and with the number of treponemes on skin biopsies, highlighted by immunohistochemistry (IHC). We also compared the detection of spirochetes in silver stained sections (e.g. Warthin-Starry) with T. pallidum IHC. All biopsies were assessed for various histologic features. The sensitivity of IHC to detect treponemes was 64% and of silver stain was 9% (p-value 0.04). The number of treponemes on the biopsies was determined by IHC. High numbers of spirochetes (i.e. >100 per 10 hpf) were only seen in patients with CD4 counts less than 250 cells/ml. The most consistent histologic finding was a moderate to severe lymphoplasmacytic infiltrate. Although the study is small, it appears that a higher number of spirochetes is associated with CD4 counts less than 250 cell/ml. The T. pallidum IHC stain was vastly superior to the Warthin-Starry stain. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women.

PubMed

Cohen, R A; Boland, R; Paul, R; Tashima, K T; Schoenbaum, E E; Celentano, D D; Schuman, P; Smith, D K; Carpenter, C C

2001-02-16

To determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. A semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a woman's CD4 cell count fell to < 100 x 10(6) cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. HAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 +/- 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. HAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.

CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study.

PubMed

Wittkop, Linda; Arsandaux, Julie; Trevino, Ana; Schim van der Loeff, Maarten; Anderson, Jane; van Sighem, Ard; Böni, Jürg; Brun-Vezinet, Françoise; Soriano, Vicente; Boufassa, Faroudy; Brockmeyer, Norbert; Calmy, Alexandra; Dabis, François; Jarrin, Inma; Dorrucci, Maria; Duque, Vitor; Fätkenheuer, Gerd; Zangerle, Robert; Ferrer, Elena; Porter, Kholoud; Judd, Ali; Sipsas, Nikolaos V; Lambotte, Olivier; Shepherd, Leah; Leport, Catherine; Morrison, Charles; Mussini, Cristina; Obel, Niels; Ruelle, Jean; Schwarze-Zander, Carolyne; Sonnerborg, Anders; Teira, Ramon; Torti, Carlo; Valadas, Emilia; Colin, Celine; Friis-Møller, Nina; Costagliola, Dominique; Thiebaut, Rodolphe; Chene, Geneviève; Matheron, Sophie

2017-10-01

CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A randomized controlled trial on the efficacy of resistant dextrin, as functional food, in women with type 2 diabetes: Targeting the hypothalamic-pituitary-adrenal axis and immune system.

PubMed

Farhangi, Mahdieh Abbasalizad; Javid, Ahmad Zare; Sarmadi, Bahareh; Karimi, Poran; Dehghan, Parvin

2018-08-01

The aim of this trial was to determine the efficacy of a resistant dextrin on immune-mediated inflammation and hypothalamic-pituitary-adrenal axis in women with type 2 diabetes mellitus (T2DM). Females (n = 55) with T2DM were randomly allocated into intervention group (n = 30) and control group (n = 25), in which they received 10 g/d of Nutriose ® 06 (a resistant dextrin) or maltodextrin for 8 weeks, respectively. Fasting blood samples were taken to measure immune system related parameters like white blood cell count, CD4, CD8, interferon-γ (IFNγ), interleukins (IL12, IL4, IL10), cortisol, tryptophan (TRP), ACTH (Adrenocorticotropic hormone), Kynurenine (KYN) and plasma lipopolysaccharide (LPS) at the beginning and end of trial. Mental health was assessed using general health questionnaire (GHQ) and depression, anxiety and stress scale (DASS). Resistant dextrin caused a significant decrease in levels of cortisol, KYN, KYN/TRP ratio, IFNγ, IL12, IFNγ/IL10 ratio, LPS, and a significant increase in the monocyte, GHQ, DASS, CD8, IL10, IL4 in the intervention group as compared with baseline. A significant decrease in the level of LPS (-6.20 EU/mL, -17.8%), IFNγ (-0.6 pg/ml, -26.8%), cortisol (-2.6 μg/dl, -20.9%), IFNγ/IL10 ratio (0.01, 10%), GHQ (-5.1, -12.5%), DASS (-10.4, -38.4%), KYN/TRP ratio (6.8, 29.1%), and a significant increase in levels of CD8 (6.4%, 6.1%) and IL10 (2.6 pg/ml, 21.6%) in the intervention group as compared with the control group (P < 0.05). No significant changes were observed in white blood cell count, CD4, CD4/CD8 ratio, ACTH, KYN, TRP, IL4 and IL12 in the intervention group as compared with the control group (P > 0.05). Supplementation of Nutriose ® 06 may have beneficial effects on mental health and the immune system response in women with T2DM. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Prevalence and Evolution of Renal Impairment in People Living With HIV in Rural Tanzania.

PubMed

Mapesi, Herry; Kalinjuma, Aneth V; Ngerecha, Alphonce; Franzeck, Fabian; Hatz, Christoph; Tanner, Marcel; Mayr, Michael; Furrer, Hansjakob; Battegay, Manuel; Letang, Emilio; Weisser, Maja; Glass, Tracy R

2018-04-01

We assessed the prevalence, incidence, and predictors of renal impairment among people living with HIV (PLWHIV) in rural Tanzania. In a cohort of PLWHIV aged ≥15 years enrolled from January 2013 to June 2016, we assessed the association between renal impairment (estimated glomerural filtration rate < 90 mL/min/1.73 m 2 ) at enrollment and during follow-up with demographic and clinical characteristcis using logistic regression and Cox proportional hazards models. Of 1093 PLWHIV, 172 (15.7%) had renal impairment at enrollment. Of 921 patients with normal renal function at baseline, 117 (12.7%) developed renal impairment during a median follow-up (interquartile range) of 6.2 (0.4-14.7) months. The incidence of renal impairment was 110 cases per 1000 person-years (95% confidence interval [CI], 92-132). At enrollment, logistic regression identified older age (adjusted odds ratio [aOR], 1.79; 95% CI, 1.52-2.11), hypertension (aOR, 1.84; 95% CI, 1.08-3.15), CD4 count <200 cells/mm 3 (aOR, 1.80; 95% CI, 1.23-2.65), and World Health Organization (WHO) stage III/IV (aOR, 3.00; 95% CI, 1.96-4.58) as risk factors for renal impairment. Cox regression model confirmed older age (adjusted hazard ratio [aHR], 1.85; 95% CI, 1.56-2.20) and CD4 count <200 cells/mm 3 (aHR, 2.05; 95% CI, 1.36-3.09) to be associated with the development of renal impairment. Our study found a low prevalence of renal impairment among PLWHIV despite high usage of tenofovir and its association with age, hypertension, low CD4 count, and advanced WHO stage. These important and reassuring safety data stress the significance of noncommunicable disease surveillance in aging HIV populations in sub-Saharan Africa.

Raltegravir plus abacavir/lamivudine in virologically suppressed HIV-1-infected patients: 48-week results of the KIRAL study.

PubMed

Troya, Jesús; Montejano, Rocio; Ryan, Pablo; Gómez, Cristina; Matarranz, Mariano; Cabello, Alfonso; Vera, Francisco; Sepúlveda, María Antonia; Santos, Ignacio; Samperiz, Gloria; Bachiller, Pablo; Boix, Vicente; Barrufet, Pilar; Cervero, Miguel; Sanz, José; Solís, Javier; Yllescas, María; Valencia, Eulalia

2018-01-01

Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy. The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9-24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks. Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.

New mononuclear leukocyte-like populations within the granulocyte scatter gate detected by flow cytometry (Conference Presentation)

NASA Astrophysics Data System (ADS)

Melzer, Susanne; Löffler, Markus; Kautzner, Marlene; Tárnok, Attila

2017-02-01

Granulocytes are the major players in innate immunity and are prognostic markers in diseases. An in-depth phenotypic characterization of granulocyte subtypes and correlation with biometry or lifestyle is so far lacking. The reason is, that either preparation of mononuclear cells was analyzed or that cells in the neutrophil window were neglected in the analysis. Here we show for the first time lymphocyte- (LL) and monocyte-like (ML) cells within the granulocyte scatter gate as new, previously unknown cell subpopulation. Immunophenotyping of 905 healthy German adults from the LIFE study [1] was performed by 10-color flow cytometry [2]. Age of men (n=420): 56.5±14.0 years, women (n=485): 56.7±13.6 y (range of 18-81 y). Data analyzed by FlowJo v10.0.6. Values compared by Mann-Whitney-U test: men vs women, young (18-49 y) vs. elderly (50-81 y.) men, and young (19-49 y.) vs. elderly (50-81 y.) women; significance: p<0.05. Within the granulocyte gate four phenotypically distinct cell types were detected (all CD45+, SSCmid-high): LL1 CD3+,CD4+,CD8++,CD16/56+,CD38+,HLA-DR+ LL2 CD3+,CD4low,CD8+,CD38low LL3 CD3+,CD4+,CD8- ML1 CD3-,CD4low,CD14+,CD38+ LL2 counts were increased in men (p=0.042), as well as ML1 counts (p <0.001). Most of the cell counts were not dependent on age, except LL2 in women. In conclusion, new lymphocyte like cell types with the neutrophil scatter characteristics are reported. Counts correlate with age and gender. We plan to sort these new subtypes for further functional characterization and aim to establish them as cellular biomarkers for the early detection of various diseases. [1] BMC Public Health. 2015;15:691; [2] Cytometry A. 2014;85(9):781

Adoption of the chronic care model to improve HIV care

PubMed Central

Tu, David; Belda, Patricia; Littlejohn, Doreen; Pedersen, Jeanette Somlak; Valle-Rivera, Juan; Tyndall, Mark

2013-01-01

Abstract Objective To measure the effectiveness of implementing the chronic care model (CCM) in improving HIV clinical outcomes. Design Multisite, prospective, interventional cohort study. Setting Two urban community health centres in Vancouver and Prince George, BC. Participants Two hundred sixty-nine HIV-positive patients (18 years of age or older) who received primary care at either of the study sites. Intervention Systematic implementation of the CCM during an 18-month period. Main outcome measures Documented pneumococcal vaccination, documented syphilis screening, documented tuberculosis screening, antiretroviral treatment (ART) status, ART status with undetectable viral load, CD4 cell count of less than 200 cells/mL, and CD4 cell count of less than 200 cells/mL while not taking ART compared during a 36-month period. Results Overall, 35% of participants were women and 59% were aboriginal persons. The mean age was 45 years and most participants had a history of injection drug use that was the presumed route of HIV transmission. During the study follow-up period, 39 people died, and 11 transferred to alternate care providers. Compared with their baseline clinical status, study participants showed statistically significant (P < .001 for all) increases in pneumococcal immunization (54% vs 84%), syphilis screening (56% vs 91%), tuberculosis screening (23% vs 38%), and antiretroviral uptake (47% vs 77%), as well as increased viral load suppression rates among those receiving ART (72% vs 90%). Stable housing at baseline was associated with a 4-fold increased probability of survival. Aboriginal ethnicity was not associated with better or worse outcomes at baseline or at follow-up. Conclusion Application of the CCM approach to HIV care in a marginalized, largely aboriginal patient population led to improved disease screening, immunization, ART uptake, and virologic suppression rates. In addition to addressing underlying social determinants of health, a paradigm shift away from an “infectious disease” approach to a “chronic disease management” approach to HIV care for marginalized populations is strongly recommended. PMID:23766052

Maternal CD4+ cell count decline after interruption of antiretroviral prophylaxis for the prevention of mother-to-child transmission of HIV.

PubMed

Ekouevi, Didier; Abrams, Elaine J; Schlesinger, Malka; Myer, Landon; Phanuphak, Nittaya; Carter, Rosalind J

2012-01-01

We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program. Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm(3) at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm(3) or <200 cells/mm(3) at 24 months. Weibull regression was used for multivariable analysis. A total of 1,393 women with enrollment CD4+ ≥250 cells/mm(3) initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23-30), median CD4+ was 469 cells/mm(3) (IQR: 363-613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm(3) was 12% (95% CI: 10-14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm(3) was 28%; (95% CI: 25-32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm(3): 46% (CD4+400-499 cells/mm(3)) vs. 19% (CD4+ ≥500 cells/mm(3)). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm(3) within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5-3.2, p<0.0001). Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected With HIV-1.

PubMed

Speranza, Francisco A B; Ishii, Solange K; Thuler, Luiz C S; Damasco, Paulo V; Hirata, Raphael; Mattos-Guaraldi, Ana L; Milagres, Lucimar G

2012-07-01

We assessed the IgG levels anti-diphtheria (D-Ab) and T cell counts (CD4+ and CD8+) in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART). Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml) than HAART-patients (geometric mean of 0.39 IU/ml). The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected With HIV-1

PubMed Central

Speranza, Francisco A. B.; Ishii, Solange K.; Thuler, Luiz C. S.; Damasco, Paulo V.; Jr, Raphael Hirata; Mattos-Guaraldi, Ana L.; Milagres, Lucimar G.

2012-01-01

We assessed the IgG levels anti-diphtheria (D-Ab) and T cell counts (CD4+ and CD8+) in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART). Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml) than HAART-patients (geometric mean of 0.39 IU/ml). The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination. PMID:24031911

CD4 Lymphocyte Enumeration and Hemoglobin Assessment Aid for Priority Decisions: A Multisite Evaluation of the BD FACSPresto™ System

PubMed Central

Thakar, Madhuri; Angira, Francis; Pattanapanyasat, Kovit; Wu, Alan H.B.; O’Gorman, Maurice; Zeng, Hui; Qu, Chenxue; Mahajan, Bharati; Sukapirom, Kasama; Chen, Danying; Hao, Yu; Gong, Yan; Indig, Monika De Arruda; Graminske, Sharon; Orta, Diana; d’Empaire, Nicole; Lu, Beverly; Omana-Zapata, Imelda; Zeh, Clement

2017-01-01

Background: The BD FACSPresto™ system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites. Methods: Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur™ system, and for Hb, using the Sysmex® KX-21N™ analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs. Results: For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96–1.05 and R2 ≥0.96; Hb slopes were ≥1.00 and R2 ≥0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot. Conclusion: The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems. PMID:29290885

CD4 Lymphocyte Enumeration and Hemoglobin Assessment Aid for Priority Decisions: A Multisite Evaluation of the BD FACSPresto™ System.

PubMed

Thakar, Madhuri; Angira, Francis; Pattanapanyasat, Kovit; Wu, Alan H B; O'Gorman, Maurice; Zeng, Hui; Qu, Chenxue; Mahajan, Bharati; Sukapirom, Kasama; Chen, Danying; Hao, Yu; Gong, Yan; Indig, Monika De Arruda; Graminske, Sharon; Orta, Diana; d'Empaire, Nicole; Lu, Beverly; Omana-Zapata, Imelda; Zeh, Clement

2017-01-01

The BD FACSPresto ™ system uses capillary and venous blood to measure CD4 absolute counts (CD4), %CD4 in lymphocytes, and hemoglobin (Hb) in approximately 25 minutes. CD4 cell count is used with portable CD4 counters in resource-limited settings to manage HIV/AIDS patients. A method comparison was performed using capillary and venous samples from seven clinical laboratories in five countries. The BD FACSPresto system was assessed for variability between laboratory, instrument/operators, cartridge lots and within-run at four sites. Samples were collected under approved voluntary consent. EDTA-anticoagulated venous samples were tested for CD4 and %CD4 T cells using the gold-standard BD FACSCalibur ™ system, and for Hb, using the Sysmex ® KX-21N ™ analyzer. Venous and capillary samples were tested on the BD FACSPresto system. Matched data was analyzed for bias (Deming linear regression and Bland-Altman methods), and for concordance around the clinical decision point. The coefficient of variation was estimated per site, instrument/operator, cartridge-lot and between-runs. For method comparison, 93% of the 720 samples were from HIV-positive and 7% from HIV-negative or normal subjects. CD4 and %CD4 T cells venous and capillary results gave slopes within 0.96-1.05 and R 2 ≥0.96; Hb slopes were ≥1.00 and R 2 ≥0.89. Variability across sites/operators gave %CV <5.8% for CD4 counts, <1.9% for %CD4 and <3.2% for Hb. The total %CV was <7.7% across instrument/cartridge lot. The BD FACSPresto system provides accurate, reliable, precise CD4/%CD4/Hb results compared to gold-standard methods, irrespective of venous or capillary blood sampling. The data showed good agreement between the BD FACSPresto, BD FACSCalibur and Sysmex systems.

Relationship of ethnicity and CD4 Count with glucose metabolism among HIV patients on Highly-Active Antiretroviral Therapy (HAART)

PubMed Central

2013-01-01

Background HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes. Methods Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined. Results African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW’s. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge. Conclusions Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response. PMID:23607267

Predictions of CD4 lymphocytes’ count in HIV patients from complete blood count

PubMed Central

2013-01-01

Background HIV diagnosis, prognostic and treatment requires T CD4 lymphocytes’ number from flow cytometry, an expensive technique often not available to people in developing countries. The aim of this work is to apply a previous developed methodology that predicts T CD4 lymphocytes’ value based on total white blood cell (WBC) count and lymphocytes count applying sets theory, from information taken from the Complete Blood Count (CBC). Methods Sets theory was used to classify into groups named A, B, C and D the number of leucocytes/mm3, lymphocytes/mm3, and CD4/μL3 subpopulation per flow cytometry of 800 HIV diagnosed patients. Union between sets A and C, and B and D were assessed, and intersection between both unions was described in order to establish the belonging percentage to these sets. Results were classified into eight ranges taken by 1000 leucocytes/mm3, calculating the belonging percentage of each range with respect to the whole sample. Results Intersection (A ∪ C) ∩ (B ∪ D) showed an effectiveness in the prediction of 81.44% for the range between 4000 and 4999 leukocytes, 91.89% for the range between 3000 and 3999, and 100% for the range below 3000. Conclusions Usefulness and clinical applicability of a methodology based on sets theory were confirmed to predict the T CD4 lymphocytes’ value, beginning with WBC and lymphocytes’ count from CBC. This methodology is new, objective, and has lower costs than the flow cytometry which is currently considered as Gold Standard. PMID:24034560

Prevalent and Incident Tuberculosis Are Independent Risk Factors for Mortality among Patients Accessing Antiretroviral Therapy in South Africa

PubMed Central

Gupta, Ankur; Wood, Robin; Kaplan, Richard; Bekker, Linda-Gail; Lawn, Stephen D.

2013-01-01

Background Patients with prevalent or incident tuberculosis (TB) in antiretroviral treatment (ART) programmes in sub-Saharan Africa have high mortality risk. However, published data are contradictory as to whether TB is a risk factor for mortality that is independent of CD4 cell counts and other patient characteristics. Methods/Findings This observational ART cohort study was based in Cape Town, South Africa. Deaths from all causes were ascertained among patients receiving ART for up to 8 years. TB diagnoses and 4-monthly CD4 cell counts were recorded. Mortality rates were calculated and Poisson regression models were used to calculate incidence rate ratios (IRR) and identify risk factors for mortality. Of 1544 patients starting ART, 464 patients had prevalent TB at baseline and 424 developed incident TB during a median of 5.0 years follow-up. Most TB diagnoses (73.6%) were culture-confirmed. A total of 208 (13.5%) patients died during ART and mortality rates were 8.84 deaths/100 person-years during the first year of ART and decreased to 1.14 deaths/100 person-years after 5 years. In multivariate analyses adjusted for baseline and time-updated risk factors, both prevalent and incident TB were independent risk factors for mortality (IRR 1.7 [95% CI, 1.2–2.3] and 2.7 [95% CI, 1.9–3.8], respectively). Adjusted mortality risks were higher in the first 6 months of ART for those with prevalent TB at baseline (IRR 2.33; 95% CI, 1.5–3.5) and within the 6 months following diagnoses of incident TB (IRR 3.8; 95% CI, 2.6–5.7). Conclusions Prevalent TB at baseline and incident TB during ART were strongly associated with increased mortality risk. This effect was time-dependent, suggesting that TB and mortality are likely to be causally related and that TB is not simply an epiphenomenon among highly immunocompromised patients. Strategies to rapidly diagnose, treat and prevent TB prior to and during ART urgently need to be implemented. PMID:23418463

Intensification of antiretroviral therapy through addition of enfuvirtide in naive HIV-1-infected patients with severe immunosuppression does not improve immunological response: results of a randomized multicenter trial (ANRS 130 Apollo).

PubMed

Joly, Véronique; Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

2013-02-01

We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm(3) or stage B/C disease with CD4 counts of <200/mm(3). Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥ 200/mm(3) at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm(3), and the median HIV-1 RNA load was 5.4 log(10) copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥ 200/mm(3) at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression.

Intensification of Antiretroviral Therapy through Addition of Enfuvirtide in Naive HIV-1-Infected Patients with Severe Immunosuppression Does Not Improve Immunological Response: Results of a Randomized Multicenter Trial (ANRS 130 Apollo)

PubMed Central

Fagard, Catherine; Grondin, Carine; Descamps, Diane; Yazdanpanah, Yazdan; Charpentier, Charlotte; Colin de Verdiere, Nathalie; Tabuteau, Sophie; Raffi, François; Cabie, André; Chene, Geneviève; Yeni, Patrick

2013-01-01

We studied whether addition of enfuvirtide (ENF) to a background combination antiretroviral therapy (cART) would improve the CD4 cell count response at week 24 in naive patients with advanced HIV disease. ANRS 130 Apollo is a randomized study, conducted in naive HIV-1-infected patients, either asymptomatic with CD4 counts of <100/mm3 or stage B/C disease with CD4 counts of <200/mm3. Patients received tenofovir-emtricitabine with lopinavir-ritonavir (LPV/r) or efavirenz and were randomized to receive ENF for 24 weeks (ENF arm) or not (control arm). The primary endpoint was the proportion of patients with CD4 counts of ≥200/mm3 at week 24. A total of 195 patients were randomized: 73% had stage C disease, 78% were male, the mean age was 44 years, the median CD4 count was 30/mm3, and the median HIV-1 RNA load was 5.4 log10 copies/ml. Eighty-one percent of patients received LPV/r. One patient was lost to follow-up, and eight discontinued the study (four in each arm). The proportions of patients with CD4 counts of ≥200/mm3 at week 24 were 34% and 38% in the ENF and control arms, respectively (P = 0.53). The proportions of patients with HIV-1 RNA loads of <50 copies/ml were 74% and 58% at week 24 in the ENF and control arms, respectively (P < 0.02), and the proportion reached 79% in both arms at week 48. Twenty (20%) and 12 patients (13%) in the ENF and control arms, respectively, experienced at least one AIDS event during follow-up (P = 0.17). Although inducing a more rapid virological response, addition of ENF to a standard cART does not improve the immunological outcome in naive HIV-infected patients with severe immunosuppression. PMID:23165467

Increased CD127+ and decreased CD57+ T cell expression levels in HIV-infected patients on NRTI-sparing regimens.

PubMed

Gonzalez-Serna, A; Ferrando-Martinez, S; Tarancon-Diez, L; De Pablo-Bernal, R S; Dominguez-Molina, B; Jiménez, J L; Muñoz-Fernández, M Á; Leal, M; Ruiz-Mateos, E

2017-12-20

NRTIs-sparing regimens exert favourable profiles on T-cell homeostasis associated parameters. Our aim was to analyze the effect of NRTIs sparing regimen (NRTI-sparing-cART) vs NRTIs-containing regimen (NRTI-cART), on T-cell homeostasis associated parameters in naive HIV-infected patients. Biomarkers of cell survival (CD127) and replicative senescence (CD57), were measured by multiparametric flow cytometry for T-cell phenotyping on peripheral blood mononuclear cells (PBMCs) samples just before (baseline) and after 48 weeks of undetectable viral load in patients on NRTI-sparing-cART (N = 13) and NRTI-cART (N = 14). After 48 weeks a subgroup of patients (n = 5) on NRTI-cART switched to NRTI-sparing-cART for another additional 48 weeks. In vitro assays were performed on PBMCs from HIV-uninfected healthy donors exposed or not to HIV. To analyze the independent factors associated with type of cART bivariate and stepwise multivariate analysis were performed after adjusting for basal CD4+, CD8+ and nadir CD4+ T-cell counts. After 48 weeks of a NRTI-sparing-cART vs NRTI-cART patients have higher effector memory (EM) CD4+ CD127+ T-cell levels, lower EM CD4+ CD57+ T-cell levels, higher CD8+ CD127+ T-cell levels, lower CD8+ CD57+ T-cell levels and higher memory CD8+ T-cell levels. This effect was confirmed in the subgroup of patients who switched to NRTI-sparing-cART. In vitro assays confirmed that the deleterious effect of a NRTIs-containing regimen was due to NRTIs. The implementation of NRTI-sparing regimens, with a favourable profile in CD127 and CD57 T-cell expression, could benefit cART-patients. These results could have potential implications in a decrease in the number of Non-AIDS events.

A Randomized, Controlled Trial of Mindfulness-Based Stress Reduction in HIV Infection.

PubMed

Hecht, Frederick M; Moskowitz, Judith T; Moran, Patricia; Epel, Elissa S; Bacchetti, Peter; Acree, Michael; Kemeny, Margaret E; Mendes, Wendy B; Duncan, Larissa G; Weng, Helen; Levy, Jay A; Deeks, Steven G; Folkman, Susan

2018-05-26

Evidence links depression and stress to more rapid progression of HIV-1 disease. We conducted a randomized controlled trial to test whether an intervention aimed at improving stress management and emotion regulation, mindfulness-based stress reduction (MBSR), would improve immunological (i.e. CD4+ t-cell counts) and psychological outcomes in persons with HIV-1 infection. We randomly assigned participants with HIV-1 infection and CD4 T-cell counts > 350 cells/μl who were not on antiretroviral therapy in a 1:1 ratio to either an MBSR group (n=89) or an HIV disease self-management skills group (n=88). The study was conducted at the University of California at San Francisco. We assessed immunologic (CD4, c-reactive protein, IL-6, and d-dimer) and psychological measures (Beck Depression Inventory for depression, modified Differential Emotions Scale for positive and negative affect, Perceived stress-scale, and mindfulness) at 3, 6 and 12 months after initiation of the intervention; we used multiple imputation to address missing values. We observed statistically significant improvements from baseline to 3-months within the MBSR group in depression, positive and negative affect, perceived stress, and mindfulness; between group differences in change were significantly greater in the MBSR group only for positive affect (per item difference on DES-positive 0.25, 95% CI 0.049, 0.44, p = .015). By 12 months the between group difference in positive affect was not statistically significant, although both groups had trends toward improvements compared to baseline in several psychological outcomes that were maintained at 12-months; these improvements were only statistically significant for depression and negative affect in the MBSR group and perceived stress for the control group. The groups did not differ significantly on rates of antiretroviral therapy initiation (MBSR = 39%, control = 29%, p = .22). After 12 months, the mean decrease in CD4+ T-cell count was 49.6 cells/μl in participants in the MBSR arm, compared to 54.2 cells/μl in the control group, a difference of 4.6 cells favoring the MBSR group (95% CI, -44.6, 53.7, p=.85). The between group differences in other immunologic-related outcomes (c-reactive protein, IL-6, HIV-1 viral load, and d-dimer) were not statistically significant at any time point. MBSR improved positive affect more than an active control arm in the 3 months following the start of the intervention. However, this difference was not maintained over the 12-month follow-up and there were no significant differences in immunologic outcomes between intervention groups. These results emphasize the need for further carefully designed research if we are to translate evidence linking psychological states to immunological outcomes into evidence-based clinical practices. Copyright © 2018. Published by Elsevier Inc.

A Quantitative Comparison of Anti-HIV Gene Therapy Delivered to Hematopoietic Stem Cells versus CD4+ T Cells

PubMed Central

Savkovic, Borislav; Nichols, James; Birkett, Donald; Applegate, Tanya; Ledger, Scott; Symonds, Geoff; Murray, John M.

2014-01-01

Gene therapy represents an alternative and promising anti-HIV modality to highly active antiretroviral therapy. It involves the introduction of a protective gene into a cell, thereby conferring protection against HIV. While clinical trials to date have delivered gene therapy to CD4+T cells or to CD34+ hematopoietic stem cells (HSC), the relative benefits of each of these two cellular targets have not been conclusively determined. In the present analysis, we investigated the relative merits of delivering a dual construct (CCR5 entry inhibitor + C46 fusion inhibitor) to either CD4+T cells or to CD34+ HSC. Using mathematical modelling, we determined the impact of each scenario in terms of total CD4+T cell counts over a 10 year period, and also in terms of inhibition of CCR5 and CXCR4 tropic virus. Our modelling determined that therapy delivery to CD34+ HSC generally resulted in better outcomes than delivery to CD4+T cells. An early one-off therapy delivery to CD34+ HSC, assuming that 20% of CD34+ HSC in the bone marrow were gene-modified (G+), resulted in total CD4+T cell counts ≥180 cells/ µL in peripheral blood after 10 years. If the uninfected G+ CD4+T cells (in addition to exhibiting lower likelihood of becoming productively infected) also exhibited reduced levels of bystander apoptosis (92.5% reduction) over non gene-modified (G-) CD4+T cells, then total CD4+T cell counts of ≥350 cells/ µL were observed after 10 years, even if initially only 10% of CD34+ HSC in the bone marrow received the protective gene. Taken together our results indicate that: 1.) therapy delivery to CD34+ HSC will result in better outcomes than delivery to CD4+T cells, and 2.) a greater impact of gene therapy will be observed if G+ CD4+T cells exhibit reduced levels of bystander apoptosis over G- CD4+T cells. PMID:24945407

Impact on ART initiation of point-of-care CD4 testing at HIV diagnosis among HIV-positive youth in Khayelitsha, South Africa.

PubMed

Patten, Gabriela E M; Wilkinson, Lynne; Conradie, Karien; Isaakidis, Petros; Harries, Anthony D; Edginton, Mary E; De Azevedo, Virginia; van Cutsem, Gilles

2013-07-04

Despite the rapid expansion of antiretroviral therapy (ART) programmes in developing countries, pre-treatment losses from care remain a challenge to improving access to treatment. Youth and adolescents have been identified as a particularly vulnerable group, at greater risk of loss from both pre-ART and ART care. Point-of-care (POC) CD4 testing has shown promising results in improving linkage to ART care. In Khayelitsha township, South Africa, POC CD4 testing was implemented at a clinic designated for youth aged 12-25 years. We assessed whether there was an associated reduction in attrition between HIV testing, assessment for eligibility and ART initiation. A before-and-after observational study was conducted using routinely collected data. These were collected on patients from May 2010 to April 2011 (Group A) when baseline CD4 count testing was performed in a laboratory and results were returned to the clinic within two weeks. Same-day POC CD4 testing was implemented in June 2011, and data were collected on patients from August 2011 to July 2012 (Group B). A total of 272 and 304 youth tested HIV-positive in Group A and Group B, respectively. Group B patients were twice as likely to have their ART eligibility assessed compared to Group A patients: 275 (90%) vs. 183 (67%) [relative risk (RR)=2.4, 95% CI: 1.8-3.4, p<0.0001]. More patients in World Health Organization (WHO) Stage 1 disease (85% vs. 69%), with CD4 counts≥350 cells/µL (58% vs. 35%) and more males (13% vs. 7%) were detected in Group B. The proportion of eligible patients who initiated ART was 50% and 44% (p=0.6) in Groups B and A, respectively; and 50% and 43% (p=0.5) when restricted to patients with baseline CD4 count≤250 cells/µL. Time between HIV-testing and ART initiation was reduced from 36 to 28 days (p=0.6). POC CD4 testing significantly improved assessment for ART eligibility. The improvement in the proportion initiating ART and the reduction in time to initiation was not significant due to sample size limitations. POC CD4 testing reduced attrition between HIV-testing and assessment of ART eligibility. Strategies to improve uptake of ART are needed, possibly by improving patient support for HIV-positive youth immediately after diagnosis.

Exclusion-Based Capture and Enumeration of CD4+ T Cells from Whole Blood for Low-Resource Settings.

PubMed

Howard, Alexander L; Pezzi, Hannah M; Beebe, David J; Berry, Scott M

2014-06-01

In developing countries, demand exists for a cost-effective method to evaluate human immunodeficiency virus patients' CD4(+) T-helper cell count. The TH (CD4) cell count is the current marker used to identify when an HIV patient has progressed to acquired immunodeficiency syndrome, which results when the immune system can no longer prevent certain opportunistic infections. A system to perform TH count that obviates the use of costly flow cytometry will enable physicians to more closely follow patients' disease progression and response to therapy in areas where such advanced equipment is unavailable. Our system of two serially-operated immiscible phase exclusion-based cell isolations coupled with a rapid fluorescent readout enables exclusion-based isolation and accurate counting of T-helper cells at lower cost and from a smaller volume of blood than previous methods. TH cell isolation via immiscible filtration assisted by surface tension (IFAST) compares well against the established Dynal T4 Quant Kit and is sensitive at CD4 counts representative of immunocompromised patients (less than 200 TH cells per microliter of blood). Our technique retains use of open, simple-to-operate devices that enable IFAST as a high-throughput, automatable sample preparation method, improving throughput over previous low-resource methods. © 2013 Society for Laboratory Automation and Screening.

Validation of a single-platform, volumetric, flow cytometry for CD4 T cell count monitoring in therapeutic mobile unit

PubMed Central

2012-01-01

Background A mobile health unit may be useful to follow up adult and pediatric patients on antiretroviral treatment and living in remote areas devoid of laboratory facilities. The study evaluated the use of the simplified, robust, single-plateform, volumetric, pan-leucogating Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) for CD4 T cell numeration in a mobile unit, compared against a reference flow cytometry method. Methods The therapeutic mobile unit of the Laboratoire National de Santé Hygiène Mobile, Yaoundé, Cameroon, was equipped with the Auto40. A FACSCalibur flow cytometer (Becton Dickinson Immuno-cytometry System, San Jose, CA, USA) was used as reference method. EDTA-blood samples from volunteers were first subjected to CD4 T cell count in the mobile unit, and an aliquot was sent within 4 hours to Centre International de Référence Chantal Biya, Yaoundé, for FACSCalibur assay. Results Two HIV screening campaigns with the mobile unit were organised in December 2009 and January 2010. The campaign in the suburb of Yaoundé which was 20 km from the reference laboratory included 188 volunteers comprising 93 children less than 5 years old. The campaign in Ambang Bikok (53 km far from Yaoundé) included 69 adult volunteers. In Yaoundé suburb, mean ± standard deviation (SD) CD4 T cell count was 996 ± 874 cells/μl by Auto40, and 989 ± 883 cells/μl by FACSCalibur; in Ambang Bikok, mean ± SD CD4 T cell count was 1041 ± 317 cells/μl by Auto40, and 1032 ± 294 cells/μl by FACSCalibur. Results by Auto40 and FACSCalibur were highly correlated in Yaoundé (r2 = 0.982) as in Ambang Bikok (r2 = 0.921). Bland-Altman analysis showed a close agreement between Auto40 and FACSCalibur results expressed in absolute count as in percentage in Yaoundé and Ambang Bikok. When pooling the 257 CD4 T cell count measurements, the Auto40 yielded a mean difference of +7.6 CD4 T cells/μl higher than by reference flow cytometry; and the sensitivity and specificity of Auto40 in enumerating absolute CD4 T cell counts of less than 200 cells/μl were 87% and 99%, respectively, and in enumerating absolute CD4 T cell counts of less than 350 cells/μl were 87% and 98%, respectively. The intrarun and interun precisions of the Auto40 assay assessed in the mobile unit were 5.5% and 7.9%, respectively. Conclusions The Auto40 flow cytometer installed in a therapeutic mobile unit and operated far from its reference laboratory gave a perfect correlation with the reference method, and could be useful in carrying out immunological monitoring of HIV-infected patients living in areas without access to laboratory facilities. PMID:22309994

Greater risk for viremia, immunosuppression, serious clinical events, and mortality with increasing age: the US perinatal HIV epidemic in its adolescence

PubMed Central

Neilan, Anne M.; Karalius, Brad; Patel, Kunjal; Van Dyke, Russell B.; Abzug, Mark J.; Agwu, Allison L.; Williams, Paige L.; Purswani, Murli; Kacanek, Deborah; Oleske, James M.; Burchett, Sandra K.; Wiznia, Andrew; Chernoff, Miriam; Seage, George R.; Ciaranello, Andrea L.

2017-01-01

Importance As perinatally HIV-infected youth (PHIVY) in the US grow older and more treatment-experienced, clinicians need updated information about the impact of age, CD4 count, viral load (VL), and antiretroviral drug (ARV) use on risks of opportunistic infections (OIs), key clinical events, and mortality in order to understand patient risks and improve care. Objective To determine the incidence or first occurrence during follow-up of key clinical events (including CDC-B and CDC-C events) and mortality among PHIVY stratified by age, CD4, and VL/ARV status. Design In the PHACS Adolescent Master Protocol (AMP) and IMPAACT P1074 multicenter cohort studies (2007–2015), we estimated event rates during person-time spent in key strata of age (7–12, 13–17, and 18–30 years), CD4 count (<200, 200–499, and ≥500 cells/μL), and VL/ARV status (< or ≥ 400 copies/mL; ARVs or no ARVs). Setting 41 ambulatory sites in the US, including Puerto Rico. Participants 1,562 participants in AMP and P1074 were eligible, 1446 PHIVY were included. Exposure(s) for observational studies Age, CD4 count, VL, ARV use. Main outcomes Clinical event rates stratified by person-time in age, CD4 count, and VL/ARV categories. Results During a mean follow-up of 4.9 years, higher incidences of CDC-B events, CDC-C events and mortality were observed as participants aged. Older PHIVY (13–17 and 18–30 year-olds) spent more time with VL ≥400 copies/mL and with CD4 <200/μL compared to 7–12 year-olds (30% and 44% vs. 22% of person-time with VL ≥400 copies/mL; 5% and 18% vs. 2% of person-time with CD4 <200/μL; p<0.01 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 counts, as expected. The mortality rate in older PHIVY was 6–12 times that of the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 counts, after adjusting for age. Conclusions and relevance Older PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ART adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY. PMID:28346597

CD4+ T cell count, HIV-1 viral loads and demographic variables of newly identified patients with HIV infection in Wuhan, China.

PubMed

Liu, Man-Qing; Tang, Li; Kong, Wen-Hua; Zhu, Ze-Rong; Peng, Jin-Song; Wang, Xia; Yao, Zhong-Zhao; Schilling, Robert; Zhou, Wang

2013-10-01

In China, the rate of human immunodeficiency virus (HIV) testing is increasing among men who have sex with men. The purpose of the present study was to describe HIV-related biomarkers and selected demographic variables of persons with newly diagnosed HIV/AIDS, among men who have sex with men in particular, in Wuhan China. Demographic indicators, and CD4+ T cell counts and HIV-1 viral load were collected from individuals newly identified as HIV-1 antibody positive during 2011. Of 176 enrolled patients, 132 (75.0%) were men who have sex with men. This group was significantly younger and had higher CD4+ T cell counts than patients who were likely infected through heterosexual contact. Most men who have sex with men (56.6%) were discovered by initiative investigation. Among heterosexual patients CD4+ T cell counts and HIV-1 viral load were significantly correlated; among the group of men who have sex with men, no such association was found. Copyright © 2013 Wiley Periodicals, Inc.

Marathon running increases circulating endothelial- and thrombocyte-derived microparticles.

PubMed

Schwarz, Viktoria; Düsing, Philip; Liman, Thomas; Werner, Christian; Herm, Juliane; Bachelier, Katrin; Krüll, Matthias; Brechtel, Lars; Jungehulsing, Gerhard J; Haverkamp, Wilhelm; Böhm, Michael; Endres, Matthias; Haeusler, Karl Georg; Laufs, Ulrich

2018-02-01

Background Acute vascular effects of high intensity physical activity are incompletely characterized. Circulating microparticles are cellular markers for vascular activation and damage. Methods Microparticles were analysed in 99 marathon runners (49 ± 6 years, 22% female) of the prospective Berlin Beat of Running study. Blood samples were taken within three days before, immediately after and within two days after the marathon run. Endothelial-derived microparticles were labelled with CD144, CD31 and CD62E, platelet-derived microparticles with CD62P and CD42b, leukocyte-derived microparticles with CD45 and monocyte-derived microparticles with CD14. Results Marathon running induced leukocytosis (5.9 ± 0.1 to 14.8 ± 0.3 10 9 /l, p < 0.0001) and increased platelet counts (239 ± 4.6 to 281 ± 5.9 10 9 /l, p < 0.0001) immediately after the marathon. Blood monocytes increased and lymphocytes decreased after the run ( p < 0.0001). Endothelial-derived microparticles were acutely increased ( p = 0.008) due to a 23% increase of apoptotic endothelial-derived microparticles ( p = 0.007) and returned to baseline within two days after the marathon. Thrombocyte-derived microparticles acutely increased by 38% accompanied by an increase in activated and apoptotic thrombocyte-derived microparticles ( p ≤ 0.0001) each. Both monocyte- and leukocyte-derived microparticles were decreased immediately after marathon run ( p < 0.0001) and remained below baseline until day 2. Troponin T increased from 12 to 32 ng/l ( p < 0.0001) immediately after the run and returned to baseline after two days. Conclusion Circulating apoptotic endothelial- and thrombocyte-derived microparticles increased after marathon running consistent with an acute pro-thrombotic and pro-inflammatory state. Exercise-induced vascular damage reflected by microparticles could indicate potential mechanisms of post-exertional cardiovascular complications. Further studies are warranted to investigate microparticles as markers to identify individuals prone to such complications.

Progression of varicella-zoster virus necrotizing retinopathy in an HIV-negative patient with transient immune deviation.

PubMed

Lim, Wee-Kiak; Chee, Soon-Phaik; Nussenblatt, Robert Burton

2005-06-01

To report a case of unilateral varicella-zoster virus (VZV) necrotizing retinopathy that progressed from outer retinitis with features of progressive outer retinal necrosis (PORN) to typical acute retinal necrosis (ARN) in an HIV-negative patient with a transient decrease in CD4 lymphocyte counts and CD4/CD8 ratio. Case report. A 41-year-old Chinese man presenting with blurred vision in the right eye was diagnosed with herpetic necrotizing retinitis without vitritis. Fundus examination revealed retinal arteritis and extensive deep whitish retinal lesions in the mid-periphery with minimal vitritis. Aqueous humor and vitreous PCR were positive for VZV. His CD4 count on presentation was depressed (239 cells/ul) and the CD4/CD8 ratio was low (0.8). The referring ophthalmologist had treated him with prednisolone 60 mg/day. At our institution, when intravenous acyclovir was started and the steroid therapy discontinued, he developed severe vitritis and the deep retinal lesions progressed to full-thickness retinitis typical of ARN. Repeat CD4 count was 512 cells/ul at day 14. In total, he was treated with 14 days of i.v. acyclovir (12 mg/kg 8-hourly) followed by oral valaciclovir 500 mg three times a day for 3 months. Prednisolone 30 mg once daily was restarted and tapered over 3 months. Despite prophylactic argon retinal photocoagulation to the edge of the retinitis, the patient developed a total retinal detachment at 3 months. VZV retinal infection in an HIV-negative patient with transient immune deviation can manifest initially as outer retinitis with features similar to PORN and progress to typical ARN when CD4 counts return to normal.

Poor agreement between diagnostic tests for latent tuberculosis infection among HIV-infected persons in Hong Kong.

PubMed

Leung, Chi Chiu; Chan, Kenny; Yam, Wing Cheong; Lee, Man Po; Chan, Chi Kuen; Wong, Ka Hing; Ho, Pak Leung; Mak, Ida; Tam, Cheuk Ming

2016-10-01

The tuberculin skin test (TST), T-Spot.TB (T-Spot) and QuantiFERON-TB Gold-In Tube (QFT) were compared in diagnosing latent tuberculosis infection (LTBI) among human immunodeficiency virus (HIV)-infected persons. Human immunodeficiency virus-infected persons without previous history of tuberculosis or LTBI were simultaneously tested by TST, T-Spot and QFT annually and followed up for tuberculosis. Among 110 HIV-infected subjects with 85% previous TST screening coverage, 75% on anti-retroviral therapy, well-preserved median CD4 count (414/μL) and low median viral load (<75/μL), baseline TST, T-Spot and QFT were positive in 5.5%, 5.6% and 4.9%, respectively, with almost complete discordance of positive results. Among 91 (83%), 66 (60%) and 26 (24%) subjects successfully undergoing the first, second and third annual retesting, TST, T-Spot and QFT were, respectively, positive in 11/123 (8.9%), 13/173 (7.5%) and 21/182 (11.5%) on retesting, with similar discordance of positive results. There was no significant association with the concurrent CD4 count or viral load. Conversion occurred in 11/123 (8.9%), 8/160 (5.0%) and 18/168 (10.7%) of TST, T-Spot and QFT, respectively, and none was associated with changes in CD4 count or viral load. More than half of the positive T-SPOT and QFT results reverted to negative on follow-up. None of these tests picked up the single case of culture-confirmed tuberculosis observed after 798 person-years of follow-up. Major discordance in positive results, high reversion rates and low tuberculosis incidence among test-positive subjects cast serious doubt on the utility of the currently available LTBI tests in the annual screening of HIV-infected persons in an intermediate tuberculosis burden area. © 2016 Asian Pacific Society of Respirology.

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

PubMed

Palefsky, Joel M; Holly, Elizabeth A; Efirdc, Jimmy T; Da Costa, Maria; Jay, Naomi; Berry, J Michael; Darragh, Teresa M

2005-09-02

The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

Health-related quality of life among military HIV patients on antiretroviral therapy.

PubMed

Emuren, Leonard; Welles, Seth; Evans, Alison A; Polansky, Marcia; Okulicz, Jason F; Macalino, Grace; Agan, Brian K

2017-01-01

The aims of this study were: (i) to determine the factors associated with HRQOL at baseline in our cohort, and (ii) to evaluate if there are differences in baseline HRQOL measures by antiretroviral treatment. The Short Form 36 (SF-36) was administered between 2006 and 2010 among members of the United States HIV Natural History Study cohort (NHS), and participants who completed the SF-36 were included in the study. Physical component summary (PCS) and mental component summary (MCS) scores were computed based on standard algorithms. Multivariate linear regression models were constructed for PCS and MCS to estimate the association between selected variables and HRQOL scores. Antiretroviral therapy (ART) was not independently associated with HRQOL scores. Factors associated with PCS were CD4+ count < 200 cells/mm3 (β = -5.84, 95% CI: -7.63, -4.06), mental comorbidity (β = -2.82, 95% CI: -3.79, -1.85), medical comorbidity (β = -2.51, 95% CI: -3.75, -1.27), AIDS diagnosis (β = -2.38, 95% CI: -3.79, -0.98). Others were gender, military rank, marital status, and age. Factors independently associated with MCS were CD4+ count < 200 cells/mm3 (β = -1.93, 95% CI: -3.85, -0.02), mental comorbidity (β = -6.25, 95% CI: -7.25, -5.25), age (β = 0.37, 95% CI: 0.14, 0.60), and being African American (β = 1.55, 95% CI: 0.63, 2.47). Among military active duty and beneficiaries with HIV, modifiable factors associated with HRQOL measures included advanced HIV disease, and mental or medical comorbidity. Addressing these factors may improve quality of life of HIV-infected individuals in the NHS cohort.

Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals.

PubMed

Yarasheski, Kevin E; Scherzer, Rebecca; Kotler, Donald P; Dobs, Adrian S; Tien, Phyllis C; Lewis, Cora E; Kronmal, Richard A; Heymsfield, Steven B; Bacchetti, Peter; Grunfeld, Carl

2011-03-01

Skeletal muscle (SM) mass decreases with advanced age and with disease in HIV infection. It is unknown whether age-related muscle loss is accelerated in the current era of antiretroviral therapy and which factors might contribute to muscle loss among HIV-infected adults. We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls. Whole-body (1)H-magnetic resonance imaging was used to quantify regional and total SM in 399 HIV-infected and 204 control men and women at baseline and 5 years later. Multivariable regression identified associated factors. At baseline and Year 5, total SM was lower in HIV-infected than control men. HIV-infected women were similar to control women at both time points. After adjusting for demographics, lifestyle factors, and total adipose tissue, HIV infection was associated with lower Year 5 SM in men and higher SM in women compared with controls. Average overall 5-year change in total SM was small and age related, but rate of change was similar in HIV-infected and control men and women. CD4 count and efavirenz use in HIV-infected participants were associated with increasing SM, whereas age and stavudine use were associated with decreasing SM. Muscle mass was lower in HIV-infected men compared with controls, whereas HIV-infected women had slightly higher SM than control women after multivariable adjustment. We found evidence against substantially faster SM decline in HIV infected versus similar-aged controls. SM gain was associated with increasing CD4 count, whereas stavudine use may contribute to SM loss.

Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa.

PubMed

Pantazis, Nikos; Morrison, Charles; Amornkul, Pauli N; Lewden, Charlotte; Salata, Robert A; Minga, Albert; Chipato, Tsungai; Jaffe, Harold; Lakhi, Shabir; Karita, Etienne; Porter, Kholoud; Meyer, Laurence; Touloumi, Giota

2012-01-01

It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations. We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA. Of 1,959 (913 non-Africans, 302 Europeans-African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15-29 year old woman was 607 (588-627) (non-African European), 469 (442-497) (European-African origin) and 570 (551-589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228-289), 155 (110-200), and 199 (174-224) cells/µL (p<0.01). Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.

Atypical manifestation of progressive outer retinal necrosis in AIDS patient with CD4+ T-cell counts more than 100 cells/microL on highly active antiretroviral therapy.

PubMed

Vichitvejpaisal, Pornpattana; Reeponmahar, Somporn; Tantisiriwat, Woraphot

2009-06-01

Typical progressive outer retinal necrosis (PORN) is an acute ocular infectious disease in acquired immunodeficiency syndrome (AIDS) patients with extremely low CD4+ T-cell counts. It is a form of the Varicella- zoster virus (VZV) infection. This destructive infection has an extremely rapid course that may lead to blindness in affected eyes within days or weeks. Attempts at its treatment have had limited success. We describe the case of a bilateral PORN in an AIDS patient with an initial CD4+ T-cell count >100 cells/microL that developed after initiation of highly active antiretroviral therapy (HAART). A 29-year-old Thai female initially diagnosed with human immunodeficiency virus (HIV) in 1998, presented with bilaterally decreased visual acuity after initiating HAART two months earlier. Multiple yellowish spots appeared in the deep retina without evidence of intraocular inflammation or retinal vasculitis. Her CD4+ T-cell count was 127 cells/microL. She was diagnosed as having PORN based on clinical features and positive VZV in the aqueous humor and vitreous by polymerase chain reaction (PCR). Despite combined treatment with intravenous acyclovir and intravitreous ganciclovir, the patient's visual acuity worsened with no light-perception in either eye. This case suggests that PORN should be included in the differential diagnosis of reduced visual acuity in AIDS patients initiating HAART with higher CD4+ T-cell counts. PORN may be a manifestation of the immune reconstitution syndrome.

Depression and CD4 cell count among patients with HIV in a Nigerian University Teaching Hospital.

PubMed

Olisah, Victor Obiajulu; Adekeye, Oluwatosin; Sheikh, Taiwo Lateef

2015-01-01

Depression is common in people living with HIV/AIDS and there is some evidence that depressive symptoms may have adverse effects on immune functioning. The purpose of this study was to determine the prevalence of current depressive disorder in patients with HIV/AIDS and its association with CD4 cell count. A consecutive sample of 310 patients with HIV/AIDS attending Out-patient clinic in Ahmadu Bello University Teaching Hospital (A.B.U.T.H.), Zaria, Nigeria was assessed. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to screen for depressive symptoms, and the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used to confirm the diagnosis of current depressive disorder. The CD4 cell counts of participants with depressive disorder were compared with those of participants without depressive disorder. Multiple regression analysis was conducted to identify socio-demographic and disease-related factors associated with depression. Among the 310 HIV-infected participants assessed for depression, 14.2% had current depressive disorder. Adjusting for age, gender, education, occupation, and marital status, patients with CD4 counts < 150 cells/μl were more likely to be depressed. Depression is common among HIV-infected persons in Nigeria and is associated with low CD4 cell counts. The screening and treatment of mental health problems such as depression should be considered an integral component of HIV care and support. © 2015, The Author(s).

Impact of nurse-delivered community-based CD4 services on facilitating pre-ART care in rural South Africa.

PubMed

Kompala, T; Moll, A P; Mtungwa, N; Brooks, R P; Friedland, G H; Shenoi, S V

2016-08-11

HIV testing, diagnosis and treatment programs have expanded globally, particularly in resource-limited settings. Diagnosis must be followed by determination of treatment eligibility and referral to care prior to initiation of antiretroviral treatment (ART). However, barriers and delays along these early steps in the treatment cascade may impede successful ART initiation. New strategies are needed to facilitate the treatment cascade. We evaluated the role of on site CD4+ T cell count phlebotomy services by nurses in facilitating pre-ART care in a community-based voluntary counseling and testing program (CBVCT) in rural South Africa. We retrospectively evaluated CBVCT services during five continuous time periods over three years: three periods when a nurse was present on site, and two periods when the nurse was absent. When a nurse was present, CD4 count phlebotomy was performed immediately after HIV testing to determine ART eligibility. When a nurse was absent, patients were referred to their local primary care clinic for CD4 testing. For each period, we determined the proportion of HIV-positive community members who completed CD4 testing, received notification of CD4 count results, as well as the time to test completion and result notification. Between 2010 and 2013, 7213 individuals accessed CBVCT services; of these, 620 (8.6 %) individuals were HIV-positive, 205 (33.1 %) were eligible for ART according to South African national CD4 count criteria, and 78 (38.0 % of those eligible) initiated ART. During the periods when a professional nurse was available to provide CD4 phlebotomy services, HIV-positive clients were significantly more likely to complete CD4 testing than during periods when these services were not available (85.5 % vs. 37.3 %, p < 0.001). Additionally, when nurses were present, individuals were significantly more likely to be notified of CD4 results (60.6 % vs. 26.7 %, p <0.001). The time from HIV screening to CD4 test completion was also significantly shorter during nurse presence than nurse absence (median 8 days (IQR 4-19) vs. 35 days (IQR 15-131), p < 0.001). These findings indicate that in addition to CBVCT, availability of on site CD4 phlebotomy may reduce loss along the pre-ART care cascade and facilitate timely entry into HIV care.

Age, sex, and nutritional status modify the CD4+ T-cell recovery rate in HIV-tuberculosis co-infected patients on combination antiretroviral therapy.

PubMed

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-06-01

Baseline age and combination antiretroviral therapy (cART) were examined as determinants of CD4+ T-cell recovery during 6 months of tuberculosis (TB) therapy with/without cART. It was determined whether this association was modified by patient sex and nutritional status. This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+ T-cell counts were measured using flow cytometry. Age was defined as ≤24, 25-29, 30-34, and 35-39 vs. ≥40 years. Nutritional status was defined as normal (>18.5kg/m(2)) vs. underweight (≤18.5kg/m(2)) using the body mass index (BMI). Multivariate random effects linear mixed models were fitted to estimate differences in CD4+ T-cell recovery in relation to specified determinants. cART was associated with a monthly rise of 15.7 cells/μl (p<0.001). Overall, age was not associated with CD4+ T-cell recovery during TB therapy (p = 0.655). However, among patients on cART, the age-associated CD4+ T-cell recovery rate varied by sex and nutritional status, such that age <40 vs. ≥40 years predicted superior absolute CD4+ T-cell recovery among females (p=0.006) and among patients with a BMI ≥18.5kg/m(2) (p<0.001). TB-infected HIV-positive patients aged ≥40 years have a slower rate of immune restoration given cART, particularly if BMI is >18.5kg/m(2) or they are female. These patients may benefit from increased monitoring and nutritional support during cART. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Age, Sex & Nutritional Status Modify CD4+T-Cell Recovery Rate in HIV/Tuberculosis Co-infected Patients on cART

PubMed Central

Ezeamama, Amara E; Mupere, Ezekiel; Oloya, James; Martinez, Leonardo; Kakaire, Robert; Yin, Xiaoping; Sekandi, Juliet N; Whalen, Christopher C

2015-01-01

Background We examined baseline age and combination antiretroviral therapy (cART) as determinants of CD4+T-cell recovery during six months of tuberculosis (TB) therapy with/without cART. We determined whether this association was modified by patient sex and nutritional status. Methods This longitudinal analysis included 208 immune-competent, non-pregnant, ART-naive HIV-positive patients from Uganda with a first episode of pulmonary TB. CD4+T-cell count was measured using flow cytometry. Age was defined as ≤24, 25–29, 30–34, 35–39 vs. ≥ 40 years. Nutritional status was defined as normal (>18.5kg/m2) vs. underweight (≤18.5kg/m2) using body mass index (BMI). Multivariate random-effects linear mixed models were fitted to estimate differences in CD4+T-cell recovery in relation to specified determinants. Results cART was associated with a monthly rise of 15.7 cells/μL (p<0.001). Overall, age was not associated with CD4+T-cell recovery during TB therapy (p=0.655). However, among patients on cART, age-associated CD4+T-cell recovery rate varied by sex and nutritional status such that age <40 vs. ≥ 40 years predicted superior absolute CD4+T-cell recovery among females (p=0.006) and among patients with BMI≥18.5kg/m2 (p<0.001). Conclusions TB infected HIV-positive patients ≥ 40 years have a slower rate of immune restoration given cART-particularly if BMI>18.5kg/m2 or female. They may benefit from increased monitoring and nutritional support during cART. PMID:25910854

Late presentation to HIV testing is overestimated when based on the consensus definition.

PubMed

Sasse, A; Florence, E; Pharris, A; De Wit, S; Lacor, P; Van Beckhoven, D; Deblonde, J; Delforge, M-L; Fransen, K; Goffard, J-C; Legrand, J-C; Moutschen, M; Piérard, D; Ruelle, J; Vaira, D; Vandercam, B; Van Ranst, M; Van Wijngaerden, E; Vandekerckhove, L; Verhofstede, C

2016-03-01

In 2011, a consensus was reached defining "late presenters" (LPs) as individuals presenting for care with a CD4 count < 350 cells/μL or with an AIDS-defining event, regardless of CD4 count. However, a transient low CD4 count is not uncommon in recent infections. The objective of this study was to investigate how measurements of late presentation change if the clinical stage at the time of diagnosis is taken into account. Case surveillance data for newly diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at diagnosis, the presence of AIDS-defining events, and recent infections (< 6 months) as reported by clinicians in the case of acute illness or a recent negative test. First, proportions of LPs were calculated according to the consensus definition. Secondly, LPs were reclassified as "nonlate" if infections were reported as recent. A total of 7949 HIV diagnoses were included in the study. Recent infections were increasingly reported over time, accounting for 8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical stage significantly modified the proportion of LPs: 18.2% of men who have sex with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9% using the consensus definition (P < 0.001). The proportion of patients misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41% in 2012. This study suggests that low CD4 counts in recent infections may lead to overestimation of late presentation when applying the consensus definition. The impact of transient CD4 count on late presentation estimates should be assessed and, if relevant, the introduction of clinical stage in the definition of late presentation should be considered. © 2015 British HIV Association.

Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database

PubMed Central

2012-01-01

Background Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality. Methods TAHOD patients with prospective follow up had data extracted for prophylaxis using co-trimoxazole, dapsone or pentamidine. The proportion of patients on prophylaxis was calculated for each calendar year since 2003 among patients with CD4 counts of less than 200 cells/mm3. The effect of prophylaxis on PCP and survival were assessed using random-effect Poisson regression models. Results There were a total of 4050 patients on prospective follow up, and 90% of them were receiving combination antiretroviral therapy. Of those with CD4 counts of less than 200 cells/mm3, 58% to 72% in any given year received PCP prophylaxis, predominantly co-trimoxazole. During follow up, 62 patients developed PCP (0.5 per 100 person-years) and 169 died from all causes (1.36/100 person-years). After stratifying by site and adjusting for age, CD4 count, CDC stage and antiretroviral treatment, those without prophylaxis had no higher risk of PCP, but had a significantly higher risk of death (incident rate ratio 10.8, p < 0.001). PCP prophylaxis had greatest absolute benefit in patients with CD4 counts of less than 50 cells/mm3, lowering mortality rates from 33.5 to 6.3 per 100 person-years. Conclusions Approximately two-thirds of TAHOD patients with CD4 counts of less than 200 cells/mm3 received PCP prophylaxis. Patients without prophylaxis had significantly higher mortality, even in the era of combination ART. Although PCP may be under-diagnosed, these data suggest that prophylaxis is associated with important survival benefits. PMID:22281054

[An analysis of immunophenotyping of peripheral lymphocytes in adult patients with infectious mononucleosis and chronic active Epstein-Barr virus infection].

PubMed

Xie, J; Wang, H L; Qiu, Z F; Li, T S

2016-06-01

To determine the immunophenotypic features of peripheral lymphocytes in adult patients with Epstein-Barr virus(EBV)-associated infectious mononucleosis(IM) and chronic active EBV infection (CAEBV). Eighteen IM patients, 12 CAEBV patients and 18 healthy donors were included. Lymphocyte subsets including CD3(-)CD19(+) B cells, CD3(-)CD16/56(+) NK cells, CD4(+) and CD8(+) T cells in peripheral blood were measured by flow cytometry. The expression of activation markers (HLA-DR and CD38) on CD8(+) T cells and CD28 expression on T cells were also determined. Kruskal-Wallis H and Mann-Whitney U tests were used to compare variables among groups. IM patients had dramatically increased CD8(+) T cell counts than healthy donors (5.22×10(9)/L vs 0.54×10(9)/L, P<0.001). B cell counts moderately reduced in patients with IM than in healthy donors. No difference was found in absolute CD4(+) T cell and NK cell counts between IM and healthy donors. The levels of HLA-DR and CD38 on CD8(+) T cells significantly increased in IM patients compared with those in healthy controls. The intensity of CD28 on CD8(+) T cells significantly decreased, which was not seen on CD4(+) T cells. The median cell counts of B, NK, CD4(+) T and CD8(+) T subsets in CAEBV patients were 0.02×10(9)/L, 0.06×10(9)/L, 0.26×10(9)/L and 0.21×10(9)/L respectively, which were significantly lower than those in healthy donors (0.22×10(9)/L, 0.38×10(9)/L, 0.78×10(9)/L, 0.54×10(9)/L)and IM patients (0.12×10(9)/L, 0.40×10(9)/L, 0.91×10(9)/L, 5.22×10(9)/L). The positive rates of HLA-DR and CD38 on CD8(+) T cells in CAEBV patients were higher than those in healthy controls, but lower than those in IM patients. The immunophenotypic pattern in adult patients with IM is characterized by a dramatic increase of extensively activated CD8(+) T cells, a moderate reduction of CD19(+) B cells and no significant change of CD4(+) T cells and CD16/56(+) NK cells. CAEBV is featured by an immunosuppression status as demonstrated by significantly decreased B, NK, CD4(+) T and CD8(+) T subsets.

Raltegravir versus Efavirenz regimens in treatment-naive HIV-1-infected patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses.

PubMed

Lennox, Jeffrey L; Dejesus, Edwin; Berger, Daniel S; Lazzarin, Adriano; Pollard, Richard B; Ramalho Madruga, Jose Valdez; Zhao, Jing; Wan, Hong; Gilbert, Christopher L; Teppler, Hedy; Rodgers, Anthony J; Barnard, Richard J O; Miller, Michael D; Dinubile, Mark J; Nguyen, Bach-Yen; Leavitt, Randi; Sklar, Peter

2010-09-01

We analyzed the 96-week results in the overall population and in prespecified subgroups from the ongoing STARTMRK study of treatment-naive HIV-infected patients. Eligible patients with HIV-1 RNA (vRNA) levels >5000 copies per milliliter and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. At week 96 counting noncompleters as failures, 81% versus 79% achieved vRNA levels <50 copies per milliliter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 2% (-4 to 9), noninferiority P < 0.001]. Mean change in baseline CD4 count was 240 and 225 cells per cubic millimeter in the raltegravir and efavirenz groups, respectively [Delta (95% confidence interval) = 15 (-13 to 42)]. Treatment effects were consistent across prespecified baseline demographic and prognostic subgroups. Fewer drug-related clinical adverse events (47% versus 78%; P < 0.001) occurred in raltegravir than efavirenz recipients. Both regimens had modest effects on serum lipids and glucose levels and on body fat composition. When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir exhibited durable antiretroviral activity that was noninferior to the efficacy of efavirenz through 96 weeks of therapy. Subgroup analyses were generally consistent with the overall findings. Both regimens were well tolerated.

Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals

PubMed Central

Okulicz, Jason F.; Le, Tuan D.; Agan, Brian K.; Camargo, Jose F.; Landrum, Michael L.; Wright, Edwina; Dolan, Matthew J.; Ganesan, Anuradha; Ferguson, Tomas M.; Smith, Davey M.; Richman, Douglas D.; Little, Susan J.; Clark, Robert A.; He, Weijing; Ahuja, Sunil K.

2014-01-01

IMPORTANCE In individuals with human immunodeficiency virus 1 (HIV-1) infection who are receiving antiretroviral therapy (ART), factors that promote full immune recovery are not well characterized. OBJECTIVE To investigate the influence of the timing of ART relative to HIV-1 infection on normalization of CD4+ T-cell counts, AIDS risk, and immune function. DESIGN, SETTING, AND PARTICIPANTS Participants in the observational US Military HIV Natural History Study with documented estimated dates of seroconversion (EDS) who achieved virologic suppression with ART were evaluated. Markers indicative of immune activation, dysfunction, and responsiveness were determined. Responses to hepatitis B virus (HBV) vaccine, an indicator of in vivo immune function, were also assessed. The timing of ART was indexed to the EDS and/or entry into the cohort. The CD4+ counts in HIV-1–uninfected populations were surveyed. MAIN OUTCOMES AND MEASURES Normalization of CD4+ counts to 900 cells/μL or higher, AIDS development, HBV vaccine response, as well as T-cell activation, dysfunction, and responsiveness. RESULTS The median CD4+ count in HIV-1–uninfected populations was approximately 900 cells/μL. Among 1119 HIV-1–infected participants, CD4+ normalization was achieved in 38.4% vs 28.3% of those initiating ART within 12 months vs after 12 months from the EDS (P = .001). Incrementally higher CD4+ recovery (<500,500–899, and ≥900 cells/μL) was associated with stepwise decreases in AIDS risk and reversion of markers of immune activation, dysfunction, and responsiveness to levels approximating those found in HIV-1–uninfected persons. Participants with CD4+ counts of 500 cells/μL or higher at study entry (adjusted odds ratio [aOR], 2.00; 95% CI, 1.51–2.64; P < .001) or ART initiation (aOR, 4.08; 95% CI, 3.14–5.30; P < .001) had significantly increased CD4+ normalization rates compared with other participants. However, even among individuals with a CD4+ count of 500 cells/μL or higher at both study entry and before ART, the odds of CD4+ normalization were 80% lower in those initiating ART after 12 months from the EDS and study entry (aOR, 0.20; 95% CI, 0.07–0.53; P = 001). Initiation of ART within 12 months of EDS vs later was associated with a significantly lower risk of AIDS (7.8% vs 15.3%; P = .002), reduced T-cell activation (percent CD4+HLA-DR+ effector memory T cells, 12.0% vs 15.6%; P = .03), and increased responsiveness to HBV vaccine (67.9% vs 50.9%; P = .07). CONCLUSIONS AND RELEVANCE Deferral of ART beyond 12 months of the EDS diminishes the likelihood of restoring immunologic health in HIV-1–infected individuals. PMID:25419650

Correlation between Lymphocyte CD4 Count, Treatment Duration, Opportunistic Infection and Cognitive Function in Human Immunodeficiency Virus-Acquired Immunodeficiency Syndrome (HIV-AIDS) Patients.

PubMed

Fitri, Fasihah Irfani; Rambe, Aldy Safruddin; Fitri, Aida

2018-04-15

Human immunodeficiency virus (HIV) infection is an epidemic worldwide, despite the marked benefits of antiretroviral therapy (ARV) in reducing severe HIV-associated dementia. A milder form of neurocognitive disorders are still prevalent and remain a challenge. This study aimed to determine the correlation between plasma cluster of differentiation 4 (CD4) lymphocyte, duration of ARV treatment, opportunistic infections, and cognitive function in HIV-AIDS patients. A cross-sectional study involving 85 HIV-AIDS patients was conducted at Adam Malik General Hospital Medan, Indonesia. All subjects were subjected to physical, neurologic examination and Montreal Cognitive Assessment-Indonesian Version (MoCA-INA) to assess cognitive function and measurement of lymphocyte CD4 counts. Out of the 85 subjects evaluated, the proportion concerning sexes include 52 males (61.2 %) and 33 females (38.8%). The mean age was 38.53 ± 9.77 years old. There was a significant correlation between CD4 lymphocyte counts and MoCA-INA score (r = 0.271, p = 0.012), but there was no significant correlation between duration of ARV treatment and MoCA-INA score. There was also no difference in MoCA-INA score based on the presence of opportunistic infection. Lymphocyte CD4 count was independently correlated with cognitive function in HIV-AIDS patients.

Antiretroviral therapy protects against frailty in HIV-1 infection.

PubMed

Ianas, Voichita; Berg, Erik; Mohler, M Jane; Wendel, Christopher; Klotz, Stephen A

2013-01-01

HIV-1-infected patients are surviving longer and by 2015 half will be older than 50 years of age. Frailty is a syndrome associated with advanced age but occurs in HIV-1-infected patients at younger ages. One hundred outpatient HIV-1-infected persons were prospectively tested for clinical markers of frailty: shrinking weight, slowness in walking, decrease in grip strength, low activity, and exhaustion. Age, length of infection with HIV, CD4 count, HIV-1 RNA, and comorbidities were compared. CD4 counts <200 cells/mm(3) were associated with 9-fold increased odds of frailty relative to patients with a CD4 count >350 cells/mm(3) (odds ratio [OR] 9.0, 95% confidence interval [CI] 2.1-44). Seven frail patients were measured 6 months later: 2 died refusing therapy, 4 were no longer frail, and 1 patient remained frail. We conclude that frailty is common in HIV outpatients and is associated with low CD4 counts. However, our data suggest that frailty is transient, especially in younger patients who may revert to their prefrail state unlike uninfected elderly individuals in whom a stepwise decline in function occurs.

The association between cigarette smoking, virologic suppression, and CD4+ lymphocyte count in HIV-Infected Russian women.

PubMed

Brown, Jennifer L; Winhusen, Theresa; DiClemente, Ralph J; Sales, Jessica M; Rose, Eve S; Safonova, Polina; Levina, Olga; Belyakov, Nikolay; Rassokhin, Vadim V

2017-09-01

Cigarette smoking among people living with HIV/AIDS is associated with significant morbidity and mortality, but findings regarding the association between cigarette smoking and HIV viral load and CD4+ lymphocyte counts have been inconsistent. This study characterized the prevalence of cigarette smoking among HIV-infected Russian women and examined the association between smoking frequency and quantity and HIV viral load and CD4+ lymphocyte counts. HIV-infected Russian women (N = 250; M age = 30.0) in St. Petersburg, Russia, completed an audio computer-assisted self-interview survey assessing cigarette use, antiretroviral medication adherence, and provided blood samples assayed for HIV viral load and CD4+ lymphocyte counts. The majority (60.4%) reported cigarette smoking in the past month; 49.0% of recent smokers were classified as moderate or heavy smokers, defined as smoking ≥10 cigarettes daily. Viral load status did not differ between infrequent smokers and regular smokers. However, moderate/heavy smokers (relative to light smokers) were more likely to have a detectable viral load (AOR = 2.3, 95% CI: 1.1, 5.1). There were no significant differences in CD4+ lymphocyte counts by smoking frequency or quantity of cigarettes smoked. Results highlight the need for additional research to examine the association between cigarette smoking and virologic suppression and markers of HIV disease progression. Adverse health consequences of cigarette smoking coupled with a potential link between heavy smoking and poor virologic suppression highlight the need for assessment of cigarette use and provision of evidence-based smoking-cessation interventions within HIV medical care.

The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests.

PubMed

Wang, Yu-Tong; Zhao, Xiang-Yu; Zhao, Xiao-Su; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Liu, Kai-Yan; Chang, Ying-Jun; Huang, Xiao-Jun

2015-12-01

The association of donor characteristics with immune cell composition in allografts remains poorly understood. In this retrospective study, the effects of donor characteristics on immune cell composition in allografts were investigated. The correlations of donor characteristics with the immune cell composition in mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests of 390 healthy donors (male, 240; female, 150; median age, 40 years old) were analyzed. The median doses of CD3+ T cells, CD4+ T cells, CD8+ T cells, CD3+CD4-CD8- T cells, and monocytes in mixture allografts were 160.57 × 10(6), 89.29 × 10(6), 56.16 × 10(6), 10.87 × 10(6), and 137.94 × 10(6)/kg, respectively. Multivariate analysis showed that younger donor age was associated with a higher dose of CD3+ T cells (p = 0.006), CD3+CD8+ T cells (p < 0.001), CD3+CD4-CD8- T cells (p = 0.004), and monocytes (p = 0.014), as well as a higher ratio of CD3+CD4-CD8- T cells/CD3+ T cells (p < 0.001) in the mixture allografts. A negative association of donor weight with CD3+ T cells (p < 0.001), CD4+ T cells (p = 0.002), CD8+ T cells (p < 0.001), and CD3+CD4-CD8- T cells (p = 0.044) was observed. The count of peripheral blood lymphocyte pre-peripheral blood apheresis was correlated with the yield of CD3+ T cells (p < 0.001) and CD4+ T cells (p = 0.001). The peripheral blood monocyte count before marrow harvest predicted the monocyte dose (p = 0.002). The results suggested that older and overweight donors should not be chosen. The monocyte and lymphocyte counts before harvest could predict the yield of immune cells in allografts. © 2015 AABB.

Essential trace elements and antioxidant status in relation to severity of HIV in Nigerian patients.

PubMed

Olaniyi, J A; Arinola, O G

2007-01-01

This study was designed to determine the plasma levels of some antioxidants and trace elements in three severity groups of HIV patients compared with non-HIV-infected controls. The plasma levels of antioxidants (total antioxidant, albumin, bilirubin and uric acid) and trace elements (Mg, Fe, Zn, Mn, Cu, Cr, Cd and Se) were estimated spectrophotometrically in controls and patients with CD4 counts of <200; 200-499 and > or =500 cells/microl. Uric acid and Zn were significantly higher, while vitamin E and all the trace elements (except Zn) were significantly lower in HIV-infected patients compared to healthy controls. The highest level of uric acid was observed in those with CD4 counts of <200 cells/microl. All the trace elements (except Zn) were higher in HIV subjects with a CD4 count of 200-499 cells/microl compared to >500 cells/microl. Only uric acid and Zn showed significant correlation with CD4 count. Based on the results of this study, we recommend routine assessment and appropriate supplementation of antioxidants/trace elements in HIV subjects. This supplementation is hoped to strengthen the immune system and reduce the adverse consequences of HIV- related oxidative stress. Copyright 2007 S. Karger AG, Basel.

Therapeutic DNA vaccination of vertically HIV-infected children: report of the first pediatric randomised trial (PEDVAC).

PubMed

Palma, Paolo; Romiti, Maria Luisa; Montesano, Carla; Santilli, Veronica; Mora, Nadia; Aquilani, Angela; Dispinseri, Stefania; Tchidjou, Hyppolite K; Montano, Marco; Eriksson, Lars E; Baldassari, Stefania; Bernardi, Stefania; Scarlatti, Gabriella; Wahren, Britta; Rossi, Paolo

2013-01-01

Twenty vertically HIV-infected children, 6-16 years of age, with stable viral load control and CD4+ values above 400 cells/mm(3). Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. clinicaltrialsregister.eu _2007-002359-18IT.

Therapeutic DNA Vaccination of Vertically HIV-Infected Children: Report of the First Pediatric Randomised Trial (PEDVAC)

PubMed Central

Palma, Paolo; Romiti, Maria Luisa; Montesano, Carla; Santilli, Veronica; Mora, Nadia; Aquilani, Angela; Dispinseri, Stefania; Tchidjou, Hyppolite K.; Montano, Marco; Eriksson, Lars E.; Baldassari, Stefania; Bernardi, Stefania; Scarlatti, Gabriella

2013-01-01

Subjects Twenty vertically HIV-infected children, 6–16 years of age, with stable viral load control and CD4+ values above 400 cells/mm3. Intervention Ten subjects continued their ongoing antiretroviral treatment (ART, Group A) and 10 were immunized with a HIV-DNA vaccine in addition to their previous therapy (ART and vaccine, Group B). The genetic vaccine represented HIV-1 subtypes A, B and C, encoded Env, Rev, Gag and RT and had no additional adjuvant. Immunizations took place at weeks 0, 4 and 12, with a boosting dose at week 36. Monitoring was performed until week 60 and extended to week 96. Results Safety data showed good tolerance of the vaccine. Adherence to ART remained high and persistent during the study and did not differ significantly between controls and vaccinees. Neither group experienced either virological failure or a decline of CD4+ counts from baseline. Higher HIV-specific cellular immune responses were noted transiently to Gag but not to other components of the vaccine. Lymphoproliferative responses to a virion antigen HIV-1 MN were higher in the vaccinees than in the controls (p = 0.047), whereas differences in reactivity to clade-specific Gag p24, RT or Env did not reach significance. Compared to baseline, the percentage of HIV-specific CD8+ lymphocytes releasing perforin in the Group B was higher after the vaccination schedule had been completed (p = 0.031). No increased CD8+ perforin levels were observed in control Group A. Conclusions The present study demonstrates the feasibility, safety and moderate immunogenicity of genetic vaccination in vertically HIV-infected children, paving the way for amplified immunotherapeutic approaches in the pediatric population. Trial registration clinicaltrialsregister.eu _2007-002359-18 IT PMID:24312194

Oral microflora and their relation to risk factors in HIV+ patients with oropharyngeal candidiasis.

PubMed

Sharifzadeh, A; Khosravi, A R; Shokri, H; Asadi Jamnani, F; Hajiabdolbaghi, M; Ashrafi Tamami, I

2013-06-01

The purpose of this study was to determine the prevalence of oral microflora and association of oral candidiasis and multiple risk factors in HIV(+) patients. The present study included 100 HIV-infected patients participated in Imam Khomeini Hospital, Tehran, Iran for Oropharyngeal candidiasis (OPC) and HIV. We assessed the presence or absence of OPC, and samples were obtained from the oral cavity and direct microscopic examination, gram staining and culture on standard microbiological media were performed in all patients. CD4(+) cell count/CD4(+) percentage were also calculated. The demographic characteristics showed that the patients had a mean age of 32.3 years old, 78% male and 22% female. Patients belonging to 'O(+)' blood group (27%) were more prone to develop OPC. A total of 460 bacterial colonies were obtained and Streptococcus mutans (15.4%) was the most frequently isolated species in the HIV(+) patients, followed by Staphylococcus epidermidis (12.8%) and Corynebacterium (8.7%). In addition, 254 yeasts (from four different genera) were isolated from the patient under study. Candida species (94.4%) were the most frequently obtained genera, followed by Saccharomyces (2.4%), Kluyveromyces and Cryptococcus (1.6% for both) species. Candida albicans (37.2%) was the most common species isolated from HIV(+) patients with OPC and its frequency was significantly higher than that of other Candida species (P<0.05). Candida glabrata, C. dubliniensis, C. tropicalis, C. parapsilosis, C. krusei, C. lusitaniae, C. guilliermondii and C. norvegensis were also identified. Forty percent of the patients had angular cheilitis as the most frequent clinical variant. The mean CD4(+) cell counts were 154.5 cells/μL, with a range of 8 to 611 cells/μL. Thirty percent patients had a CD4(+) cell count between 101 and 200 cells/μL (28.7% of total yeasts isolated). Yeast and bacteria counts did not differ statistically among HIV(+) patients' subgroups with different levels of CD4(+) cells counts. Our results showed that yeasts of the genus Candida were isolated at a comparable rate from the oral cavity of HIV(+) patients and there was no significant difference of the variables CD4(+) cell count and yeast counts. The findings of this study would be helpful in any further study, which, if done prospectively on a large cohort, can be confirmatory. Copyright © 2013. Published by Elsevier SAS.

Regular monitoring of cytomegalovirus (CMV)-specific cell-mediated immunity in intermediate-risk kidney transplant recipients: predictive value of the immediate post-transplant assessment.

PubMed

Fernández-Ruiz, Mario; Giménez, Estela; Vinuesa, Víctor; Ruiz-Merlo, Tamara; Parra, Patricia; Amat, Paula; Montejo, Miguel; Paez-Vega, Aurora; Cantisán, Sara; Torre-Cisneros, Julián; Fortún, Jesús; Andrés, Amado; San Juan, Rafael; López-Medrano, Francisco; Navarro, David; María Aguado, José

2018-05-24

Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-center designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicenter cohort of intermediate-risk kidney transplant (KT) recipients. We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction preemptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4 + and CD8 + T-cells were enumerated through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and IE-1 peptides (mean of 6 measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T-cells were calculated at baseline and day 15. Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8 + T-cell count <1.0 cells/μL had higher risk of CMV events (adjusted hazard ratio [aHR]: 2.84; P-value = 0.054). When the CMI assessment was performed at the immediate post-transplant period (day 15), the presence of <2.0 CD8 + T-cells/μL (aHR: 2.18; P-value = 0.034) or <1.0 CD4 + T-cells/μL (aHR: 2.43; P-value = 0.016) also predicted the subsequent development of CMV event. In addition, lower counts of CMV-specific CD4 + (but not CD8 + ) T-cells at days 60 and 180 were associated with a higher incidence of late-onset events. Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

New-onset type 2 diabetes mellitus among patients receiving HIV care at Newlands Clinic, Harare, Zimbabwe: retrospective cohort analysis.

PubMed

Chimbetete, Cleophas; Mugglin, Catrina; Shamu, Tinei; Kalesan, Bindu; Bertisch, Barbara; Egger, Matthias; Keiser, Olivia

2017-07-01

To assess the incidence and associated factors of Type 2 Diabetes Mellitus (T2DM) among people living with HIV (PLHIV) in Zimbabwe. We analysed data of all HIV-infected patients older than 16 years who attended Newlands Clinic between March 1, 2004 and April 29, 2015. The clinic considers patients whose random blood sugar is higher than 11.1 mmol/l and which is confirmed by a fasting blood sugar higher than 7.0 mmol/l to have T2DM. T2DM is also diagnosed in symptomatic patients who have a RBS >11.0 mmol/l. Risk factors for developing T2DM were identified using Cox proportional hazard models adjusted for confounding. Missing baseline BMI data were multiply imputed. Results are presented as adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI). Data for 4,110 participants were included: 67.2% were women; median age was 37 (IQR: 31-43) years. Median baseline CD4 count was 197 (IQR: 95-337) cells/mm 3 . The proportion of participants with hypertension at baseline was 15.5% (n=638). Over a median follow-up time of 4.7 (IQR: 2.1-7.2) years, 57 patients developed T2DM; the overall incidence rate was 2.8 (95% CI: 2.1-3.6) per 1000 person-years of follow-up. Exposure to PIs was associated with T2DM (HR: 1.80, 95% CI: 1.04-3.09). In the multivariable analysis, obesity (BMI>30 kg/m 2 ) (aHR=2.26, 95% CI: 1.17-4.36), age >40 years (aHR=2.16, 95% CI: 1.22-3.83) and male gender, (aHR=2.13, 95% CI: 1.22-3.72) were independently associated with the risk of T2DM. HIV-related factors (baseline CD4 cell count and baseline WHO clinical stage) were not independent risk factors for developing T2DM. Although the incidence of T2DM in this HIV cohort was lower than that has been observed in others, our results show that risk factors for developing T2DM among HIV-infected people are similar to those of the general population. HIV-infected patients in sub-Saharan Africa need a comprehensive approach to care that includes better health services for prevention, early detection and treatment of chronic diseases especially among the elderly and obese. © 2017 John Wiley & Sons Ltd.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.

PubMed

Lundgren, Jens D; Babiker, Abdel G; Gordin, Fred; Emery, Sean; Grund, Birgit; Sharma, Shweta; Avihingsanon, Anchalee; Cooper, David A; Fätkenheuer, Gerd; Llibre, Josep M; Molina, Jean-Michel; Munderi, Paula; Schechter, Mauro; Wood, Robin; Klingman, Karin L; Collins, Simon; Lane, H Clifford; Phillips, Andrew N; Neaton, James D

2015-08-27

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

Value of HIV patients with regular follow-up as in-house internal controls of flow cytometry measurement of lymphocyte subsets.

PubMed

de Carvalho Bittencourt, Marcelo; Kohler, Chantal; Henard, Sandrine; Rabaud, Christian; Béné, Marie C; Faure, Gilbert C

2013-07-08

Background. Quality assessment in flow cytometry cannot obey the same rules as those applicable to the measurement of chemical analytes. However, regular follow-up of known patients may provide a robust in-house control of cell subsets evaluation. Methods. Sequential blood samples assessed for 32 HIV patients over several years and showing good stability were retrospectively assessed to establish coefficient of variations of the percentages of CD3+, CD4+, CD8+ cells and CD4+ absolute counts. Results. Mean relative standard variations for the whole cohort were of 0.04, 0.14, 0.08 and 0.18 for CD3%, CD4% CD8% and CD4 absolute counts respectively. Discussion. In-house follow up of regularly checked compliant patients is a good alternative to traditional and costly repeatability and reproducibility studies for the validation of routine flow cytometry. © 2013 Clinical Cytometry Society. Copyright © 2013 Clinical Cytometry Society.

Compartmentalized Cytomegalovirus Replication and Transmission in the Setting of Maternal HIV-1 Infection

PubMed Central

Slyker, Jennifer; Farquhar, Carey; Atkinson, Claire; Ásbjörnsdóttir, Kristjana; Roxby, Alison; Drake, Alison; Kiarie, James; Wald, Anna; Boeckh, Michael; Richardson, Barbra; Odem-Davis, Katherine; John-Stewart, Grace; Emery, Vincent

2014-01-01

Background. Cytomegalovirus (CMV) infection is associated with adverse outcomes in human immunodeficiency virus (HIV)–exposed infants. Determinants of vertical CMV transmission in the setting of maternal HIV-1 infection are not well-defined. Methods. CMV and HIV-1 levels were measured in plasma, cervical secretions, and breast milk of 147 HIV-1–infected women to define correlates of maternal CMV replication and infant CMV acquisition. Results. Although few women had detectable CMV in plasma (4.8%), the majority had detectable CMV DNA in cervical secretions (66%) and breast milk (99%). There was a strong association between cervical CMV detection during pregnancy and later breast milk levels (β = 0.47; P = .005). Plasma HIV-1 level and CD4 counts were associated with CMV in the cervix and breast milk. However HIV-1 levels within the cervix and breast milk were not associated with CMV within these compartments. Maternal breast milk CMV levels (hazard ratio [HR], 1.4; P = .003) and maternal CD4 < 450 cells/mm3 (HR, 1.8; P = .008) were independently associated with infant CMV acquisition; each log10 increase in breast milk CMV was associated with a 40% increase in infant infection. The breast milk CMV level required to attain a 50% probability of CMV transmission increased with higher maternal CD4 counts, increasing from 3.55 log10 CMV DNA copies/mL at a CD4 count of 350 cells/mm3 to 5.50 log10 CMV DNA copies/mL at a CD4 count of 1000 cells/mm3. Conclusions. Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission. PMID:24192386

Trends in and correlates of CD4+ cell count at antiretroviral therapy initiation after changes in national ART guidelines in Rwanda

PubMed Central

Mutimura, Eugene; Addison, Diane; Anastos, Kathryn; Hoover, Donald; Dusingize, Jean Claude; Karenzie, Ben; Izimukwiye, Isabelle; Mutesa, Leo; Nsanzimana, Sabin; Nashi, Denis

2015-01-01

Background Initiation of antiretroviral therapy (ART) in the advanced stages of HIV infection remains a major challenge in sub-Saharan Africa. This study was conducted to better understand barriers and enablers to timely ART initiation in Rwanda where ART coverage is high and national ART eligibility guidelines first expanded in 2007–2008. Methods Using data on 6326 patients (≥15 years) at five Rwandan clinics, we assessed trends and correlates of CD4+ cell count at ART initiation and the proportion initiating ART with advanced HIV disease (CD4+ <200 cells/µl or WHO stage IV). Results Out of 6326 patients, 4486 enrolling in HIV care initiated ART with median CD4+ cell count of 211 cells/µl [interquartile range: 131–300]. Median CD4+ cell counts at ART initiation increased from 183 cells/µl in 2007 to 293 cells/µl in 2011–2012, and the proportion with advanced HIV disease decreased from 66.2 to 29.4%. Factors associated with a higher odds of advanced HIV disease at ART initiation were male sex [adjusted odds ratios (AOR) = 1.7; 95% confidence interval (CI): 1.3–2.1] and older age (AOR46–55+ vs. <25 = 2.3; 95% CI: 1.2–4.3). Among those initiating ART more than 1 year after enrollment in care, those who had a gap in care of 12 or more months prior to ART initiation had higher odds of advanced HIV disease (AOR = 5.2; 95% CI: 1.2–21.1). Conclusion Marked improvements in the median CD4+ cell count at ART initiation and proportion initiating ART with advanced HIV disease were observed following the expansion of ART eligibility criteria in Rwanda. However, sex disparities in late treatment initiation persisted through 2011–2012, and appeared to be driven by later diagnosis and/or delayed linkage to care among men. PMID:25562492

Synergistic immunosuppression by candida in HIV infection: a cytokine based analysis.

PubMed

Bajaj, J S; Singh, A; Aggarwal, S K; Chattopadhya, D; Baveja, U K

2000-03-01

Candida is a common opportunistic pathogen in HIV infection and is regarded a signal infection for progression to AIDS. Cytokine imbalances between Th1/Th2 groups have been described in both candida and HIV infections. A study was undertaken to assess the role of candida in furthering immunosuppression in HIV infection based on cytokine levels and CD4 cell counts. 30 Indian subjects were enrolled; 10 HIV positive patients with and 10 without mucosal candidiasis and 10 age matched controls. Th1 cytokines; interleukin (IL) 2, IL 12 and interferon (IFN) gamma, Th2 cytokines; IL 4, IL 6, IL 10 and tumor necrosis factor (TNF) alpha with CD 4 cell counts were estimated using ELISA in all subjects. CD4 cell counts were reduced in both patient groups as compared to controls; significantly more in patients with both HIV and candida infections. There was a decrease in Th1 cytokine levels in all patients; lower levels of Th1 cytokines were seen in patients with both infections. Among the Th2 cytokines, there was a significant increase in the levels of IL 6, IL 10 and TNF alpha in both patient groups; IL 10 and TNF alpha values were significantly raised in patients with dual HIV and candida infections as compared to the other patients. There was no difference in IL 4 values across the subject groups. A positive correlation between CD4 cell counts and Th1 cytokine levels and a negative correlation with Th2 cytokines were noted; these were stronger in patients with both HIV and candidiasis. Thus, there was a Th1/Th2 cytokine imbalance with CD4 cell count reduction in all HIV infected patients, which was more pronounced in patients with both infections. It can be concluded that, owing to the depressed CD4 cell count and Th1 response and increased Th2 cytokines in patients with both candidiasis and HIV as compared to patients with only HIV candidiasis may have a synergistic immunosuppressive effect with HIV in patients with dual infections.

Occupational exposure to formaldehyde and alterations in lymphocyte subsets

PubMed Central

Hosgood, H. Dean; Zhang, Luoping; Tang, Xiaojiang; Vermeulen, Roel; Hao, Zhenyue; Shen, Min; Qiu, Chuangyi; Ge, Yichen; Hua, Ming; Ji, Zhiying; Li, Senhua; Xiong, Jun; Reiss, Boris; Liu, Songwang; Xin, Kerry X.; Azuma, Mariko; Xie, Yuxuan; Freeman, Laura Beane; Ruan, Xiaolin; Guo, Weihong; Galvan, Noe; Blair, Aaron; Li, Laiyu; Huang, Hanlin; Smith, Martyn T.; Rothman, Nathaniel; Lan, Qing

2012-01-01

Background Formaldehyde is used in many occupational settings, most notably in manufacturing, health care, and embalming. Formaldehyde has been classified as a human carcinogen, but its mechanism of action remains uncertain. Methods We carried out a cross-sectional study of 43 formaldehyde exposed-workers and 51 unexposed age and sex-matched controls in Guangdong, China to study formaldehyde’s early biologic effects. To follow-up our previous report that the total lymphocyte count was decreased in formaldehyde-exposed workers compared to controls, we evaluated each major lymphocyte subset (i.e., CD4+ T cells, CD8+ T cells, natural killer (NK) cells, and B cells) and T cell lymphocyte subset (CD4+ naïve and memory T cells, CD8+ naïve and memory T cells, and regulatory T cells). Linear regression of each subset was used to test for differences between exposed workers and controls, adjusting for potential confounders. Results Total NK cell and T cell counts were about 24% (p=0.037) and 16% (p=0.0042) lower, respectively, among exposed workers. Among certain T cell subsets, decreased counts among exposed workers were observed for CD8+ T cells (p=0.026), CD8+ effector memory T cells (p=0.018), and regulatory T cells (CD4+FoxP3+: p=0.04; CD25+FoxP3+: p=0.008). Conclusions Formaldehyde exposed-workers experienced decreased counts of NK cells, regulatory T cells, and CD8+ effector memory T cells; however, due to the small sample size these findings need to be confirmed in larger studies. PMID:22767408

Weight Gain: A Possible Side Effect of All Antiretrovirals

PubMed Central

Ricci, Elena; Menzaghi, Barbara; Orofino, Giancarlo; Passerini, Simone; Madeddu, Giordano; Martinelli, Canio Vito; De Socio, Giuseppe Vittorio; Squillace, Nicola; Rusconi, Stefano; Bonfanti, Paolo; Di Biagio, Antonio; Quirino, T; Bonfanti, P; Ricci, E; Bellacosa, C; Maggi, P; Calza, L; Abeli, C; Menzaghi, B; Celesia, B M; Grosso, C; Stagno, A; Vichi, F; Mazzotta, F; Martinelli, C; Penco, G; Cassola, G; Di Biagio, A; Taramasso, L; Nicolini, L A; Dentone, C; Molteni, C; Palvarini, L; Scalzini, A; Carenzi, L; Rizzardini, G; Valsecchi, L; Cordier, L; Rusconi, S; Colombo, V; Galli, M; Franzetti, M; De Socio, G V; Mazzotta, E; Parruti, G; Madeddu, G; Bagella, P; S. Mura, M; Libertone, R; Antinori, A; Di Giambenedetto, S; Orofino, G; Guastavigna, M; Caramell, P

2017-01-01

Abstract Weight gain and body mass index (BMI) increase are central issues in patients living with HIV who need to minimize the risk of metabolic disease. Information collected through the SCOLTA cohort revealed significant 1-year BMI increase in patients treated with dolutegravir (P = .004), raltegravir (P = .0004), elvitegravir (P = .004), darunavir (P = .0006), and rilpivirine (P = .029). BMI gain correlated with low baseline BMI (P = .002) and older age (P = .0007) in Centers for Disease Control and Prevention stages A/B, with lower BMI (P = .005) and CD4+ T-cell count (P = .007) at enrollment in stage C. PMID:29255735

Serum levels of antioxidant vitamins and mineral elements of human immunodeficiency virus positive subjects in Sokoto, Nigeria.

PubMed

Bilbis, Lawal S; Idowu, Dorcas B; Saidu, Yusuf; Lawal, Mansur; Njoku, Chibueze H

2010-01-01

Undernourishment and micronutrient deficiencies exacerbate immunosuppression, oxidative stress, acceleration of human immunodeficiency virus (HIV) replication and CD4 T-cell depletion in HIV-infected individuals. The current work reports the serum levels of antioxidant vitamins (vitamins A, C and E) and minerals (Zn, Fe, Cu) in 90 HIV positive subjects attending the Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto, Nigeria. The serum levels of the micronutrients were correlated with the CD4 count of the subjects. The results showed that the HIV positive subjects have significantly lower (P < 0.05) levels of vitamins A, C and E. Also, serum Zn, Fe, Cu and CD4 count were also significantly (P < 0.05) lower compared with the HIV negative subjects. Micronutrient deficiencies were more pronounced in HIV positive subjects with CD4 counts less than 200 cell/μl. The results based on age and sex showed no significant (P > 0.05) difference. Vitamins A, E and C and Zn and Fe showed positive correlation with CD4 count of the HIV positive subjects. The results suggest that the HIV subjects in the study area have lowered serum levels of antioxidant micronutrients and that the levels decrease with increase in the severity of the infection. These may increase the chances of the symptomatic and asymptomatic subjects progressing into full-blown Acquired Immunodeficiency Syndrome.

Quality of life in an Italian cohort of people living with HIV in the era of combined antiretroviral therapy (Evidence from I.A.N.U.A. study-investigation on antiretroviral therapy).

PubMed

Venturini, A; Cenderello, G; Di Biagio, A; Giannini, B; Ameri, M; Giacomini, M; Montefiori, M; Setti, M; Mazzarello, G; Merlano, C; Orcamo, P; Viscoli, C; Cassola, G

2017-11-01

The aims of this study were to assess the Health Related Quality of Life (HRQoL) of People Living with HIV/AIDS (PLWHA) who attend outpatient services in Genoa, Italy, and to evaluate the relationship between HRQoL and clinical factors, primarily: CD4+ cell count, viral load and HIV-Hepatitis C Virus (HCV) coinfection. A cross-sectional study was performed involving a sample of 943 consecutive patients. Firstly the EuroQol-Five Dimensions-Three Level (EQ-5D-3L) self-reported questionnaire was used to evaluate HRQoL, while socio-demographic information was collected using a separate self-administered questionnaire. Descriptive statistical analysis was then used to show the socio-demographic and clinical characteristics of the sample. Having characterized the sample, Pearson's correlation technique was used to assess the relationship between HRQoL and socio-demographic and clinical characteristics. Finally, multivariable linear regression was used to determine factors associated with HRQOL. The median EQ-Visual analogue scale (EQ-VAS) score was 75.4 (SD 18.4). We found statistically significant associations between the EQ-VAS score and age, coinfection with HCV+, education, other drugs taken over cART, hospitalization due to HIV and a CD4+ cell count <200 mm 3 compared with CD4+ cell count >500 mm 3 . Factors independently associated with lower HRQoL were: older age, coinfection with HCV+, other drugs used in addition to cART, hospitalization due to HIV and CD4+ cell count <200 mm 3 compared with CD4+ cell count >500 mm 3 .

Estimated Prevalence of Cryptococcus Antigenemia (CrAg) among HIV-Infected Adults with Advanced Immunosuppression in Namibia Justifies Routine Screening and Preemptive Treatment.

PubMed

Sawadogo, Souleymane; Makumbi, Boniface; Purfield, Anne; Ndjavera, Christophine; Mutandi, Gram; Maher, Andrew; Kaindjee-Tjituka, Francina; Kaplan, Jonathan E; Park, Benjamin J; Lowrance, David W

2016-01-01

Cryptococcal meningitis is common and associated with high mortality among HIV infected persons. The World Health Organization recommends that routine Cryptococcal antigen (CrAg) screening in ART-naïve adults with a CD4+ count <100 cells/μL followed by pre-emptive antifungal therapy for CrAg-positive patients be considered where CrAg prevalence is ≥3%. The prevalence of CrAg among HIV adults in Namibia is unknown. We estimated CrAg prevalence among HIV-infected adults receiving care in Namibia for the purpose of informing routine screening strategies. The study design was cross-sectional. De-identified plasma specimens collected for routine CD4+ testing from HIV-infected adults enrolled in HIV care at 181 public health facilities from November 2013 to January 2014 were identified at the national reference laboratory. Remnant plasma from specimens with CD4+ counts <200 cells/μL were sampled and tested for CrAg using the IMMY® Lateral Flow Assay. CrAg prevalence was estimated and assessed for associations with age, sex, and CD4+ count. A total of 825 specimens were tested for CrAg. The median (IQR) age of patients from whom specimens were collected was 38 (32-46) years, 45.9% were female and 62.9% of the specimens had CD4 <100 cells/μL. CrAg prevalence was 3.3% overall and 3.9% and 2.3% among samples with CD4+ counts of CD4+<100 cells/μL and 100-200 cells/μL, respectively. CrAg positivity was significantly higher among patients with CD4+ cells/μL < 50 (7.2%, P = 0.001) relative to those with CD4 cells/μL 50-200 (2.2%). This is the first study to estimate CrAg prevalence among HIV-infected patients in Namibia. CrAg prevalence of ≥3.0% among patients with CD4+<100 cells/μL justifies routine CrAg screening and preemptive treatment among HIV-infected in Namibia in line with WHO recommendations. Patients with CD4+<100 cells/μL have a significantly greater risk for CrAg positivity. Revised guidelines for ART in Namibia now recommend routine screening for CrAg.

Outcomes of human immunodeficiency virus-infected children after anti-retroviral therapy in Malaysia.

PubMed

Moy, Fong Siew; Fahey, Paul; Nik Yusoff, Nik K; Razali, Kamarul A; Nallusamy, Revathy

2015-02-01

To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART). Retrospective and prospective data collected through March 2009 from children in four different states in Malaysia enrolled in TREAT Asia's Pediatric HIV Observational Database were analysed. Of 347 children in the cohort, only 278 (80.1%) were commenced on ART. The median CD4 count and median age at baseline prior to ART was 272 cells/μL and 4.2 years (interquartile range (IQR): 1.4, 7.4 years), respectively. The median duration of follow-up was 3.7 years (IQR: 1.8, 6.0) with 32 deaths giving a crude mortality rate of 2.86 per 100 child-years. The mortality rate highest in the first 6 months of ART was 10.62 per 100 child-years and declined to 1.83 per 100 child-years thereafter. On univariate analyses, only baseline median CD4 percentage, weight for age z score, height for age z score and anaemia were significantly associated with mortality. Upon including all four of these predictors into a single multivariate model, only weight for age z score remained statistically significantly predictive of mortality. Children commenced on ART had high mortality in the first 6 months especially in those with low CD4 percentage, wasting and anaemia. Poor nutritional status is an important independent predictor of mortality in this study. Besides initiating ART therapy, nutritional support and intervention must receive the utmost attention. © 2014 The Authors. Journal of Paediatrics and Child Health © 2014 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

When to initiate highly active antiretroviral therapy in low-resource settings: the Moroccan experience.

PubMed

Loubiere, Sandrine; el Filal, Kamal Marhoum; Sodqi, Mustapha; Loundou, Anderson; Luchini, Stéphane; Cleary, Susan; Moatti, Jean-Paul; Himmich, Hakima

2008-01-01

The aim of this study was to assess the cost-effectiveness of HIV treatment alternatives - with and without highly active antiretroviral therapy (HAART) - within alternative strata based on the CD4+ T-cell count at the initiation of treatment in a low-resource setting. A retrospective observational study was conducted following 286 HIV-positive individuals admitted to the principal teaching hospital in Casablanca, Morocco, between 1995 and 2002. Patients were stratified by CD4+ T-cell count and regression models were fitted to determine risk of opportunistic infection. Data on healthcare resource use were derived from patient records and were evaluated from the hospital perspective. HAART led to a significant reduction in the number of HIV-related opportunistic infections (P<0.0001), extended survival (61.3 versus 55.2 months; P<0.0001) and reduced hospital stays (P<0.0001) in comparison with care in the absence of HAART. When medical care and drug costs were considered together, HAART was more costly than providing treatment for opportunistic infections. The incremental cost-effectiveness ratio was lower than gross domestic product (GDP) per capita for patients starting HAART with a CD4+ T-cell count <200 cells/mm3, but this increased to nearly three times GDP per capita when HAART was initiated at CD4+ T-cell counts above this threshold. HAART is more cost-effective than treating HIV-related opportunistic infections and, contrary to conclusions drawn in developed countries, HAART is more cost-effective when the CD4+ T-cell count drops to <200 cells/mm3.

Discontinuing Pneumocystis jirovecii Pneumonia Prophylaxis in HIV-Infected Patients With a CD4 Cell Count <200 cells/mm3.

PubMed

Sidhu, Vaninder K; Foisy, Michelle M; Hughes, Christine A

2015-12-01

To review the evidence for discontinuing primary and secondary Pneumocystis jirovecii pneumonia (PJP) prophylaxis in HIV-infected patients with a CD4 count <200 cells/mm(3). We conducted a literature search in MEDLINE, EMBASE, Cochrane Library, Google Scholar, and the International Aids Society Library (up to August 2015) using the following key search terms: Pneumocystis jirovecii, pneumonia, human immunodeficiency virus, primary prophylaxis, secondary prophylaxis, and discontinuation. All English-language studies that evaluated discontinuation of primary and/or secondary PJP prophylaxis in HIV-infected patients with CD4 count <200 cells/mm(3) were included. Five studies were identified, which varied in design, sample size, outcomes, and duration of follow-up. Three studies examined discontinuation of primary and secondary PJP prophylaxis; 1 study evaluated discontinuing primary PJP prophylaxis; and 1 study evaluated stopping secondary PJP prophylaxis. Two out of the 5 studies pooled data for all opportunistic infections. Overall, there was a low incidence of PJP among HIV-infected patients who discontinued primary PJP prophylaxis and were well controlled on antiretroviral therapy (ART). Discontinuation of primary PJP prophylaxis appears to be safe in patients on combination ART with a suppressed HIV viral load and a CD4 count >100 cells/mm(3). Additional data are needed to support the safety of discontinuing secondary PJP prophylaxis. Decisions to discontinue PJP prophylaxis in patients with a CD4 count <200 cells/mm(3) should be done on an individual patient basis, taking into consideration clinical factors, including ongoing adherence to ART. © The Author(s) 2015.

The role of donor characteristics and post-granulocyte colony-stimulating factor white blood cell counts in predicting the adverse events and yields of stem cell mobilization.

PubMed

Chen, Shu-Huey; Yang, Shang-Hsien; Chu, Sung-Chao; Su, Yu-Chieh; Chang, Chu-Yu; Chiu, Ya-Wen; Kao, Ruey-Ho; Li, Dian-Kun; Yang, Kuo-Liang; Wang, Tso-Fu

2011-05-01

Granulocyte colony-stimulating factor (G-CSF) is now widely used for stem cell mobilization. We evaluated the role of post-G-CSF white blood cell (WBC) counts and donor factors in predicting adverse events and yields associated with mobilization. WBC counts were determined at baseline, after the third and the fifth dose of G-CSF in 476 healthy donors. Donors with WBC ≥ 50 × 10(3)/μL post the third dose of G-CSF experienced more fatigue, myalgia/arthralgia, and chills, but final post-G-CSF CD34(+) cell counts were similar. Although the final CD34(+) cell count was higher in donors with WBC ≥ 50 × 10(3)/μL post the fifth G-CSF, the incidence of side effects was similar. Females more frequently experienced headache, nausea/anorexia, vomiting, fever, and lower final CD34(+) cell count than did males. Donors with body mass index (BMI) ≥ 25 showed higher incidences of sweat and insomnia as well as higher final CD34(+) cell counts. Donor receiving G-CSF ≥ 10 μg/kg tended to experience bone pain, headache and chills more frequently. Multivariate analysis indicated that female gender is an independent factor predictive of the occurrence of most side effects, except for ECOG > 1 and chills. Higher BMI was also an independent predictor for fatigue, myalgia/arthralgia, and sweat. Higher G-CSF dose was associated with bone pain, while the WBC count post the third G-CSF was associated with fatigue only. In addition, one donor in the study period did not complete the mobilization due to suspected anaphylactoid reaction. Observation for 1 h after the first injection of G-CSF is required to prevent complications from unpredictable side effects.

Immunoglobulin G (IgG) Subclass Distribution and IgG1 Avidity of Antibodies in Human Immunodeficiency Virus-Infected Individuals after Revaccination with Tetanus Toxoid

PubMed Central

Kroon, F. P.; van Tol, M. J. D.; Jol-van der Zijde, C. M.; van Furth, R.; van Dissel, J. T.

1999-01-01

In human immunodeficiency virus (HIV)-infected individuals the amount of antibodies formed after vaccination with T-cell-dependent recall antigens such as tetanus toxoid is proportional to the peripheral blood CD4+ T-lymphocyte counts. To investigate whether the immunoglobulin G (IgG) subclass distribution and avidity of the antibodies produced after vaccination are affected as well, we gave 13 HIV-infected adults with low CD4+ T-lymphocyte counts (<200 × 106/liter; group I), 11 HIV-infected adults with intermediate CD4+ T-lymphocyte counts (≥200 × 106/liter; group II), and 5 healthy controls booster immunizations with tetanus toxoid. The prevaccination antibody concentrations against tetanus toxoid were similar in the HIV-infected and healthy adults. After vaccination the total IgG and the IgG1 anti-tetanus toxoid antibody concentrations were significantly lower in group I than in group II and the controls. The avidity of the IgG1 anti-tetanus toxoid antibodies formed by HIV-infected adults was within the range for healthy controls, irrespective of their CD4+ T-lymphocyte counts. PMID:10225835

Comparative Peripheral Blood T Cells Analysis Between Adult Deceased Donor Liver Transplantation (DDLT) and Living Donor Liver Transplantation (LDLT).

PubMed

Kim, Jong Man; Kwon, Choon Hyuck David; Joh, Jae-Won; Choi, Gyu-Seong; Kang, Eun-Suk; Lee, Suk-Koo

2017-08-08

BACKGROUND T lymphocytes are an essential component of allograft rejection and tolerance. The aim of the present study was to analyze and compare the characteristics of T cell subsets in patients who underwent deceased donor liver transplantation (DDLT) versus living donor liver transplantation (LDLT). MATERIAL AND METHODS Between April 2013 and June 2014, 64 patients underwent adult liver transplantation. The distribution of peripheral blood T lymphocyte subsets before transplantation and at 4, 8, 12, and 24 weeks post-transplantation were monitored serially. RESULTS In the serial peripheral blood samples, the absolute CD3+ T cell counts in the LDLT group were higher than those in the DDLT group (p=0.037). The CD4+, CD8+, CD4/CD8, Vδ1, Vδ2, and γδ T cell counts did not change significantly over time in either group. The Vδ1/Vδ2 ratio was higher in patients with cytomegalovirus (CMV) infection than in patients without CMV infection (0.12 versus 0.26; p=0.033). The median absolute CD3+ and CD8+ T cell counts in patients with biopsy-proven acute rejection (BPAR) were 884 (range, 305-1,320) and 316 (range, 271-1,077), respectively, whereas they were 320 (range, 8-1,167) and 257 (range, 58-1,472) in patients without BPAR. The absolute CD3+ and CD8 T cell counts were higher in patients with BPAR than in patients without BPAR (p=0.007 and p=0.039, respectively). CONCLUSIONS With the exception of CD3+ T cells, T cell populations did not differ significantly between patients who received DDLT versus LDLT. In liver transplantation patients, CMV infection and BPAR were closely associated with T cell population changes.

Microfluidic differential immunocapture biochip for specific leukocyte counting

PubMed Central

Hassan, Umer; Watkins, Nicholas N; Reddy, Bobby; Damhorst, Gregory; Bashir, Rashid

2016-01-01

Enumerating specific cell types from whole blood can be very useful for research and diagnostic purposes—e.g., for counting of cD4 and cD8 t cells in HIV/aIDs diagnostics. We have developed a biosensor based on a differential immunocapture technology to enumerate specific cells in 30 min using 10 µl of blood. this paper provides a comprehensive stepwise protocol to replicate our biosensor for cD4 and cD8 cell counts. the biochip can also be adapted to enumerate other specific cell types such as somatic cells or cells from tissue or liquid biopsies. capture of other specific cells requires immobilization of their corresponding antibodies within the capture chamber. therefore, this protocol is useful for research into areas surrounding immunocapture-based biosensor development. the biosensor production requires 24 h, a one-time cell capture optimization takes 6–9 h, and the final cell counting experiment in a laboratory environment requires 30 min to complete. PMID:26963632

Effect of raltegravir on the total and unintegrated proviral HIV DNA during raltegravir-based HAART.

PubMed

Nicastri, Emanuele; Tommasi, Chiara; Abbate, Isabella; Bonora, Stefano; Tempestilli, Massimo; Bellagamba, Rita; Viscione, Magdalena; Rozera, Gabriella; Gallo, Anna L; Ivanovic, Jelena; Amendola, Alessandra; Pucillo, Leopoldo; Di Perri, Giovanni; Capobianchi, Maria R; Narciso, Pasquale

2011-01-01

Raltegravir is the first approved antiretroviral able to prevent HIV genome integration into the host chromosomes. The aim of the study is to test if raltegravir plasma concentrations can be associated with proviral DNA decline during raltegravir-based salvage therapy. A total of 33 multidrug-resistant HIV-infected patients were enrolled in a longitudinal open-label pilot study and completed a 24-week follow-up. The CD4(+) T-cell count, plasma viral load, proviral HIV DNA and two-long-terminal repeat (2-LTR) circular forms were assessed at baseline, day 14, 30, 60, 90 and 180. The raltegravir trough concentration (C (trough)) was measured by HPLC-ultraviolet and patients were divided into two groups according to the median raltegravir C (trough). The mean±SD values of baseline HIV RNA, CD4(+) T-cell count and HIV DNA were 4.4±0.82 log copies/ml, 256±177 cells/mm(3) , and 2,668±4,721 copies/10(6) peripheral blood mononuclear cells, respectively. Despite a transient increase of total DNA at week 2, a marked proviral DNA decay (P=0.01) with an increase of the 2-LTR unintegrated/total DNA ratio (P=0.06) over time was observed. At univariate analysis, no correlation between raltegravir C(trough) and classical virological parameters was observed. Nevertheless, the decay of proviral HIV DNA was more pronounced in patients displaying C(trough)<158 ng/ml with respect to those with C(trough)>158 ng/ml (P=0.046). Successful raltegravir-based therapy produces a significant decline in proviral DNA and is associated with an increase of the unintegrated/total DNA ratio. Further studies are necessary to define the possible role of pharmacokinetic raltegravir monitoring and the biological meaning of unintegrated proviral DNA. © 2011 International Medical Press

Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT).

PubMed

Pett, S L; Carey, C; Lin, E; Wentworth, D; Lazovski, J; Miró, J M; Gordin, F; Angus, B; Rodriguez-Barradas, M; Rubio, R; Tambussi, G; Cooper, D A; Emery, S

2011-04-01

Bacterial pneumonia still contributes to morbidity/mortality in HIV infection despite effective combination antiretroviral therapy (cART). Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT), a trial of intermittent recombinant interleukin-2 (rIL-2) with cART vs. cART alone (control arm) in HIV-infected adults with CD4 counts ≥300cells/μL, offered the opportunity to explore associations between bacterial pneumonia and rIL-2, a cytokine that increases the risk of some bacterial infections. Baseline and time-updated factors associated with first-episode pneumonia on study were analysed using multivariate proportional hazards regression models. Information on smoking/pneumococcal vaccination history was not collected. IL-2 cycling was most intense in years 1-2. Over ≈7 years, 93 IL-2 [rate 0.67/100 person-years (PY)] and 86 control (rate 0.63/100 PY) patients experienced a pneumonia event [hazard ratio (HR) 1.06; 95% confidence interval (CI) 0.79, 1.42; P=0.68]. Median CD4 counts prior to pneumonia were 570cells/μL (IL-2 arm) and 463cells/μL (control arm). Baseline risks for bacterial pneumonia included older age, injecting drug use, detectable HIV viral load (VL) and previous recurrent pneumonia; Asian ethnicity was associated with decreased risk. Higher proximal VL (HR for 1 log(10) higher VL 1.28; 95% CI 1.11, 1.47; P<0.001) was associated with increased risk; higher CD4 count prior to the event (HR per 100 cells/μL higher 0.94; 95% CI 0.89, 1.0; P=0.04) decreased risk. Compared with controls, the hazard for a pneumonia event was higher if rIL-2 was received <180 days previously (HR 1.66; 95% CI 1.07, 2.60; P=0.02) vs.≥180 days previously (HR 0.98; 95% CI 0.70, 1.37; P=0.9). Compared with the control group, pneumonia risk in the IL-2 arm decreased over time, with HRs of 1.41, 1.71, 1.16, 0.62 and 0.84 in years 1, 2, 3-4, 5-6 and 7, respectively. Bacterial pneumonia rates in cART-treated adults with moderate immunodeficiency are high. The mechanism of the association between bacterial pneumonia and recent IL-2 receipt and/or detectable HIV viraemia warrants further exploration. © 2010 British HIV Association.

Nutritional status and CD4 cell counts in patients with HIV/AIDS receiving antiretroviral therapy.

PubMed

Santos, Ana Célia Oliveira dos; Almeida, Ana Maria Rampeloti

2013-01-01

Even with current highly active antiretroviral therapy, individuals with AIDS continue to exhibit important nutritional deficits and reduced levels of albumin and hemoglobin, which may be directly related to their cluster of differentiation 4 (CD4) cell counts. The aim of this study was to characterize the nutritional status of individuals with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and relate the findings to the albumin level, hemoglobin level and CD4 cell count. Patients over 20 years of age with AIDS who were hospitalized in a university hospital and were receiving antiretroviral therapy were studied with regard to clinical, anthropometric, biochemical and sociodemographic characteristics. Body mass index, percentage of weight loss, arm circumference, triceps skinfold and arm muscle circumference were analyzed. Data on albumin, hemoglobin, hematocrit and CD4 cell count were obtained from patient charts. Statistical analysis was performed using Fisher's exact test, Student's t-test for independent variables and the Mann-Whitney U-test. The level of significance was set to 0.05 (α = 5%). Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) 17.0 software for Windows. Of the 50 patients evaluated, 70% were male. The prevalence of malnutrition was higher when the definition was based on arm circumference and triceps skinfold measurement. The concentrations of all biochemical variables were significantly lower among patients with a body mass index of less than 18.5kg/m2. The CD4 cell count, albumin, hemoglobin and hematocrit anthropometric measures were directly related to each other. These findings underscore the importance of nutritional follow-up for underweight patients with AIDS, as nutritional status proved to be related to important biochemical alterations.

Invasive cervical cancer risk among HIV-infected women: A North American multi-cohort collaboration prospective study

PubMed Central

Abraham, Alison G; Strickler, Howard D; Jing, Yuezhou; Gange, Stephen J; Sterling, Timothy R; Silverberg, Michael; Saag, Michael; Rourke, Sean; Rachlis, Anita; Napravnik, Sonia; Moore, Richard D; Klein, Marina; Kitahata, Mari; Kirk, Greg; Hogg, Robert; Hessol, Nancy A; Goedert, James J; Gill, M John; Gebo, Kelly; Eron, Joseph J; Engels, Eric A; Dubrow, Robert; Crane, Heidi M; Brooks, John T; Bosch, Ronald; D’Souza, Gypsyamber

2013-01-01

Objective HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women. Methods Data were obtained from HIV-infected and -uninfected female participants in the NA-ACCORD with no history of ICC at enrollment. Participants were followed from study entry or January, 1996 through ICC, loss-to follow-up or December, 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios (SIR). All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction. Results A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years (pys) of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 pys, respectively). HIV-infected women with baseline CD4+ T-cells of ≥ 350, 200–349 and <200 cells/uL had a 2.3-times, 3.0-times and 7.7-times increase in ICC incidence, respectively, compared with HIV-uninfected women (Ptrend =0.001). Of the 17 HIV-infected cases, medical records for the 5 years prior to diagnosis showed that 6 had no documented screening, 5 had screening with low grade or normal results, and 6 had high-grade results. Conclusions This study found elevated incidence of ICC in HIV-infected compared to -uninfected women, and these rates increased with immunosuppression. PMID:23254153

Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults.

PubMed

Marzolini, Catia; Sabin, Caroline; Raffi, François; Siccardi, Marco; Mussini, Cristina; Launay, Odile; Burger, David; Roca, Bernardino; Fehr, Jan; Bonora, Stefano; Mocroft, Amanda; Obel, Niels; Dauchy, Frederic-Antoine; Zangerle, Robert; Gogos, Charalambos; Gianotti, Nicola; Ammassari, Adriana; Torti, Carlo; Ghosn, Jade; Chêne, Genevieve; Grarup, Jesper; Battegay, Manuel

2015-01-14

The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. Observational European cohort collaboration study. Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95). The study included 19,968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.

Increased naive CD4+ and B lymphocyte subsets are associated with body mass loss and drive relative lymphocytosis in anorexia nervosa patients.

PubMed

Elegido, Ana; Graell, Montserrat; Andrés, Patricia; Gheorghe, Alina; Marcos, Ascensión; Nova, Esther

2017-03-01

Anorexia nervosa (AN) is an atypical form of malnutrition with peculiar changes in the immune system. We hypothesized that different lymphocyte subsets are differentially affected by malnutrition in AN, and thus, our aim was to investigate the influence of body mass loss on the variability of lymphocyte subsets in AN patients. A group of 66 adolescent female patients, aged 12-17 years, referred for their first episode of either AN or feeding or eating disorders not elsewhere classified were studied upon admission (46 AN-restricting subtype, 11 AN-binge/purging subtype, and 9 feeding or eating disorders not elsewhere classified). Ninety healthy adolescents served as controls. White blood cells and lymphocyte subsets were analyzed by flow cytometry. Relationships with the body mass index (BMI) z score were assessed in linear models adjusted by diagnostic subtype and age. Leukocyte numbers were lower in AN patients than in controls, and relative lymphocytosis was observed in AN-restricting subtype. Lower CD8 + , NK, and memory CD8 + counts were found in eating disorder patients compared with controls. No differences were found for CD4 + counts or naive and memory CD4 + subsets between the groups. Negative associations between lymphocyte percentage and the BMI z score, as well as between the B cell counts, naive CD4 + percentage and counts, and the BMI z score, were found. In conclusion, increased naive CD4 + and B lymphocyte subsets associated with body mass loss drive the relative lymphocytosis observed in AN patients, which reflects an adaptive mechanism to preserve the adaptive immune response. Copyright © 2017 Elsevier Inc. All rights reserved.

Varicella Zoster Virus Necrotizing Retinitis in Two Patients with Idiopathic CD4 Lymphocytopenia.

PubMed

Gupta, Meenakashi; Jardeleza, Maria Stephanie R; Kim, Ivana; Durand, Marlene L; Kim, Leo; Lobo, Ann-Marie

2016-10-01

Progressive outer retinal necrosis (PORN) associated with varicella zoster virus (VZV) is usually diagnosed in HIV positive or immunosuppressed patients. We report two cases of immunocompetent patients with necrotizing viral retinitis found to have idiopathic CD4 lymphocytopenia. Clinical presentation, examination, imaging, and laboratory testing of two patients with VZV retinitis are presented. An HIV negative patient with history of herpes zoster presented with rapid loss of vision and examination consistent with PORN. PCR testing confirmed VZV. Lymphocytopenia was noted with a CD4 count of 25/mm(3). A second HIV negative patient presented with blurred vision and lid swelling and was found to have peripheral VZV retinitis confirmed by PCR. Laboratory workup revealed lymphocytopenia with a CD4 count of 133/mm(3). VZV necrotizing retinitis classic for PORN can occur in HIV negative patients. Idiopathic CD4 lymphocytopenia should be considered healthy patients who develop ocular infections seen in the immunocompromised.

Shamba Maisha: A pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients

PubMed Central

2010-01-01

Background HIV/AIDS negatively impacts poverty alleviation and food security, which reciprocally hinder the rapid scale up and effectiveness of HIV care programs. Nyanza province has the highest HIV prevalence (15.3%), and is the third highest contributor (2.4 million people) to rural poverty in Kenya. Thus, we tested the feasibility of providing a micro-irrigation pump to HIV-positive farmers in order to evaluate its impact on health and economic advancement among HIV-positive patients and their families. Methods Thirty HIV-positive patients enrolled in the Family AIDS Care and Education Services (FACES) program in Kisumu, Kenya were provided a micro-financed loan to receive an irrigation pump and farming guidance from KickStart, the developer of the pump. Economic data, CD4 counts, household health and loan repayment history were collected 12 months after the pumps were distributed. Results Mean annual family income increased by $1,332 over baseline. CD4 counts did not change significantly. Though income increased, only three (10%) participants had paid off more than a quarter of the loan. Conclusions We demonstrated the feasibility of an income-generating micro-irrigation intervention among HIV-positive patients and the collection of health and economic data. While family income improved significantly, loan repayment rates were low- likely complicated by the drought that occurred in Kenya during the intervention period. PMID:20459841

Shamba Maisha: a pilot study assessing impacts of a micro-irrigation intervention on the health and economic wellbeing of HIV patients.

PubMed

Pandit, Jay A; Sirotin, Nicole; Tittle, Robin; Onjolo, Elijah; Bukusi, Elizabeth A; Cohen, Craig R

2010-05-11

HIV/AIDS negatively impacts poverty alleviation and food security, which reciprocally hinder the rapid scale up and effectiveness of HIV care programs. Nyanza province has the highest HIV prevalence (15.3%), and is the third highest contributor (2.4 million people) to rural poverty in Kenya. Thus, we tested the feasibility of providing a micro-irrigation pump to HIV-positive farmers in order to evaluate its impact on health and economic advancement among HIV-positive patients and their families. Thirty HIV-positive patients enrolled in the Family AIDS Care and Education Services (FACES) program in Kisumu, Kenya were provided a micro-financed loan to receive an irrigation pump and farming guidance from KickStart, the developer of the pump. Economic data, CD4 counts, household health and loan repayment history were collected 12 months after the pumps were distributed. Mean annual family income increased by $1,332 over baseline. CD4 counts did not change significantly. Though income increased, only three (10%) participants had paid off more than a quarter of the loan. We demonstrated the feasibility of an income-generating micro-irrigation intervention among HIV-positive patients and the collection of health and economic data. While family income improved significantly, loan repayment rates were low- likely complicated by the drought that occurred in Kenya during the intervention period.

Distinct kinetics in the frequency of peripheral CD4+ T cells in patients with ulcerative colitis experiencing a flare during treatment with mesalazine or with a herbal preparation of myrrh, chamomile, and coffee charcoal.

PubMed

Langhorst, Jost; Frede, Annika; Knott, Markus; Pastille, Eva; Buer, Jan; Dobos, Gustav J; Westendorf, Astrid M

2014-01-01

We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25med effector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. EU Clinical Trials Register 2007-007928-18/DE.

Distinct Kinetics in the Frequency of Peripheral CD4+ T Cells in Patients with Ulcerative Colitis Experiencing a Flare during Treatment with Mesalazine or with a Herbal Preparation of Myrrh, Chamomile, and Coffee Charcoal

PubMed Central

Langhorst, Jost; Frede, Annika; Knott, Markus; Pastille, Eva; Buer, Jan; Dobos, Gustav J.; Westendorf, Astrid M.

2014-01-01

Background We found the first evidence of the efficacy of a herbal treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the herbal treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. Aim To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Methods Patients in clinical remission were treated with either mesalazine or the herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. Results A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either treatment. In contrast, CD4+ T cells, CD4+CD25medeffector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the herbal treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. Conclusions In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during treatment with myrrh, chamomile extract, and coffee charcoal than during treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. Trial Registration EU Clinical Trials Register 2007-007928-18/DE PMID:25144293

The effect of extracorporeal photopheresis alone or in combination therapy on circulating CD4+Foxp3+CD25- T-cells in patients with leukemic cutaneous T-cell lymphoma

PubMed Central

Shiue, Lisa H.; Couturier, Jacob; Lewis, Dorothy E.; Wei, Caimiao; Ni, Xiao; Duvic, Madeleine

2015-01-01

Purpose Extracorporeal photopheresis (ECP) alone or in combination therapy is effective for treatment of leukemic cutaneous T-cell lymphoma (L-CTCL), but its mechanism(s) of action remain unclear. This study was designed to investigate the effect of ECP on regulatory T-cell and CD8+ T-cells in L-CTCL patients. Experimental Design Peripheral blood from 18 L-CTCL patients at baseline, Day 2, 1-month, 3-month, and 6-month post-ECP therapy were analyzed by flow cytometry for CD4+CD25+/high, CD4+Foxp3+CD25+/-, CD3+CD8+, CD3+CD8+CD69+, and CD3+CD8+IFN-γ+ T-cells. Clinical responses were assessed and correlated with changes in these T-cell subsets. Results Twelve of 18 patients achieved clinical responses. The average baseline number of CD4+CD25+/high T-cells of PBMCs in L-CTCL patients was normal (2.2%), but increased at 6-month post-therapy (4.3%, p<0.01). The average baseline number of CD4+Foxp3+ T-cells out of CD4+ T-cells in 9 evaluable patients was high (66.8±13.7%), mostly CD25 negative. The levels of CD4+Foxp3+ T cells in responders were higher (n=6, 93.1±5.7%) than non-responders (n=3, 14.2±16.0%, p<0.01), and they declined in parallel with malignant T-cells. The numbers of CD3+CD8+CD69+ and CD3+CD8+ IFN-γ+ T-cells increased at 3-month post-therapy in 5 of 6 patients studied. Conclusions ECP alone or in combination therapy might be effective in L-CTCL patients whose malignant T-cells have a CD4+Foxp3+CD25- phenotype. PMID:25772268

No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRS CO13-HEPAVIH French cohort).

PubMed

Marcellin, Fabienne; Lions, Caroline; Rosenthal, Eric; Roux, Perrine; Sogni, Philippe; Wittkop, Linda; Protopopescu, Camelia; Spire, Bruno; Salmon-Ceron, Dominique; Dabis, François; Carrieri, Maria Patrizia

2017-03-01

Despite cannabis use being very common in patients co-infected with HIV and hepatitis C virus (HCV), its effect on these patients' immune systems remains undocumented. Documenting the potential effect of cannabis use on HIV immunological markers would help caregivers make more targeted health recommendations to co-infected patients. We performed a longitudinal analysis of the relationship between cannabis use and peripheral blood CD4 T-cell measures in co-infected patients receiving antiretroviral therapy. Cannabis use was assessed using annual self-administered questionnaires in 955 patients (2386 visits) enrolled in the ANRS CO13-HEPAVIH cohort. The effect of cannabis use on circulating CD4 T-cell count and percentage was estimated using multivariate linear regression models with generalised estimating equations. Sensitivity analyses were conducted after excluding visits where (i) tobacco use and (ii) smoking >=10 tobacco cigarettes/day were reported. At the first visit, 48% of patients reported cannabis use during the previous four weeks, and 58% of these patients also smoked ≥10 tobacco cigarettes/day. After multiple adjustment, cannabis use was not significantly associated with either circulating CD4 T-cell count [model coefficient (95% confidence interval): 0.27 (-0.07; 0.62), P = 0.12] or percentage [-0.04 (-0.45; 0.36), P = 0.83]. Sensitivity analyses confirmed these results. Findings show no evidence for a negative effect of cannabis use on circulating CD4 T-cell counts/percentages in HIV-HCV co-infected patients. In-depth immunological studies are needed to document whether cannabis has a harmful effect on CD4 levels in lungs and on cells' functional properties. [Marcellin F, Lions C, Rosenthal E, Roux P, Sogni P, Wittkop L, Protopopescu C, Spire B, Salmon-Ceron D, Dabis F, Carrieri MP, HEPAVIH ANRS CO13 Study Group. No significant effect of cannabis use on the count and percentage of circulating CD4 T-cells in HIV-HCV co-infected patients (ANRSCO13-HEPAVIH French cohort). Drug Alcohol Rev 2017;36:227-238]. © 2016 Australasian Professional Society on Alcohol and other Drugs.

Transitional probability-based model for HPV clearance in HIV-1-positive adolescent females.

PubMed

Kravchenko, Julia; Akushevich, Igor; Sudenga, Staci L; Wilson, Craig M; Levitan, Emily B; Shrestha, Sadeep

2012-01-01

HIV-1-positive patients clear the human papillomavirus (HPV) infection less frequently than HIV-1-negative. Datasets for estimating HPV clearance probability often have irregular measurements of HPV status and risk factors. A new transitional probability-based model for estimation of probability of HPV clearance was developed to fully incorporate information on HIV-1-related clinical data, such as CD4 counts, HIV-1 viral load (VL), highly active antiretroviral therapy (HAART), and risk factors (measured quarterly), and HPV infection status (measured at 6-month intervals). Data from 266 HIV-1-positive and 134 at-risk HIV-1-negative adolescent females from the Reaching for Excellence in Adolescent Care and Health (REACH) cohort were used in this study. First, the associations were evaluated using the Cox proportional hazard model, and the variables that demonstrated significant effects on HPV clearance were included in transitional probability models. The new model established the efficacy of CD4 cell counts as a main clearance predictor for all type-specific HPV phylogenetic groups. The 3-month probability of HPV clearance in HIV-1-infected patients significantly increased with increasing CD4 counts for HPV16/16-like (p<0.001), HPV18/18-like (p<0.001), HPV56/56-like (p = 0.05), and low-risk HPV (p<0.001) phylogenetic groups, with the lowest probability found for HPV16/16-like infections (21.60±1.81% at CD4 level 200 cells/mm(3), p<0.05; and 28.03±1.47% at CD4 level 500 cells/mm(3)). HIV-1 VL was a significant predictor for clearance of low-risk HPV infections (p<0.05). HAART (with protease inhibitor) was significant predictor of probability of HPV16 clearance (p<0.05). HPV16/16-like and HPV18/18-like groups showed heterogeneity (p<0.05) in terms of how CD4 counts, HIV VL, and HAART affected probability of clearance of each HPV infection. This new model predicts the 3-month probability of HPV infection clearance based on CD4 cell counts and other HIV-1-related clinical measurements.

Association between CD8 T-cell subsets and CD4/CD8 ratio with HS-CRP level in HIV-infected patients on antiretroviral therapy

NASA Astrophysics Data System (ADS)

Isabela, S.; Nugroho, A.; Harijanto, P. N.

2018-03-01

Due to improved access and adherence to antiretroviral therapy (ART), most HIV-infected persons worldwide are predicted to live longer. Nowadays the cause of death for most HIV-infected persons has changed to serious non-AIDS events (SNAEs) which is due to low-grade viremia. HIV patients with ART who had undergone CD4 cell count above 500/uL and there is an increase in hs-CRP despite an undetectable viral load. Some conditions CD8 cells count do not decrease with CD4 cells repairs. We researched in Prof Kandou General Hospital with a total sample of 35 HIV patients who had received ART with the level of CD4>350/uL. CD8 levels, CD4/CD8 ratio, and hs-CRP were assessed. This research is analytic descriptive with cross-sectional study design and analysis uses Spearman correlation. The mean CD8 during the study was 1291.8 (IQR 319-2610cells/uL), the mean ratio of CD4:CD8 was 0.57 (IQR 0.16-1.24) and median hs-CRP is 2.18 (IQR 0.3-6.6mg/dL). There was a significant positive correlation between CD8 and increased hs-CRP (r=0.369, p<0.05). There was a negative correlation between CD4/CD8 ratio and hs-CRP (r=-0.370, p<0.05).

Pretreatment CD4 Cell Slope and Progression to AIDS or Death in HIV-Infected Patients Initiating Antiretroviral Therapy—The CASCADE Collaboration: A Collaboration of 23 Cohort Studies

PubMed Central

Wolbers, Marcel; Babiker, Abdel; Sabin, Caroline; Young, Jim; Dorrucci, Maria; Chêne, Geneviève; Mussini, Cristina; Porter, Kholoud; Bucher, Heiner C.

2010-01-01

Background CD4 cell count is a strong predictor of the subsequent risk of AIDS or death in HIV-infected patients initiating combination antiretroviral therapy (cART). It is not known whether the rate of CD4 cell decline prior to therapy is related to prognosis and should, therefore, influence the decision on when to initiate cART. Methods and Findings We carried out survival analyses of patients from the 23 cohorts of the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) collaboration with a known date of HIV seroconversion and with at least two CD4 measurements prior to initiating cART. For each patient, a pre-cART CD4 slope was estimated using a linear mixed effects model. Our primary outcome was time from initiating cART to a first new AIDS event or death. We included 2,820 treatment-naïve patients initiating cART with a median (interquartile range) pre-cART CD4 cell decline of 61 (46–81) cells/µl per year; 255 patients subsequently experienced a new AIDS event or death and 125 patients died. In an analysis adjusted for established risk factors, the hazard ratio for AIDS or death was 1.01 (95% confidence interval 0.97–1.04) for each 10 cells/µl per year reduction in pre-cART CD4 cell decline. There was also no association between pre-cART CD4 cell slope and survival. Alternative estimates of CD4 cell slope gave similar results. In 1,731 AIDS-free patients with >350 CD4 cells/µl from the pre-cART era, the rate of CD4 cell decline was also not significantly associated with progression to AIDS or death (hazard ratio 0.99, 95% confidence interval 0.94–1.03, for each 10 cells/µl per year reduction in CD4 cell decline). Conclusions The CD4 cell slope does not improve the prediction of clinical outcome in patients with a CD4 cell count above 350 cells/µl. Knowledge of the current CD4 cell count is sufficient when deciding whether to initiate cART in asymptomatic patients. Please see later in the article for the Editors' Summary PMID:20186270

The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study.

PubMed

Cain, Lauren E; Phillips, Andrew; Lodi, Sara; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Tate, Janet; Logan, Roger; Robins, James M; Sterne, Jonathan A C; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C; Elzi, Luigia; Touloumi, Giota; Vourli, Georgia; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Rémonie; Meyer, Laurence; Pérez-Hoyos, Santiago; Muga, Roberto; Abgrall, Sophie; Costagliola, Dominique; Hernán, Miguel A

2012-08-24

To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

Age-Related Skeletal Muscle Decline Is Similar in HIV-Infected and Uninfected Individuals

PubMed Central

Yarasheski, Kevin E.; Scherzer, Rebecca; Kotler, Donald P.; Dobs, Adrian S.; Tien, Phyllis C.; Lewis, Cora E.; Kronmal, Richard A.; Heymsfield, Steven B.; Bacchetti, Peter

2011-01-01

Background. Skeletal muscle (SM) mass decreases with advanced age and with disease in HIV infection. It is unknown whether age-related muscle loss is accelerated in the current era of antiretroviral therapy and which factors might contribute to muscle loss among HIV-infected adults. We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls. Methods. Whole-body 1H-magnetic resonance imaging was used to quantify regional and total SM in 399 HIV-infected and 204 control men and women at baseline and 5 years later. Multivariable regression identified associated factors. Results. At baseline and Year 5, total SM was lower in HIV-infected than control men. HIV-infected women were similar to control women at both time points. After adjusting for demographics, lifestyle factors, and total adipose tissue, HIV infection was associated with lower Year 5 SM in men and higher SM in women compared with controls. Average overall 5-year change in total SM was small and age related, but rate of change was similar in HIV-infected and control men and women. CD4 count and efavirenz use in HIV-infected participants were associated with increasing SM, whereas age and stavudine use were associated with decreasing SM. Conclusions. Muscle mass was lower in HIV-infected men compared with controls, whereas HIV-infected women had slightly higher SM than control women after multivariable adjustment. We found evidence against substantially faster SM decline in HIV infected versus similar-aged controls. SM gain was associated with increasing CD4 count, whereas stavudine use may contribute to SM loss. PMID:21310810

High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

PubMed Central

Bedell, Richard A.; Anderson, Suzanne T. B.; van Lettow, Monique; Åkesson, Ann; Corbett, Elizabeth L.; Kumwenda, Moses; Chan, Adrienne K.; Heyderman, Robert S.; Zachariah, Rony; Harries, Anthony D.; Ramsay, Andrew R.

2012-01-01

Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations. PMID:22761767

Nutritional supplementation in HIV-infected individuals in South India: a prospective interventional study.

PubMed

Swaminathan, S; Padmapriyadarsini, C; Yoojin, L; Sukumar, B; Iliayas, S; Karthipriya, J; Sakthivel, R; Gomathy, P; Thomas, B E; Mathew, M; Wanke, C A; Narayanan, P R

2010-07-01

Malnutrition in human immunodeficiency virus (HIV)-infected individuals is associated with faster disease progression, higher mortality rates, and suboptimal response to antiretroviral therapy (ART). We conducted a prospective interventional study to evaluate the effects of an oral macronutrient supplement among HIV-infected adults in South India. Patients attending Tuberculosis Research Centre clinics from June 2005 through December 2007 had baseline nutritional assessment and laboratory investigations performed. Patients at 1 center received nutritional counseling and standard care, whereas patients at 2 centers additionally received a macronutrient providing 400 cal and 15 g of protein daily. Study outcomes were changes in anthropometry, body composition, blood chemistry, and immune status at 6 months. In total, 636 ART-naive patients were enrolled in the study; 361 completed 6 months of follow-up (282 received supplements and 79 received standard care). Mean age +/- standard deviation (SD) was 31 +/- 7 years, mean weight +/- SD was 50 +/- 10 kg, and 42% were male. Significant increases in body weight, body mass index, midarm circumference, fat-free mass, and body cell mass were observed in the supplement group but not in the control group at 6 months; gains were greater in patients with CD4 cell counts <200 cells/microL. No changes were observed in lipid levels, whereas the CD4 cell count decreased in the control group. However, after adjusting for baseline differences, these changes were not statistically significantly different between the groups. Macronutrient supplementation did not result in significantly increased weight gain compared with standard care (including nutritional counseling) among patients with moderately advanced HIV disease. The effect of supplementation on specific subsets of patients and on preserving immune function needs further research.

A randomized trial of ready-to-use supplementary food versus corn-soy blend plus as food rations for HIV-infected adults on antiretroviral therapy in rural Haiti.

PubMed

Ivers, Louise C; Teng, Jessica E; Jerome, J Gregory; Bonds, Matthew; Freedberg, Kenneth A; Franke, Molly F

2014-04-01

The epidemics of food insecurity, malnutrition, and human immunodeficiency virus (HIV) frequently overlap. HIV treatment programs increasingly provide nutrient-dense ready-to-use supplementary foods (RUSFs) to patients living with HIV and food insecurity, but in the absence of wasting, it is not known if RUSF confers benefit above less costly food commodities. We performed a randomized trial in rural Haiti comparing an RUSF with less costly corn-soy blend plus (CSB+) as a monthly supplement to patients with HIV infection who were on antiretroviral therapy (ART) <24 months prior to study start. We compared 6- and 12-month outcomes by ration type in terms of immunologic response, body mass index (BMI), adherence to ART, general health quality of life, household food insecurity, and household wealth. A cohort of 524 patients with HIV receiving ART was randomized and followed over time. Median CD4 cell count at baseline was 339 cells/µL (interquartile range [IQR], 197-475 cells/µL) for the CSB+ group, and 341 cells/µL (IQR, 213-464/µL) for the RUSF group. Measured outcomes improved from baseline over time, but there were no statistically significant differences in change for BMI, household wealth index, hunger, general health perception score, or adherence to ART by ration type at 6 or 12 months. The RUSF group had higher CD4 count at 12 months, but this was also not statistically significant. In 12 months of follow-up, there was no statistically significant difference in outcomes between those receiving RUSF-based compared with CSB+-based rations in a cohort of HIV-infected adults on ART in rural Haiti.

Pre-treatment drug resistance among patients initiating antiretroviral therapy (ART) in Zimbabwe: 2008-2010.

PubMed

Mungati, More; Mhangara, Mutsa; Gonese, Elizabeth; Mugurungi, Owen; Dzangare, Janet; Ngwende, Stella; Musasa, Patience; Wellington, Maureen; Shambira, Gerald; Apollo, Tsitsilina; Yang, Chunfu; DeVos, Joshua; Sabatier, Jennifer; Kilmarx, Peter; Chakanyuka-Musanhu, Christine; Tshimanga, Mufuta

2016-06-10

Zimbabwe set up 12 sentinel sites to monitor HIV drug resistance (HIVDR) following the international standards for prevention of HIVDR from 2008 to 2010. Participants were consecutively enrolled. Blood was collected and used for CD4 count, viral load (VL) and pre-treatment DR (PDR) tests besides routine baseline tests. We analyzed the characteristics of participants enrolled into the survey and estimated the point prevalence of PDR and its associated factors among ART initiators in a cross-sectional analysis using the baseline data collected from a prospective cohort in 12 purposefully selected sentinel sites. A total of 1728 participants (96 % response rate) were enrolled and 1610 had complete data. Of the 1610 there were more females (68.7 %) than males (31.3 %). The median CD4 count was 168 cells/mm(3) with males having lower values (P = 0.003). Ninety-six percent of participants had a VL ≥ 1000 copies/ml and the median VL was 128,000. Previous exposure to antiretroviral drugs (ARVs) was mainly through PMTCT (5 % of the participants). Overall, PDR mutations were detected in 6.3 % (95 % CI 5.2-7.7) of the 1480 successfully genotyped participants. However, the prevalence of PDR mutations was double for those with previous exposure (12.1 %) to ARVs compared with those without previous exposure (5.7 %, P = 0.002). The results show a moderate level of PDR prevalence among ART initiators. To maintain the efficacy of the current first-line regimens, there is need to strengthen all HIVDR prevention efforts and to conduct further studies to investigate optimal strategies that can prolong the efficacy of first-line ARV regimens in the country.

Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.

PubMed

Tenforde, Mark W; Yadav, Ashish; Dowdy, David W; Gupte, Nikhil; Shivakoti, Rupak; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Christian, Parul; Semba, Richard D; Campbell, Thomas B; Gupta, Amita

2017-07-01

Numerous micronutrients have immunomodulatory roles that may influence risk of tuberculosis (TB), but the association between baseline micronutrient deficiencies and incident TB after antiretroviral therapy (ART) initiation in HIV-infected individuals is not well characterized. We conducted a case-cohort study (n = 332) within a randomized trial comparing 3 ART regimens in 1571 HIV treatment-naive adults from 9 countries. A subcohort of 30 patients was randomly selected from each country (n = 270). Cases (n = 77; main cohort = 62, random subcohort = 15) included patients diagnosed with TB by 96 weeks post-ART initiation. We determined pretreatment concentrations of vitamin A, carotenoids, vitamin B6, vitamin B12, vitamin D, vitamin E, and selenium. We measured associations between pretreatment micronutrient deficiencies and incident TB using Breslow-weighted Cox regression models. Median pretreatment CD4 T-cell count was 170 cells/mm; 47.3% were women; and 53.6% Black. In multivariable models after adjusting for age, sex, country, treatment arm, previous TB, baseline CD4 count, HIV viral load, body mass index, and C-reactive protein, pretreatment deficiency in vitamin A (adjusted hazard ratio, aHR 5.33, 95% confidence interval, CI: 1.54 to 18.43) and vitamin D (aHR 3.66, 95% CI: 1.16 to 11.51) were associated with TB post-ART. In a diverse cohort of HIV-infected adults from predominantly low- and middle-income countries, deficiencies in vitamin A and vitamin D at ART initiation were independently associated with increased risk of incident TB in the ensuing 96 weeks. Vitamin A and D may be important modifiable risk factors for TB in high-risk HIV-infected patients starting ART in resource-limited highly-TB-endemic settings.

Pregnancy incidence and outcomes in women with perinatal HIV infection.

PubMed

Byrne, Laura; Sconza, Rebecca; Foster, Caroline; Tookey, Pat A; Cortina-Borja, Mario; Thorne, Claire

2017-07-31

To estimate the incidence of first pregnancy in women living with perinatally acquired HIV (PHIV) in the United Kingdom and to compare pregnancy management and outcomes with age-matched women with behaviourally acquired HIV (BHIV). The National Study of HIV in Pregnancy and Childhood is a comprehensive, population-based surveillance study that collects demographic and clinical data on all pregnant women living with HIV, their children, and all HIV-infected children in the United Kingdom and Ireland. The incident rate ratio of first pregnancy was calculated for all women of reproductive age who had been reported to the National Study of HIV in Pregnancy and Childhood as vertically infected children. These women and their pregnancies were compared to age-matched pregnant women with BHIV. Of the 630 women with PHIV reported in the United Kingdom as children, 7% (45) went on to have at least one pregnancy, with 70 pregnancies reported. The incident rate ratio of first pregnancy was 13/1000 woman-years. The BHIV comparison group comprised 118 women (184 pregnancies). Women with PHIV were more likely to be on combined antiretroviral therapy at conception and have a lower baseline CD4 cell count (P < 0.01 for both). In adjusted analysis, PHIV and a low baseline CD4 cell count were risk factors for detectable viral load near delivery; older age at conception and being on combined antiretroviral therapy at conception reduced this risk. Women with PHIV in the United Kingdom have a low pregnancy incidence, but those who become pregnant are at risk of detectable viral load near delivery, reflecting their often complex clinical history, adherence, and drug resistance issues.

A Five-Year Longitudinal Analysis of Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus Reveals a Slow but Progressive Decline in CD4+ T-Cell Count Whose Magnitude Is Not Predicted by Viral Load or Immune Activation▿

PubMed Central

Taaffe, Jessica; Chahroudi, Ann; Engram, Jessica; Sumpter, Beth; Meeker, Tracy; Ratcliffe, Sarah; Paiardini, Mirko; Else, James; Silvestri, Guido

2010-01-01

Natural simian immunodeficiency virus (SIV) infection in sooty mangabeys (SMs) typically does not result in AIDS, despite high-level viremia and significant depletion of mucosal CD4+ T cells. Here, we report the results of the first longitudinal study of a large cohort of SMs naturally infected with SIV (n = 78) housed at the Yerkes National Primate Research Center from which samples were obtained three times over a 5-year period. In this study, we observed (i) no signs of simian AIDS, (ii) stable SIV loads, (iii) a slow but progressive decline in CD4+ T-cell counts (from a mean of 1,067.0 cells/mm3 at time point 1 to 764.8 cells/mm3 at time point 3) and increases in the numbers of animals with CD4+ T-cell levels below 500 and 200 cells/mm3 (from 8 to 28 of 78 and from 1 to 4 of 78, respectively), (iv) progressive declines in percentages of naïve CD4+ and CD8+ T cells (from 37.7 to 24.8% and from 21.0 to 13.0%, respectively), and (v) stably low levels of activated/proliferating T cells as well as CD4+ CCR5+ T cells. Since the level of total CD4+ T cells and the fraction of naïve T cells in SIV-uninfected SMs also declined, it is possible that some of these observations are related to aging, as the SIV-infected animals were significantly older than the uninfected animals. In contrast to the decline in CD4+ T cell counts in individuals infected with human immunodeficiency virus (HIV), the decline in CD4+ T cell counts in SMs naturally infected with SIV over a 5-year period was not predicted by either plasma viremia or levels of T-cell activation. Taken together, these results confirm that natural SIV infection is nonprogressive from a clinical, virological, and immunological point of view and that stable levels of viremia associated with persistently low-level immune activation represent key differences from the natural course of HIV infection in humans. PMID:20335252

A five-year longitudinal analysis of sooty mangabeys naturally infected with simian immunodeficiency virus reveals a slow but progressive decline in CD4+ T-cell count whose magnitude is not predicted by viral load or immune activation.

PubMed

Taaffe, Jessica; Chahroudi, Ann; Engram, Jessica; Sumpter, Beth; Meeker, Tracy; Ratcliffe, Sarah; Paiardini, Mirko; Else, James; Silvestri, Guido

2010-06-01

Natural simian immunodeficiency virus (SIV) infection in sooty mangabeys (SMs) typically does not result in AIDS, despite high-level viremia and significant depletion of mucosal CD4(+) T cells. Here, we report the results of the first longitudinal study of a large cohort of SMs naturally infected with SIV (n = 78) housed at the Yerkes National Primate Research Center from which samples were obtained three times over a 5-year period. In this study, we observed (i) no signs of simian AIDS, (ii) stable SIV loads, (iii) a slow but progressive decline in CD4(+) T-cell counts (from a mean of 1,067.0 cells/mm(3) at time point 1 to 764.8 cells/mm(3) at time point 3) and increases in the numbers of animals with CD4(+) T-cell levels below 500 and 200 cells/mm(3) (from 8 to 28 of 78 and from 1 to 4 of 78, respectively), (iv) progressive declines in percentages of naïve CD4(+) and CD8(+) T cells (from 37.7 to 24.8% and from 21.0 to 13.0%, respectively), and (v) stably low levels of activated/proliferating T cells as well as CD4(+) CCR5(+) T cells. Since the level of total CD4(+) T cells and the fraction of naïve T cells in SIV-uninfected SMs also declined, it is possible that some of these observations are related to aging, as the SIV-infected animals were significantly older than the uninfected animals. In contrast to the decline in CD4(+) T cell counts in individuals infected with human immunodeficiency virus (HIV), the decline in CD4(+) T cell counts in SMs naturally infected with SIV over a 5-year period was not predicted by either plasma viremia or levels of T-cell activation. Taken together, these results confirm that natural SIV infection is nonprogressive from a clinical, virological, and immunological point of view and that stable levels of viremia associated with persistently low-level immune activation represent key differences from the natural course of HIV infection in humans.

Transient expansion of activated CD8+ T cells characterizes tuberculosis-associated immune reconstitution inflammatory syndrome in patients with HIV: a case control study

PubMed Central

2013-01-01

Background CD4+ T cell activation indicators have been reported to be a common phenomenon underlying diverse manifestations of immune reconstitution inflammatory syndrome (IRIS). However, we have found that a high frequency of circulating CD8+ T cells is a specific risk factor for mycobacterial IRIS. Therefore, we investigated whether CD8+ T cells from patients who develop TB IRIS were specifically activated. Methods We obtained PBMCs from HIV+ patients prior to and 4, 8, 12, 24, 52 and 104 weeks after initiating antiretroviral therapy. CD38 and HLADR expression on naive, central memory and effector memory CD8+ and CD4+ T cells were determined by flow cytometry. Absolute counts and frequencies of CD8+ T cell subsets were compared between patients who developed TB IRIS, who developed other IRIS forms and who remained IRIS-free. Results TB IRIS patients showed significantly higher counts of naive CD8+ T cells than the other groups at most time points, with a contraction of the effector memory subpopulation occurring later in the follow-up period. Activated (CD38+ HLADR+) CD8+ T cells from all groups decreased with treatment but transiently peaked in TB IRIS patients. This increase was due to an increase in activated naive CD8+ T cell counts during IRIS. Additionally, the CD8+ T cell subpopulations of TB IRIS patients expressed HLADR without CD38 more frequently and expressed CD38 without HLADR less frequently than cells from other groups. Conclusions CD8+ T cell activation is specifically relevant to TB IRIS. Different IRIS forms may involve different alterations in T cell subsets, suggesting different underlying inflammatory processes. PMID:23688318

ELISPOTs Produced by CD8 and CD4 Cells Follow Log Normal Size Distribution Permitting Objective Counting

PubMed Central

Karulin, Alexey Y.; Karacsony, Kinga; Zhang, Wenji; Targoni, Oleg S.; Moldovan, Ioana; Dittrich, Marcus; Sundararaman, Srividya; Lehmann, Paul V.

2015-01-01

Each positive well in ELISPOT assays contains spots of variable sizes that can range from tens of micrometers up to a millimeter in diameter. Therefore, when it comes to counting these spots the decision on setting the lower and the upper spot size thresholds to discriminate between non-specific background noise, spots produced by individual T cells, and spots formed by T cell clusters is critical. If the spot sizes follow a known statistical distribution, precise predictions on minimal and maximal spot sizes, belonging to a given T cell population, can be made. We studied the size distributional properties of IFN-γ, IL-2, IL-4, IL-5 and IL-17 spots elicited in ELISPOT assays with PBMC from 172 healthy donors, upon stimulation with 32 individual viral peptides representing defined HLA Class I-restricted epitopes for CD8 cells, and with protein antigens of CMV and EBV activating CD4 cells. A total of 334 CD8 and 80 CD4 positive T cell responses were analyzed. In 99.7% of the test cases, spot size distributions followed Log Normal function. These data formally demonstrate that it is possible to establish objective, statistically validated parameters for counting T cell ELISPOTs. PMID:25612115

Live attenuated herpes zoster vaccine for HIV-infected adults.

PubMed

Shafran, S D

2016-04-01

Multiple guidelines exist for the use of live viral vaccines for measles-mumps-rubella (MMR), varicella and yellow fever in people with HIV infections, but these guidelines do not make recommendations regarding live attenuated herpes zoster vaccine (LAHZV), which is approved for people over 50 years in the general population. LAHZV is made with the same virus used in varicella vaccine. The incidence of herpes zoster remains increased in people with HIV infection, even when on suppressive antiretroviral therapy, and a growing proportion of HIV-infected patients are over 50 years of age. The purpose of this article is to review the use of varicella vaccine and LAHZV in people with HIV infection and to make recommendations about the use of LAHZV in adults with HIV infection. A PubMed search was undertaken using the terms 'herpes zoster AND HIV' and 'varicella AND HIV'. Reference lists were also reviewed for pertinent citations. Varicella vaccine is recommended in varicella-susceptible adults, as long as they have a CD4 count > 200 cells/μL, the same CD4 threshold used for MMR and yellow fever vaccines. No transmission of vaccine strain Varicella zoster virus has been documented in people with HIV infections with a CD4 count above this threshold. LAHZV was administered to 295 HIV-infected adults with a CD4 count > 200 cells/μL, and was safe and immunogenic with no cases of vaccine strain infection. It is recommended that LAHZV be administered to HIV-infected adults with a CD4 count above 200 cells/μL, the same CD4 threshold used for other live attenuated viral vaccines. © 2015 British HIV Association.

Intensification of Antiretroviral Therapy with a CCR5 Antagonist in Patients with Chronic HIV-1 Infection: Effect on T Cells Latently Infected

PubMed Central

Vallejo, Alejandro; Hernández-Novoa, Beatriz; Abad, María; Madrid, Nadia; Dahl, Viktor; Rubio, Rafael; Moreno, Ana M.; Dronda, Fernando; Casado, José Luis; Navas, Enrique; Pérez-Elías, María Jesús; Zamora, Javier; Palmer, Sarah; Muñoz, Eduardo; Muñoz-Fernández, María Ángeles; Moreno, Santiago

2011-01-01

Objective The primary objective was to assess the effect of MVC intensification on latently infected CD4+ T cells in chronically HIV-1-infected patients receiving antiretroviral therapy. Methods We performed an open-label pilot phase II clinical trial involving chronically HIV-1-infected patients receiving stable antiretroviral therapy whose regimen was intensified with 48 weeks of maraviroc therapy. We analyzed the latent reservoir, the residual viremia and episomal 2LTR DNA to examine the relationship between these measures and the HIV-1 latent reservoir, immune activation, lymphocyte subsets (including effector and central memory T cells), and markers associated with bacterial translocation. Results Overall a non significant reduction in the size of the latent reservoir was found (p = 0.068). A mean reduction of 1.82 IUPM was observed in 4 patients with detectable latent reservoir at baseline after 48 weeks of intensification. No effect on plasma residual viremia was observed. Unexpectedly, all the patients had detectable 2LTR DNA circles at week 24, while none of them showed those circles at the end of the study. No changes were detected in CD4+ or CD8+ counts, although a significant decrease was found in the proportion of HLA-DR+/CD38+ CD4+ and CD8+ T-cells. LPS and sCD14 levels increased. Conclusions Intensification with MVC was associated with a trend to a decrease in the size of the latent HIV-1 reservoir in memory T cells. No impact on residual viremia was detected. Additional studies with larger samples are needed to confirm the results. Trial Registration ClinicalTrials.gov NCT00795444 PMID:22174752

Clinical manifestations of treatment-naive patients with acquired immunodeficiency syndrome and responses to highly active antiretroviral therapy in the Taipei Veterans General Hospital: a 5-year prospective study.

PubMed

Hsu, Shih-Fen; Yang, Su-Pen; Chan, Yu-Jiun; Wang, Yung-Wei

2011-06-01

Taipei Veterans General Hospital, one of the medical centers in Taiwan, has provided highly active antiretroviral therapy (HAART) to human immunodeficiency virus/AIDS patients for more than 10 years. Five years ago, we began a prospective follow-up of our patients' clinical manifestations and responses to HAART by collecting their clinical data. In this study, we analyzed the morbidity, mortality, and responses to HAART of treatment-naive AIDS patients. The purpose was to provide local data that may be valuable in Taiwan. Study cases were enrolled from January 1, 2004, to February 28, 2009, with inclusion criteria of newly diagnosed AIDS during hospitalization and being naive to HAART. Antiretroviral therapy was initiated. To evaluate the clinical responses to HAART, we excluded patients who were pregnant, died within 1 month after confirmation of an AIDS diagnosis, failed to initiate HAART, or were lost to follow-up for more than 6 months. Plasma viral loads and CD4(+) counts were quantified by reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. Statistical analysis was performed using SPSS statistical software. A total of 49 patients were enrolled and 45 patients fulfilled the inclusion criteria for evaluating the efficacy of HAART. At 3 months, 12 months, and 30 months after the initiation of HAART, 64.4% (29 of 45), 88.2% (30 of 34), and 93.8% (15 of 16) had undetectable plasma viral loads, respectively, and 37.8% (17 of 45), 73.5% (25 of 34), and 81.2% (13 of 16) had CD4(+) counts of more than 200 cells/μL, respectively. Median CD4(+) counts increased from baseline at Month 3 by 171 cells/μL and at Month 30 by 375 cells/μL. The overall mortality was 22.4% (11 of 49). The virologic and immunologic responses after initiating HAART in this study demonstrated our achievements in providing care and treatment for AIDS patients during this 5-year period, which provides a strong evidence of the efficacy of HAART. Copyright © 2011. Published by Elsevier B.V.

Cost-effectiveness of community-based strategies to strengthen the continuum of HIV care in rural South Africa: a health economic modelling analysis.

PubMed

Smith, Jennifer A; Sharma, Monisha; Levin, Carol; Baeten, Jared M; van Rooyen, Heidi; Celum, Connie; Hallett, Timothy B; Barnabas, Ruanne V

2015-04-01

Home HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis we aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa. We parameterised an individual-based model with data from home HTC and linkage field studies that achieved high coverage (91%) and linkage to antiretroviral therapy (80%) in rural KwaZulu-Natal, South Africa. Costs were derived from a linked microcosting study. The model simulated 10,000 individuals over 10 years and incremental cost-effectiveness ratios were calculated for the intervention relative to the existing status quo of facility-based testing, with costs discounted at 3% annually. The model predicted implementation of home HTC in addition to current practice to decrease HIV-associated morbidity by 10–22% and HIV infections by 9–48% with increasing CD4 cell count thresholds for antiretroviral therapy initiation. Incremental programme costs were US$2·7 million to $4·4 million higher in the intervention scenarios than at baseline, and costs increased with higher CD4 cell count thresholds for antiretroviral therapy initiation; antiretroviral therapy accounted for 48–87% of total costs. Incremental cost-effectiveness ratios per disability-adjusted life-year averted were $1340 at an antiretroviral therapy threshold of CD4 count lower than 200 cells per μL, $1090 at lower than 350 cells per μL, $1150 at lower than 500 cells per μL, and $1360 at universal access to antiretroviral therapy. Community-based HTC with enhanced linkage to care can result in increased HIV testing coverage and treatment uptake, decreasing the population burden of HIV-associated morbidity and mortality. The incremental cost-effectiveness ratios are less than 20% of South Africa's gross domestic product per person, and are therefore classed as very cost effective. Home HTC can be a viable means to achieve UNAIDS' ambitious new targets for HIV treatment coverage. National Institutes of Health, Bill & Melinda Gates Foundation, Wellcome Trust.

Alcohol use disorders among people living with HIV/AIDS in Southern Brazil: prevalence, risk factors and biological markers outcomes.

PubMed

da Silva, Cláudio Moss; Mendoza-Sassi, Raúl Andrés; da Mota, Luisa Dias; Nader, Maíba Mikhael; de Martinez, Ana Maria Barral

2017-04-11

Alcohol abuse is an important public health problem, frequently unrecognized among people living with HIV/AIDS (PLWHA), and requires investigation and intervention. It is usually associated with lower adherence to highly active antiretroviral therapy (HAART). It can also produce adverse clinical outcomes, such as changes in certain HIV markers, particularly CD4 cell counts and HIV viral loads (VLs). Thus, this study aimed to evaluate the prevalence of alcohol abuse among PLWHA, its associated risk factors and effects on CD4 cell counts and HIV VLs in southern Brazil. Between December 2012 and July 2013, 343 patients were interviewed at a reference hospital in southern Brazil. The instrument used was the Alcohol Use Disorder Identification Test (AUDIT), and a cutoff of eight points or more was applied. Socioeconomic, demographic, clinical and laboratory data were also collected. The statistical analysis included a Poisson regression to evaluate the factors associated with alcohol use disorder, and a linear regression was performed to assess the relationship between AUDIT scores and CD4 cell counts and HIV VLs. Alcohol abuse was present in 28.6% of the respondents, and possible dependence was present in 5%. The risk factors identified included being male, mixed or black skin color, low education and the use of intravenous or inhaled drugs. A higher AUDIT score was associated with a lower CD4 cell count but was not associated with higher HIV VL values. Our results show the importance of screening for alcohol abuse in this group. The prevalence of alcohol abuse was high, and it was associated with socioeconomic factors and the use of illicit drugs. Moreover, AUDIT score negatively affected CD4 cell counts as well.

Amino Acid Concentrations in HIV-Infected Youth Compared to Healthy Controls and Associations with CD4 Counts and Inflammation.

PubMed

Ziegler, Thomas R; Judd, Suzanne E; Ruff, Joshua H; McComsey, Grace A; Eckard, Allison Ross

2017-07-01

Amino acids play critical roles in metabolism, cell function, body composition and immunity, but little data on plasma amino acid concentrations in HIV are available. We evaluated plasma amino acid concentrations and associations with CD4 counts and inflammatory biomarkers in HIV-infected youth. HIV-infected subjects with a high (≥500 cells/mm 3 ) and low (<500 cells/mm 3 ) current CD4 + T cell counts were compared to one another and to a matched healthy control group. Plasma concentrations of 19 amino acids were determined with an amino acid analyzer. Plasma levels of interleukin-6, tumor necrosis factor receptor-I, and soluble vascular cellular adhesion molecule-I were also measured. Seventy-nine HIV-infected subjects (40 and 39 with high and low CD4 + T cell counts, respectively) and 40 controls were included. There were no differences in amino acid concentrations between HIV-infected subjects with high or low CD4 + T cell counts. When combined, the HIV-infected group exhibited significantly lower median plasma concentrations compared to controls for total, essential, branched-chain and sulfur amino acids, as well as for 12 individual amino acids. Glutamate was the only amino acid that was higher in the HIV-infected group. There were no significant correlations between amino acid endpoints and inflammatory biomarkers for either HIV-infected group or controls. Plasma amino acid concentrations were lower in HIV-infected youth compared to healthy controls, regardless of immune status, while glutamate concentrations were elevated. These findings can inform future interventional studies designed to improve metabolic and clinical parameters influenced by amino acid nutriture.

Program Implementation of Option B+ at a President's Emergency Plan for AIDS Relief-Supported HIV Clinic Improves Clinical Indicators But Not Retention in Care in Mbarara, Uganda.

PubMed

Miller, Kathleen; Muyindike, Winnie; Matthews, Lynn T; Kanyesigye, Michael; Siedner, Mark J

2017-08-01

2013 WHO guidelines for prevention of mother to child transmission recommend combination antiretroviral therapy (ART) for all pregnant women, regardless of CD4 count (Option B/B+). We conducted a retrospective analysis of data from a government-operated HIV clinic in Mbarara, Uganda before and after implementation of Option B+ to assess the impact on retention in care. We limited our analysis to women not on ART at the time of their first reported pregnancy with CD4 count >350. We fit regression models to estimate relationships between calendar period (Option A vs. Option B+) and the primary outcome of interest, retention in care. One thousand and sixty-two women were included in the analysis. Women were more likely to start ART within 6 months of pregnancy in the Option B+ period (68% vs. 7%, p < 0.0001) and had significantly greater increases in CD4 count 1 year after pregnancy (+172 vs. -5 cells, p < 0.001). However, there was no difference in the proportion of women retained in care 1 year after pregnancy (73% vs. 70%, p = 0.34). In models adjusted for age, distance to clinic, marital status, and CD4 count, Option B+ was associated with a nonsignificant 30% increased odds of retention in care at 1 year [adjusted odds ratio (AOR) = 1.30, 95% CI 0.98-1.73, p = 0.06]. After transition to an Option B+ program, pregnant women with CD4 count >350 were more likely to initiate combination therapy; however, interventions to mitigate losses from HIV care during pregnancy are needed to improve the health of women, children, and families.

Low CD4+ T cell count as a major atherosclerosis risk factor in HIV-infected women and men

PubMed Central

Kaplan, Robert C; Kingsley, Lawrence A; Gange, Stephen J; Benning, Lorie; Jacobson, Lisa P; Lazar, Jason; Anastos, Kathryn; Tien, Phyllis C; Sharrett, A Richey; Hodis, Howard N

2009-01-01

Objective To assess the association of HIV infection, HIV disease parameters (including CD4+ T-cell counts, HIV viral load, and AIDS) and antiretroviral medication use with subclinical carotid artery atherosclerosis. Design Cross-sectional study nested within a prospective cohort study Methods Among participants in the Women's Interagency HIV Study (1,331 HIV-infected women, 534 HIV-uninfected women) and Multicenter AIDS Cohort Study (600 HIV-infected men, 325 HIV-uninfected men), we measured subclinical carotid artery lesions and common carotid artery intima-media thickness (CIMT) using B-mode ultrasound. We estimated adjusted mean CIMT differences and prevalence ratios (PRs) for carotid lesions associated with HIV-related disease and treatments, with multivariate adjustment to control for possible confounding variables. Results Among HIV-infected individuals, a low CD4+ T cell count was independently associated with an increased prevalence of carotid lesions. Compared to the reference group of HIV-uninfected individuals, the adjusted PR for lesions among HIV-infected individuals with CD4+ T-cell count <200 cells/mm3 was 2.00 (95% confidence interval 1.22, 3.28) in women and 1.74 (95% confidence interval 1.04, 2.93) in men. No consistent association of antiretroviral medications with carotid atherosclerosis was observed, except for a borderline significant association between protease inhibitor use and carotid lesions in men (with no association among women). History of clinical AIDS and HIV viral load were not significantly associated with carotid atherosclerosis. Conclusions Beyond traditional cardiovascular disease risk factors, low CD4+ T-cell count is the most robust risk factor for increased subclinical carotid atherosclerosis in HIV-infected women and men. PMID:18670221

The effect of a "universal antiretroviral therapy" recommendation on HIV RNA levels among HIV-infected patients entering care with a CD4 count greater than 500/μL in a public health setting.

PubMed

Geng, Elvin H; Hare, C Bradley; Kahn, James O; Jain, Vivek; Van Nunnery, Tracy; Christopoulos, Katerina A; Deeks, Steven G; Gandhi, Monica; Havlir, Diane V

2012-12-01

On 1 January 2010, a large, publicly funded clinic in San Francisco announced a "universal ART" approach to initiate antiretroviral therapy (ART) in all human immunodeficiency virus (HIV)-infected persons. The effect of changing guidance on real-world patient outcomes has not been evaluated. We evaluated untreated adult patients (defined as going >90 days without ART use) visiting clinic from 2001 to 2011. The cumulative incidence of HIV RNA suppression (viral load, <500 copies/mL), stratified by CD4 cell count at entry and calendar dates representing guideline issuance, were estimated using a competing risk framework. A multivariate Poisson-based model identified factors associated with HIV RNA suppression 6 months after clinic entry. Of 2245 adults, 87% were male, and the median age was 39 years (interquartile range, 33-45 years). In 534 patients entering clinic with a CD4 cell count of >500 cells/µL, the 1-year incidence of HIV RNA suppression was 10.1% (95% confidence interval [CI], 6.6%-14.6%) before 4 April 2005; 9.1% (95% CI, 3.6%-17.4%) from 4 April 2005 to 1 December 2007; 14.1% (95% CI, 7.5%-22.8%) from 1 December 2007 to the universal ART recommendation and 52.8% (95% CI, 38.2%-65.4%) after. After adjustment, the SFGH policy was associated with a 6-fold increase in the probability of HIV RNA suppression 6 months after clinic entry. Recommendations to initiate ART in all HIV-infected patients increased the rate of HIV RNA suppression for patients enrolling in care with a CD4 cell count of >500 cells/µL and may foreshadow national trends given the March 2012 revision of national treatment guidelines to favor ART initiation for persons with CD4 cell counts of >500 cells/µL.

Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy.

PubMed

Kesselring, S; Cescon, A; Colley, G; Osborne, C; Zhang, W; Raboud, J M; Hosein, S R; Burchell, A N; Cooper, C; Klein, M B; Loutfy, M; Machouf, N; Montaner, Jsg; Rachlis, A; Tsoukas, C; Hogg, R S; Lima, V D

2017-03-01

To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm 3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible. © 2016 British HIV Association.

Nelfinavir and non-nucleoside reverse transcriptase inhibitor-based salvage regimens in heavily HIV pretreated patients

PubMed Central

Baril, Jean-Guy; Lefebvre, Eric A; Lalonde, Richard G; Shafran, Stephen D; Conway, Brian

2003-01-01

OBJECTIVE: To assess the efficacy of nelfinavir mesylate (NFV) in combination with delavirdine mesylate (DLV) or efavirenz (EFV) and other antiretroviral agents following virological failure on other protease inhibitor (PI)-based regimens. DESIGN: Multicentre, retrospective chart review. METHODS: One hundred-one patients who were naive to both NFV and non-nucleoside reverse transcriptase inhibitors (NNRTIs) and who initiated NFV plus DLV or EFV-based salvage regimens were reviewed. Response to treatment was defined as a reduction in HIV ribonucleic acid (RNA) levels to unquantifiable levels (less than 50 copies/mL, less than 400 copies/mL, less than 500 copies/mL) on at least one occasion after the initiation of salvage therapy. Baseline correlates of response, including prior duration of HIV infection, prior number of regimens, viral load and CD4 cell counts were also evaluated. RESULTS: Patients had a mean duration of HIV infection of 10 years, a mean duration of prior therapy of four years, a median of four prior nucleoside reverse transcriptase inhibitors and a median of two prior PIs. At the time of review the mean duration of salvage therapy was 63.4 weeks. Virological suppression was achieved in 59 (58.4%) patients within a mean of eight weeks and maintained for a mean of 44.9 weeks (the mean follow-up was 78 weeks). Of the non-responders, 16 (38%) achieved a less than 1 log10 decrease in HIV RNA levels. Although there was no association between baseline correlates, response rate (75.7%) was significantly higher in patients with HIV RNA levels of 50,000 copies/mL or lower and CD4 counts greater than 200 cells/mm3. CONCLUSION: NFV/NNRTI-based highly active antiretroviral therapy regimens are an effective therapy in many patients who have experienced virological breakthroughs on at least one prior PI-based regimen. PMID:18159457

Cervical cancer screening intervals and management for women living with HIV: a risk benchmarking approach.

PubMed

Robbins, Hilary A; Strickler, Howard D; Massad, L Stewart; Pierce, Christopher B; Darragh, Teresa M; Minkoff, Howard; Keller, Marla J; Fischl, Margaret; Palefsky, Joel; Flowers, Lisa; Rahangdale, Lisa; Milam, Joel; Shrestha, Sadeep; Colie, Christine; DʼSouza, Gypsyamber

2017-04-24

We suggested cervical cancer screening strategies for women living with HIV (WLHIV) by comparing their precancer risks to general population women, and then compared our suggestions with current Centers for Disease Control and Prevention (CDC) guidelines. We compared risks of biopsy-confirmed cervical high-grade squamous intraepithelial neoplasia or worse (bHSIL+), calculated among WLHIV in the Women's Interagency HIV Study, to 'risk benchmarks' for specific management strategies in the general population. We applied parametric survival models among 2423 WLHIV with negative or atypical squamous cell of undetermined significance (ASC-US) cytology during 2000-2015. Separately, we synthesized published general population bHSIL+ risks to generate 3-year risk benchmarks for a 3-year return (after negative cytology, i.e. 'rescreening threshold'), a 6-12-month return (after ASC-US), and immediate colposcopy [after low-grade squamous intraepithelial lesion (LSIL)]. Average 3-year bHSIL+ risks among general population women ('risk benchmarks') were 0.69% for a 3-year return (after negative cytology), 8.8% for a 6-12-month return (after ASC-US), and 14.4% for colposcopy (after LSIL). Most CDC guidelines for WLHIV were supported by comparing risks in WLHIV to these benchmarks, including a 3-year return with CD4 greater than 500 cells/μl and after either three negative cytology tests or a negative cytology/oncogenic human papillomavirus cotest (all 3-year risks≤1.3%); a 1-year return after negative cytology with either positive oncogenic human papillomavirus cotest (1-year risk = 1.0%) or CD4 cell count less than 500 cells/μl (1-year risk = 1.1%); and a 6-12-month return after ASC-US (3-year risk = 8.2% if CD4 cell count at least 500 cells/μl; 10.4% if CD4 cell count = 350-499 cells/μl). Other suggestions differed modestly from current guidelines, including colposcopy (vs. 6-12 month return) for WLHIV with ASC-US and CD4 cell count less than 350 cells/μl (3-year risk = 16.4%) and a lengthened 2-year (vs. 1-year) interval after negative cytology with CD4 cell count at least 500 cells/μl (2-year risk = 0.98%). Current cervical cancer screening guidelines for WLHIV are largely appropriate. CD4 cell count may inform risk-tailored strategies.

The changes in the T-lymphocyte subsets in a population of Turkish children with puberty gingivitis.

PubMed

Demir, Turgut; Orbak, Recep; Tezel, Adnan; Canakç, Varol; Kaya, Hasan

2009-05-01

The aim of the study was to investigate the number of CD4 and CD8 T lymphocytes, analyse subjects with gingivitis and those without, and determine the role of T lymphocytes in the pathobiology of puberty gingivitis. Fifty individuals with and without puberty gingivitis were recruited for this study. The CD4(+) and CD8(+) T-lymphocyte counts were determined using flow cytometry on the biopsy samples, and the CD4(+)/CD8(+) ratio was calculated. At the same time, periodontal index scores were recorded to assess the periodontal status. Acquired data were analysed statistically using a paired t-test to compare laboratory values obtained before and after the treatment in individuals with puberty gingivitis and disease-free individuals. In addition, Pearson's correlation analysis was performed to investigate the relation between laboratory values and clinical measurements. The CD4(+)/CD8 ratio in gingival tissues obtained from test group was significantly higher (P < 0.05) than that found in the gingival tissue obtained from control group. We found that the CD4(+) and CD8(+) lymphocyte counts continued to increase significantly (P < 0.001) and the CD4(+)/CD8(+) ratio continued to drop significantly (P < 0.05) after treatment in test group. T lymphocytes could play a significant role in the pathobiology of puberty gingivitis.

Switch from unboosted protease inhibitor to a single-tablet regimen containing rilpivirine improves cholesterol and triglycerides.

PubMed

Di Biagio, Antonio; Riccardi, Niccolò; Taramasso, Lucia; Capetti, Amedeo; Cenderello, Giovanni; Signori, Alessio; Vitiello, Paola; Guerra, Michele; de Socio, Giuseppe Vittorio; Cassola, Giovanni; Quirino, Tiziano; Viscoli, Claudio

2016-11-01

This study aimed to evaluate the efficacy, tolerability and potential savings of combined antiretroviral therapy (cART) simplification from an unboosted protease inhibitor (PI) regimen with atazanavir or fosamprenavir to a single-tablet regimen (STR) based on rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) among HIV-1-infected patients with HIV-1 RNA <50 copies/mL. This was a retrospective, multicentre, open-label, 12-week trial. Plasma HIV-1-RNA levels, CD4+ cell counts, cholesterol, triglycerides, bilirubin, glycaemia, creatinine and physical examination were performed at baseline and at scheduled follow-up. All patient costs were calculated and were estimated for 52 weeks of therapy. Fifty-one patients were enrolled [28 male (54.9%)]. At baseline, 30 patients (58.8%) were treated with FTC/TDF, 20 (39.2%) with abacavir/lamivudine and 1 (2.0%) with lamivudine/zidovudine. Thirty-three patients (64.7%) received atazanavir. All patients maintained HIV-RNA <50 copies/mL; the median CD4+ cell count remained stable. Mean triglycerides decreased from 124 mg/dL (range, 39-625) at enrolment to 108.7 mg/dL (range, 39-561) at study end (P = 0.25). At baseline, mean cholesterol was 172.8 ± 38.1 mg/dL and decreased to 161.9 ± 38.6 mg/dL (P = 0.038); likewise, median total bilirubin decreased from 1.07 mg/dL (range, 0.2-4.7) to 0.6 mg/dL (range, 0.13-3.1) (P <0.001). cART-related annual cost reduction with a STR was €3155.47 per patient (-24%). Non-cART patient management expenses were €402.68 vs. €299.10 for atazanavir or fosamprenavir and STR regimens, respectively. Switching to RPV/FTC/TDF from an unboosted PI in virologically suppressed HIV-infected patients is safe and is associated with a reduction in triglycerides, cholesterol and cART-related costs. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Paradoxical drop in circulating neutrophil count following granulocyte-colony stimulating factor and stem cell factor administration in rhesus macaques.

PubMed

Gordon, Brent C; Revenis, Amy M; Bonifacino, Aylin C; Sander, William E; Metzger, Mark E; Krouse, Allen E; Usherson, Tatiana N; Donahue, Robert E

2007-06-01

Granulocyte colony-stimulating factor (G-CSF) is frequently used therapeutically to treat chronic or transient neutropenia and to mobilize hematopoietic stem cells. Shortly following G-CSF administration, we observed a dramatic transient drop in circulating neutrophil number. This article characterizes this effect in a rhesus macaque animal model. Hematologic changes were monitored following subcutaneous (SQ) administration of G-CSF. G-CSF was administered as a single SQ dose at 10 microg/kg or 50 microg/kg. It was also administered (10 microg/kg) in combination with stem cell factor (SCF; 200 microg/kg) over 5 days. Flow cytometry was performed on serial blood samples to detect changes in cell surface adhesion protein expression. Neutrophil count dramatically declined 30 minutes after G-CSF administration. This decline was observed whether 10 microg/kg G-CSF was administered in combination with SCF over 5 days, or given as a single 10 microg/kg dose. At a single 50 microg/kg dose, the decline accelerated to 15 minutes. Neutrophil count returned to baseline after 120 minutes and rapidly increased thereafter. An increase in CD11a and CD49d expression coincided with the drop in neutrophil count. A transient paradoxical decline in neutrophil count was observed following administration of G-CSF either alone or in combination with SCF. This decline accelerated with the administration of a higher dose of G-CSF and was associated with an increase in CD11a and CD49d expression. It remains to be determined whether this decline in circulating neutrophils is associated with an increase in endothelial margination and/or entrance into extravascular compartments.

Adherence to hepatitis A virus vaccination in HIV-infected men who have sex with men.

PubMed

Kourkounti, Sofia; Paparizos, Vassilios; Leuow, Kirsten; Paparizou, Eleni; Antoniou, Christina

2015-10-01

Although vaccination against hepatitis A virus (HAV) is essential for human immunodeficiency virus (HIV)-infected patients, the uptake of HAV vaccine is reported to be very low. From 2007 to 2012, 912 HIV-infected men in Athens, Greece were screened for exposure to HAV. Two doses of an HAV vaccine were recommended to 569 eligible patients. Reminder cards with scheduled vaccination visits were given to each patient. Among eligible patients, 62.2% (354/569) received both doses. Patients who were fully vaccinated compared with non-adherent patients were natives, older, had undetectable HIV viral load, higher CD4 T cell counts and lower nadir CD4 T cell counts. Multivariate logistic regression revealed that the patient's country of origin (p = 0.024; OR = 2.712; 95% CI, 1.139-6.457), CD4 T cell count (p < 0.001) and nadir CD4 T cell count (p < 0.001) were factors directly associated with adherence. In conclusion, adherence to HAV vaccination was better than in previously published data. Because many of the factors related to vaccination completion are parameters of HIV infection, it appears that physician interest in HIV care and vaccination planning is crucial to enhancing vaccine uptake. © The Author(s) 2015.

Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

PubMed

Dinges, D F; Douglas, S D; Zaugg, L; Campbell, D E; McMann, J M; Whitehouse, W G; Orne, E C; Kapoor, S C; Icaza, E; Orne, M T

1994-05-01

The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep.

Leukocytosis and natural killer cell function parallel neurobehavioral fatigue induced by 64 hours of sleep deprivation.

PubMed Central

Dinges, D F; Douglas, S D; Zaugg, L; Campbell, D E; McMann, J M; Whitehouse, W G; Orne, E C; Kapoor, S C; Icaza, E; Orne, M T

1994-01-01

The hypothesis that sleep deprivation depresses immune function was tested in 20 adults, selected on the basis of their normal blood chemistry, monitored in a laboratory for 7 d, and kept awake for 64 h. At 2200 h each day measurements were taken of total leukocytes (WBC), monocytes, granulocytes, lymphocytes, eosinophils, erythrocytes (RBC), B and T lymphocyte subsets, activated T cells, and natural killer (NK) subpopulations (CD56/CD8 dual-positive cells, CD16-positive cells, CD57-positive cells). Functional tests included NK cytotoxicity, lymphocyte stimulation with mitogens, and DNA analysis of cell cycle. Sleep loss was associated with leukocytosis and increased NK cell activity. At the maximum sleep deprivation, increases were observed in counts of WBC, granulocytes, monocytes, NK activity, and the proportion of lymphocytes in the S phase of the cell cycle. Changes in monocyte counts correlated with changes in other immune parameters. Counts of CD4, CD16, CD56, and CD57 lymphocytes declined after one night without sleep, whereas CD56 and CD57 counts increased after two nights. No changes were observed in other lymphocyte counts, in proliferative responses to mitogens, or in plasma levels of cortisol or adrenocorticotropin hormone. The physiologic leukocytosis and NK activity increases during deprivation were eliminated by recovery sleep in a manner parallel to neurobehavioral function, suggesting that the immune alterations may be associated with biological pressure for sleep. PMID:7910171

Only Follow-Up of Memory B Cells Helps Monitor Rituximab Administration to Patients with Neuromyelitis Optica Spectrum Disorders.

PubMed

Lebrun, Christine; Cohen, Mikael; Rosenthal-Allieri, Maria Alessandra; Bresch, Saskia; Benzaken, Sylvia; Marignier, Romain; Seitz-Polski, Barbara; Ticchioni, Michel

2018-06-07

Neuromyelitis optica spectrum disorders (NMOSD) are identified as a spectrum of inflammatory demyelinating disorders involving the brain, spinal cord and optic nerves. These disorders require early diagnosis and highly active immunosuppressive treatment. Rituximab (RTX) has demonstrated efficacy in limiting relapse in NMOSD when using several administration schedules. We questioned if the CD19+ CD27+ memory B cell count was a more reliable marker to monitor RTX administration than the RTX plasma level and CD19+ B cell count. We analyzed 125 blood samples from 17 NMOSD patients treated with RTX and also measured the level of anti-aquaporine-4 antibodies (anti-AQP-4 Abs), human anti-chimeric antibodies to the murine fragment of RTX (HACA-RTX Abs), and the RTX concentration. The mean follow-up time of the cohort was 7.4 (2-16) years. All patients improved with a mean EDSS going from 4 (1-8.5) to 2.7 (1-5.5). The mean interval between RTX infusions was 9.6 months with identification of prolonged responders. Total CD19+ B cell detection with the routine technique did not correlate to re-emergence of CD19+ CD27+ memory B cells. The RTX residual concentration did not correlate with the CD19+ CD27+ memory B cell count or with anti-RTX antibody production. In contrast to total CD19+ cell, detected with the routine technique, CD19+ CD27+ memory B cells are a reliable marker for biological relapse and allow a decrease in the frequency of infusions.

Expanding ART for Treatment and Prevention of HIV in South Africa: Estimated Cost and Cost-Effectiveness 2011-2050

PubMed Central

Granich, Reuben; Kahn, James G.; Bennett, Rod; Holmes, Charles B.; Garg, Navneet; Serenata, Celicia; Sabin, Miriam Lewis; Makhlouf-Obermeyer, Carla; De Filippo Mack, Christina; Williams, Phoebe; Jones, Louisa; Smyth, Caoimhe; Kutch, Kerry A.; Ying-Ru, Lo; Vitoria, Marco; Souteyrand, Yves; Crowley, Siobhan; Korenromp, Eline L.; Williams, Brian G.

2012-01-01

Background Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. Methods We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm3 (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses. Results Expanding ART to CD4 count <350 cells/mm3 prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. Conclusion Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated. PMID:22348000

Impact of Protein Supplementation and Care and Support on Body Composition and CD4 Count among HIV-Infected Women Living in Rural India: Results from a Randomized Pilot Clinical Trial

PubMed Central

Nyamathi, Adeline; Sinha, Sanjeev; Ganguly, Kalyan K; Ramakrishna, Padma; Suresh, P.; Carpenter, Catherine L

2013-01-01

Body composition in HIV-infected individuals is subject to many influences. We conducted a pilot six-month randomized trial of 68 WLA (women living with AIDS) from rural India. High protein intervention combined with education and supportive care delivered by HIV-trained village women (Asha [Activated Social Health Activist] Life [AL]) was compared to standard protein with usual care delivered by village community assistants (Usual Care [UC]). Measurements included CD4 counts, ART adherence, socio-demographics, disease characteristics (questionnaires); and anthropometry (bioimpedance analyzer). Repeated measures analysis of variance modeled associations. AL significantly gained in BMI, muscle mass, fat mass, ART adherence, and CD4 counts compared to UC, with higher weight and muscle mass gains among ART adherent (≥ 66%) participants who had healthier immunity (CD4 ≥ 450). BMI of WLA improved through high protein supplementation combined with education and supportive care. Future research is needed to determine which intervention aspect was most responsible. PMID:23370835

The Potentials of Fas Receptors and Ligands in Monitoring HIV-1 Disease in Children in Yaoundé, Cameroon.

PubMed

Ikomey, G; Assoumou, M-C Okomo; Atashili, J; Mesembe, M; Mukwele, B; Lyonga, E; Eyoh, A; Kafando, A; Ndumbe, P M

2016-09-01

Difficulties in systematically monitoring HIV viral load in resource-limited settings prompt the search for alternate approaches. The authors aimed at assessing the correlation between the plasma levels of soluble forms of Fas receptors (Fas) and Fas ligands (FasL) with standard indicators of HIV disease progression in children. Twenty-two HIV-1-positive children were enrolled in Yaounde. CD4 counts, CD4% counts, plasma levels of Fas, FasL, and HIV-1 RNA levels were assayed. The correlation coefficients (P values) between FasL levels and each of HIV-1 viral load, CD4 counts, and CD4% were, respectively, .56 (.01), -.29 (.18), and .30 (.18). On the other hand, the respective correlation coefficients (P values) with Fas levels were .12 (.60), -.30 (.18), and -.29 (.19). The significant correlation between levels of HIV-1 viral load and FasL suggests that the latter needs to be further studied as a potential biomarker to monitor HIV-1 disease progression in children in resource-limited setting. © The Author(s) 2013.

Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease.

PubMed

Chen, Fabian; Day, Sara L; Metcalfe, Russell A; Sethi, Gulshan; Kapembwa, Moses S; Brook, M Gary; Churchill, Duncan; de Ruiter, Annemiek; Robinson, Stephen; Lacey, Charles J; Weetman, Anthony P

2005-03-01

Experimental evidence from animal models has provided a framework for our current understanding of autoimmune disease pathogenesis and supports the importance of genetic predisposition, molecular mimicry, and immune dysregulation. However, only recently has evidence emerged to support the role of immune dysregulation in human organ-specific autoimmune disease. In the current study of the "late" manifestation of autoimmune thyroid disease (AITD) in a cohort of human immunodeficiency virus (HIV)-positive patients following highly active antiretroviral therapy (HAART), we discuss how immune dysregulation and factors associated with the immunopathology of HIV infection fit the current understanding of autoimmunity and provide a plausible basis for our clinical observations. De novo diagnoses of thyroid disease were identified between 1996 and 2002 in 7 HIV treatment centers (5/7 centers completed the study). Patients were diagnosed as clinical case entities and not discovered through thyroid function test screening. Paired plasma specimens were used to demonstrate sequential rise in thyroid antibodies. Seventeen patients were diagnosed with AITD (median age, 38 yr; 65% were of black African or black Caribbean ethnicity; and 82% were female). The median duration of immune reconstitution was 17 months. Graves disease (GD) was diagnosed in 15 of 17 patients. One patient developed hashithyrotoxicosis with atypically raised C-reactive protein, and another developed hypothyroidism. One GD patient had associated secondary hypoadrenalism. The estimated combined prevalence of GD for 4 treatment centers for female patients was 7/234 and for males was 2/1289. The denominator numbers were matched controls, from 4 centers able to provide data, who commenced HAART during the same time (January 1996 to July 2002) and who did not develop clinical AITD. The mean baseline pre-HAART CD4 count was 67 cells/mL, and the mean increase from nadir to AITD presentation was 355 cells/mL. AITD patients were more likely than controls (95% confidence interval, chi-square test) to be severely compromised at baseline (as defined by a CD4 count < 200 cells/mL or the presence of an acquired immunodeficiency syndrome [AIDS]-defining diagnosis), and to experience greater CD4 increments following HAART. AITD may be a late manifestation of immune reconstitution in HIV-positive patients taking HAART, and immune dysregulation may be an important factor.

Prevalence and risk factors of poor immune recovery among adult HIV patients attending care and treatment centre in northwestern Tanzania following the use of highly active antiretroviral therapy: a retrospective study.

PubMed

Gunda, Daniel W; Kilonzo, Semvua B; Kamugisha, Erasmus; Rauya, Engelbert Z; Mpondo, Bonaventura C

2017-06-08

Highly Active Antiretroviral therapy (HAART) reverses the effect of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) by durably suppressing viral replication. This allows CD4 gain to levels that are adequate enough to restore the body's capability to fight against opportunistic infections (OIs). Patients with poor immune recovery have been shown to have higher risk of developing both AIDS and non AIDS related clinical events. This study aimed at assessing the proportions and risk factors of poor immune recovery in adult HIV-infected patients on 48 months of HAART attending care and treatment center (CTC) in northwestern Tanzania. A retrospective analysis of adult HIV patients' data attending CTC at Sekou Toure hospital and who initiated HAART between February 2004 and January 2008 was done. Poor immune recovery was defined as a CD4 count less than 350 cells/µl on follow up as used in other studies. A total of 734 patients were included in the study. In this study 50.25% of patients attending CTC at Sekou Toure hospital were found to have poor immune recovery. The risk of developing inadequate immune recovery was independently associated with male gender, age older than 50 years, low baseline CD4 counts, and advanced World Health Organization (WHO) clinical stage. Poor immune recovery is prevalent among adult HIV patients attending CTC at Sekou Toure hospital in Northwestern part of Tanzania and opportunistic infections are common in this sub group of patients. Clinicians in resource limited countries need to identify these patients timely and plan them for targeted viral assessment and close clinical follow up to improve their long term clinical outcome.

Pilot study of once-daily simplification therapy with abacavir/lamivudine/zidovudine and efavirenz for treatment of HIV-1 infection.

PubMed

Ruane, Peter; Lang, Joseph; DeJesus, Edwin; Berger, Daniel S; Dretler, Robin; Rodriguez, Allan; Ward, Douglas J; Lim, Michael L; Liao, Qiming; Reddy, Sunila; Clair, Marty St; Vila, Tania; Shaefer, Mark S

2006-01-01

The purpose of this pilot study was to explore the efficacy and safety of the abacavir/lamivudine/zidovudine fixed-dose combination tablet administered as two tablets once daily (qd) versus one tablet twice daily (bid) in combination with efavirenz (EFV). This was a prospective, randomized, open-label, multicenter study with a 24-week treatment period in 7 outpatient HIV clinics in the United States. Patients currently receiving an initial regimen of abacavir/lamivudine/zidovudine bid plus EFV qd for at least 6 months with HIV-1 RNA <50 copies/mL for at least 3 months and a screening CD4+ cell count > or = 200 cells/mm3 were eligible. Thirty-six patients enrolled, and 35 (97%) completed the study. Participants were randomized to switch to 2 tablets of abacavir/lamivudine/zidovudine qd plus EFV qd (QD arm) or continue current treatment (BID arm) for 24 weeks. Efficacy, safety, and adherence were evaluated. Median baseline CD4+ cell count was 521 cells/mm3. At week 24, HIV-1 RNA <50 copies/mL was achieved for 94% of participants in the QD arm and 89% in the BID arm by intent-to-treat, missing = failure analysis (95% confidence interval for difference: > or = 0.29 to +0.18, p = 1.000). At week 24, median CD4+ cell count change from baseline was +26 cells/mm3 for the QD arm and -39 cells/mm3 for BID arm. One patient randomized to the QD arm met virologic failure criteria (confirmed HIV-1 RNA >120 copies/mL) at week 20 and viral genotype showed M184V. After failure, this patient revealed he never took EFV throughout the entire study after randomization, effectively receiving only abacavir/lamivudine/zidovudine qd alone. Median adherence was slightly higher in the QD arm, although both arms had broad variability and overlapping interquartile ranges. Adverse events were infrequent and occurred with similar frequency between arms; treatment-related adverse events were abdominal pain, flatulence, nausea, headache, and abnormal dreams (1 patient [3%] for each adverse event). No patients withdrew due to adverse events, and no abacavir hypersensitivity reactions were reported. In this pilot study of patients suppressed on abacavir/lamivudine/zidovudine bid plus EFV, 94% of participants switching to abacavir/lamivudine/zidovudine qd plus EFV maintained virologic suppression, compared to 89% of participants continuing abacavir/lamivudine/zidovudine bid plus EFV.

The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents

PubMed Central

STRAY-PEDERSEN, A; JÓNSSON, T; HEIBERG, A; LINDMAN, C R; WIDING, E; AABERGE, I S; BORRESEN-DALE, A L; ABRAHAMSEN, T G

2004-01-01

Eleven Norwegian patients (aged 2–33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0·23 (0·05–0·41) g/l versus 0·91 (0·58–1·26) g/l in the other patients (P = 0·002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0·9 (0·4–1·4) U/ml, while normal levels were found in their parents 11·1 (8·7–13·4) U/ml (P < 0·001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0·85, P = 0·001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23–64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype. PMID:15196260

Changes in estimated glomerular filtration rate over time in South African HIV-1-infected patients receiving tenofovir: a retrospective cohort study

PubMed Central

De Waal, Reneé; Cohen, Karen; Fox, Matthew P; Stinson, Kathryn; Maartens, Gary; Boulle, Andrew; Igumbor, Ehimario U; Davies, Mary-Ann

2017-01-01

Abstract Introduction: Tenofovir has been associated with decline in kidney function, but in patients with low baseline kidney function, improvements over time have been reported. Additionally, the magnitude and trajectory of estimated glomerular filtration rate (eGFR) changes may differ according to how eGFR is calculated. We described changes in eGFR over time, and the incidence of, and risk factors for, kidney toxicity, in a South African cohort. Methods: We included antiretroviral-naïve patients ≥16 years old who started tenofovir-containing antiretroviral therapy (ART) between 2002 and 2013. We calculated eGFR using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Cockcroft-Gault equations. We described changes in eGFR from ART initiation using linear mixed effects regression. We described the incidence of eGFR <30 mL/min on treatment, and identified associations with low eGFR using Cox regression. Results: We included 15156 patients with median age of 35.4 years (IQR 29.9–42.0), median CD4 cell count of 168 cells/µL (IQR 83–243), and median eGFR (MDRD) of 98.6 mL/min (IQR 84.4–115.6). Median duration of follow up on tenofovir was 12.9 months (IQR 5.1–23.3). Amongst those with a baseline and subsequent eGFR  available, mean eGFR change from baseline at 12 months was −4.4 mL/min (95% CI −4.9 to −4.0), −2.3 (−2.5 to −2.1), and 0.6 (0.04 to 1.2) in those with baseline eGFR ≥90 mL/min; and 11.9 mL/min (11.0 to 12.7), 14.6 (13.5 to 15.7), and 11.0 (10.3 to 11.7) in those with baseline eGFR <90 mL/min, according to the MDRD, CKD-EPI (n = 11 112), and Cockcroft-Gault (n = 9 283) equations, respectively. Overall, 292 (1.9%) patients developed eGFR <30 mL/min. Significant associations with low eGFR included older age, baseline eGFR <60 mL/min, CD4 count <200 cells/µL, body weight <60 kg, and concomitant protease inhibitor use. Conclusions: Patients on tenofovir with baseline eGFR ≥90 mL/min experienced small but significant declines in eGFR over time when eGFR was estimated using the MDRD or CKD-EPI equations. However, eGFR increased in patients with eGFR <90 mL/min, regardless of which estimating equation was used. Decreases to below 30 mL/min were uncommon. In settings with limited access to laboratory testing, monitoring guidelines should consider focusing on higher risk patients. PMID:28406595

CD28-Negative CD4+ and CD8+ T Cells in Antiretroviral Therapy–Naive HIV-Infected Adults Enrolled in Adult Clinical Trials Group Studies

PubMed Central

Tassiopoulos, Katherine; Landay, Alan; Collier, Ann C.; Connick, Elizabeth; Deeks, Steven G.; Hunt, Peter; Lewis, Dorothy E.; Wilson, Cara; Bosch, Ronald

2012-01-01

Background Individuals infected with human immunodeficiency virus (HIV) have higher risk than HIV-negative individuals for diseases associated with aging. T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks. Methods We measured the percentage of CD28−CD4+ and CD8+ T cells from HIV-infected treatment-naive adults from 5 Adult Clinical Trials Group (ACTG) antiretroviral therapy (ART) studies and the ALLRT (ACTG Longitudinal Linked Randomized Trials) cohort, and from 48 HIV-negative adults. Pretreatment and 96-week posttreatment %CD28− cells were assessed using linear regression for associations with age, sex, race/ethnicity, CD4 count, HIV RNA, ART regimen, and hepatitis C virus (HCV) infection. Results In total, 1291 chronically HIV-infected adults were studied. Pretreatment, lower CD4 count was associated with higher %CD28−CD4+ and %CD28−CD8+ cells. For CD8+ cells, younger age and HCV infection were associated with a lower %CD28−. ART reduced %CD28− levels at week 96 among virally suppressed individuals. Older age was strongly predictive of higher %CD28−CD8+. Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28−. Conclusions Effective ART reduced the proportion of CD28− T cells. However, levels remained abnormally high and closer to levels in older HIV-uninfected individuals. This finding may inform future research of increased rates of age-associated disease in HIV-infected adults. PMID:22448010

The CYP2B6 G516T polymorphism influences CD4+ T-cell counts in HIV-positive patients receiving antiretroviral therapy in an ethnically diverse region of the Amazon.

PubMed

Queiroz, Maria Alice Freitas; Laurentino, Rogério Valois; da Silva Graça Amoras, Ednelza; Araújo, Mauro Sérgio Moura de; Gomes, Samara Tatielle Monteiro; Lima, Sandra Souza; Vallinoto, Antonio Carlos Rosário; de Oliveira Guimarães Ishak, Marluísa; Ishak, Ricardo; Machado, Luiz Fernando Almeida

2017-02-01

Cytochrome P450 (CYP) enzyme polymorphisms seem to significantly influence the variability of the responses to certain antiretroviral drugs and their toxicity levels. The objective of this study was to evaluate the influence of the CYP2B6 G516T polymorphism on hepatic, renal, immunological, and viral marker changes in HIV-1-positive patients receiving treatment in an ethnically diverse region of the Amazon. CYP2B6 G516T genotyping was performed by real-time PCR (RT-PCR) in samples from 185 patients. Urea, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), CD4 + /CD8 + T-cell counts, and HIV-1 plasma viral load were measured. The polymorphic CYP2B6 G516T allele frequency was 0.36, which is different from the frequencies in other ethnic groups. The polymorphic genotype was associated with changes in the urea and ALT levels, although the median values were within the normal range. The TT genotype was also associated with significantly lower CD4 + T-cell counts in patients using efavirenz. The CYP2B6 G516T polymorphism seems to affect the response to efavirenz treatment by reducing CD4 + T-cell counts in patients with a high degree of miscegenation who use this antiretroviral agent. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Isolation and evaluation of Candida species and their association with CD4+ T cells counts in HIV patients with diarrhoea.

PubMed

Awoyeni, Ayobami; Olaniran, Olarinde; Odetoyin, Babatunde; Hassan-Olajokun, Rachel; Olopade, Bolatito; Afolayan, David; Adekunle, Oluwakayode

2017-06-01

Gastrointestinal infection is one of the most common infections among HIV patients. Candida spp have been implicated in the aetiology of chronic diarrhoea in HIV patients, but little is known about this in Nigeria. We determined the prevalence of faecal candidiasis in HIV patients in relation to diarrhoea, CD4 counts, and other socio-demographic factors and the spectrum of Candida isolates involved. One hundred and fifty four HIV patients were investigated. Candida species were identified by standard techniques. Socio-demographic and clinical information was obtained from the patients using a structured questionnaire. The CD4 count was estimated using a single platform flow cytometer. Candida overgrowth was detected in 61 (39.5%) HIV patients, and diarrhoea was associated with candidiasis in the subjects (P=0.001). Candidiasis was commonly detected among subjects in the 29-39 years' age group. A CD4 count below 200 cells/mm 2 (62.3%) was a risk factor for acquiring candidiasis among HIV patients (P=0.001). Candida albicans (65.6%) was the most frequently recovered species followed by Candida krusei (16.4%) and Candida tropicalis (14.8%). Candidiasis is an important opportunistic infection in HIV-patients in Ile-Ife. There is need for regular checks for opportunistic infections, including candidiasis in HIV patients to monitor disease progression and prevent subsequent complications.

Changing electrolyte and acido-basic profile in HIV-infected patients in the HAART era.

PubMed

Isnard Bagnis, Corinne; Du Montcel, Sophie Tezenas; Fonfrede, Michele; Jaudon, Marie Chantal; Thibault, Vincent; Carcelain, Guislaine; Valantin, Marc Antoine; Izzedine, Hassan; Servais, Aude; Katlama, Christine; Deray, Gilbert

2006-01-01

HIV-infected patients may develop a variety of underreported metabolic abnormalities that may be classified into HIVAN, specific HIV abnormalities, coincidental renal disorders and anti-retroviral-treatment-induced side effects. Our descriptive cross-sectional study evaluates the prevalence of electrolyte and acid base disorders in HIV patients in the HAART era in a tertiary care teaching hospital. All consecutive HIV-infected patients (n = 1,232) presenting at our Department of Infectious Disease over 3 months were included. All available biochemical data obtained at admission or on the day of the visit were analyzed. We identified risk factors for electrolyte and acid base disorders with univariate regression analysis and multivariate stepwise regression analysis. Variables tested for significance included age, sex, absolute CD4 and CD8 counts, hepatitis B and C antibodies, and use and type of anti-retroviral medication. Most frequent and clinically relevant abnormalities were hyperuricemia in 41.3%, hypophosphatemia in 17.2% and low bicarbonate level in 13.6% of HIV-tested patients. Plasma magnesium was out of the normal range in 38.9% and blood glucose in 25.3% of the tested patients. When CD4 count was below 200/mm3, 9.2% of tested patients experienced low serum calcium (vs. 0.5% if CD4 count >200/mm3, p < 0.002), 11.4% increased creatinine plasma level (vs. 2.3% if CD4 count >200/mm3, p < 0.0001) and 24.5% low serum bicarbonate (vs. 13.7% if CD4 count >200/mm3, p < 0.0001). Protease inhibitor treatment was a significant risk factor of hyperuricemia (p < 0.003). Non-nucleoside reverse transcriptase inhibitor therapy was significantly associated with less hyperuricemia (OR = 0.6, 95% CI 0.38-0.96) and with hypophosphatemia (OR = 2.0, 95% CI 1.1-3.4). The profile of biochemical abnormalities in HIV-infected patients has changed, hyperuricemia and hypophosphatemia being the most prevalent. Causes are poorly understood. Interpretation of drug-induced side effects in the HIV patient is only meaningful if performed versus a control group of patients. Copyright 2006 S. Karger AG, Basel

In utero and intra-partum HIV-1 transmission and acute HIV-1 infection during pregnancy: using the BED capture enzyme-immunoassay as a surrogate marker for acute infection.

PubMed

Marinda, Edmore T; Moulton, Lawrence H; Humphrey, Jean H; Hargrove, John W; Ntozini, Robert; Mutasa, Kuda; Levin, Jonathan

2011-08-01

The BED assay was developed to estimate the proportion of recent HIV infections in a population. We used the BED assay as a proxy for acute infection to quantify the associated risk of mother-to-child-transmission (MTCT) during pregnancy and delivery. Design A total of 3773 HIV-1 sero-positive women were tested within 96 h of delivery using the BED assay, and CD4 cell count measurements were taken. Mothers were classified according to their likelihood of having recently seroconverted. The risk of MTCT in utero and intra-partum was assessed comparing different groups defined by BED and CD4 cell count, adjusting for background factors using multinomial logistic models. Compared with women with BED ≥ 0.8/CD4 ≥ 350 (typical of HIV-1 chronic patients) there was insufficient evidence to conclude that women presenting with BED < 0.8/CD4 ≥ 350 (typical of recent infections) were more likely to transmit in utero [adjusted odds ratio (aOR) = 1.37, 96% confidence interval (CI) 0.90-2.08, P = 0.14], whereas women with BED < 0.8/CD4 200-349 (possibly recently infected patients) had a 2.57 (95% CI 1.39-4.77, P-value < 0.01) odds of transmitting in utero. Women who had BED < 0.8/CD4 < 200 were most likely to transmit in utero (aOR 3.73, 95% CI 1.27-10.96, P = 0.02). BED and CD4 cell count were not predictive of intra-partum infections. These data provide evidence that in utero transmission of HIV might be higher among women who seroconvert during pregnancy.

[Clinical characteristic and treatment of cytomegalovirus retinitis in 80 patients with acquired immunodeficiency syndrome].

PubMed

Yang, Yaling; Jiang, Rui; He, Taiwen; Lu, Hongzhou; Zhang, Renfang; Shen, Yinzhong; Zheng, Yufang; Liu, Li; Wang, Wenji

2014-03-01

To investigate the clinical characteristics of cytomegalovirus retinitis (CMVR) in acquired immunodeficiency syndrome (AIDS) patients. Retrospective case-series study. The clinical and laboratory data of 80 AIDS patients (118 eyes) with findings of CMVR were collected from Shanghai Public Health Clinical Center from December 2006 to December 2011. The relationship between CMVR and cellular immunity, the high risk factor, clinical characteristics, treatment and prognosis of CMVR were analyzed in this study. χ(2) test was used to check the incidence of CMVR in different CD4(+) T lymphocyte count groups. There was 80 AIDS patients (118 eyes) totally, 71 males and 9 females. Their age was from 18 to 60 years old, which mean value was (38 ± 10) years old. The incidence in the group of CD4(+) T lymphocyte count over 100 cells/µl was lower than the two groups of CD4(+) T lymphocyte count less than 100 cells/µl (χ(2) = 15.567, 32.469; P = 0.00,0.00). CD4(+) T lymphocyte count was always ranged from 0 to 141 cells/µl in CMVR patients. It was less than 50 cells/µl in 81.3% cases. In 10.0% AIDS patients, CMVR was the first manifestation. In 25% AIDS patients(26 eyes), lesions in retina was found by routine eye examination. In 54.2% patients, the best corrected visual acuity was less than 0.3. Retinal necrosis was involvement near the posterior pole in 62.5% CMVR patients. The visual acuity of 51 eyes was improved after treatment within 94.1% cases which were treated within 3 months. However, BCVA of 35 eyes decreased or with less change within 42.9% cases which were treated after symptoms appeared 3 months. The anti-CMV treatment included induction and maintenance of ganciclovir or foscarnet stopped when the CD4(+)T lymphocyte count was more than 150 cells/µl in 3 continuous months. 86.9% eyes were cured clinically. Retinal detachment, immune reconstitution uveitis and complicated cataract was found in 13.1%, 12.1% and 20.5% cases respectively. Optic atrophy occurred in 6 eyes. The visual acuity of 28.9% eyes was 0.05 or less, 71.3% of that caused by retinal detachment, cataract and optic atrophy. CD4(+) T lymphocyte count reduction is the risk factor for CMVR. HAART and anti-CMV therapy will cure the CMVR clinically.Routine eye examinations should be performed in all AIDS patients to get early diagnosis of CMVR or other opportunistic infections to avoid vision loss, especially in those CD4(+) T lymphocyte count lower than 100 cells/µl.

Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study.

PubMed

Cahn, Pedro; Rolón, María José; Figueroa, María Inés; Gun, Ana; Patterson, Patricia; Sued, Omar

2017-05-09

A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686-36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296-517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm 3 (IQR: 180-462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients. This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients. NCT02211482.

Increased Bone Marrow (BM) Plasma Level of Soluble CD30 and Correlations with BM Plasma Level of Interferon (IFN)-γ, CD4/CD8 T-Cell Ratio and Disease Severity in Aplastic Anemia

PubMed Central

Shi, Jun; Ge, Meili; Li, Xingxin; Shao, Yingqi; Yao, Jianfeng; Zheng, Yizhou

2014-01-01

Idiopathic aplastic anemia (AA) is an immune-mediated bone marrow failure syndrome. Immune abnormalities such as decreased lymphocyte counts, inverted CD4/CD8 T-cell ratio and increased IFN-γ-producing T cells have been found in AA. CD30, a surface protein belonging to the tumor necrosis factor receptor family and releasing from cell surface as a soluble form (sCD30) after activation, marks a subset of activated T cells secreting IFN-γ when exposed to allogeneic antigens. Our study found elevated BM plasma levels of sCD30 in patients with SAA, which were closely correlated with disease severity, including absolute lymphocyte count (ALC) and absolute netrophil count (ANC). We also noted that sCD30 levels were positively correlated with plasma IFN-γ levels and CD4/CD8 T-cell ratio in patients with SAA. In order to explain these phenomena, we stimulated T cells with alloantigen in vitro and found that CD30+ T cells were the major source of IFN-γ, and induced CD30+ T cells from patients with SAA produced significantly more IFN-γ than that from healthy individuals. In addition, increased proportion of CD8+ T cells in AA showed enhanced allogeneic response by the fact that they expressed more CD30 during allogeneic stimulation. sCD30 levels decreased in patients responded to immunosuppressive therapy. In conclusion, elevated BM plasma levels of sCD30 reflected the enhanced CD30+ T cell-mediated immune response in SAA. CD30 as a molecular marker that transiently expresses on IFN-γ-producing T cells, may participate in mediating bone marrow failure in AA, which also can facilitate our understanding of AA pathogenesis to identify new therapeutic targets. PMID:25383872

Dual R3R5 tropism characterizes cerebrospinal fluid HIV-1 isolates from individuals with high cerebrospinal fluid viral load.

PubMed

Karlsson, Ulf; Antonsson, Liselotte; Ljungberg, Bengt; Medstrand, Patrik; Esbjörnsson, Joakim; Jansson, Marianne; Gisslen, Magnus

2012-09-10

To study the use of major and alternative coreceptors by HIV-1 isolates obtained from paired plasma and cerebrospinal fluid (CSF) samples. Paired plasma and CSF isolates from HIV-1-infected individuals with varying clinical, virologic, and immunologic parameters were assessed for the ability to infect indicator cells expressing a panel of coreceptors with documented expression in the central nervous system (CNS). HIV-1 isolates obtained from plasma and CSF in 28 individuals with varying viral load, CD4 T-cell counts, and with or without AIDS-defining disease were analyzed for the ability to infect NP2.CD4 cells stably expressing a panel of HIV coreceptors (CCR5, CXCR4, CCR3, CXCR6, GPR1, APJ, ChemR23, RDC-1 or BLT1). All isolates from both plasma and CSF utilized CCR5 and/or CXCR4. However, the ability to use both CCR3 and CCR5 (R3R5) was more pronounced in CSF isolates and correlated with high CSF viral load and low CD4 T-cell count. Notably, four out of five CSF isolates of subtype C origin exhibited CXCR6 use, which coincided with high CSF viral load despite preserved CD4 T-cell counts. The use of other alternative coreceptors was less pronounced. Dual-tropic R3R5 HIV-1 isolates in CSF coincide with high CSF viral load and low CD4 T-cell counts. Frequent CXCR6 use by CSF-derived subtype C isolates indicates that subtype-specific differences in coreceptor use may exist that will not be acknowledged when assessing plasma virus isolates. The findings may also bare relevance for HIV-1 replication within the CNS, and consequently, for the neuropathogenesis of AIDS.

T-cell phenotype and function following a first cART regimen containing either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor in HIV-infected late presenters: results from a retrospective, ex vivo study.

PubMed

Tincati, Camilla; Savoldi, Alessia; Cannizzo, E Stefania; Bellistrì, Giusi M; Termini, Roberta; Garau, Marzia; Mancusi, Daniela; d'Arminio Monforte, Antonella; Marchetti, Giulia

2016-01-01

We aimed to comparatively assess darunavir/ritonavir (DRV/r) and efavirenz (EFV)-based first-line cART regimens in the reconstitution of T-cell phenotype and function in HIV-infected, late presenter subjects. Retrospective, ex vivo study on stored peripheral blood mononuclear cell samples of cART-naive, HIV-infected individuals with CD4(+) T-cell counts <50>250/µl upon cART initiation with either DRV/r or EFV as third drugs of standard antiretroviral regimens. CD4(+) and CD8(+) T-cell maturation (CCR7/CD45RA) and proliferation (Ki67), CD8(+) T-cell activation (CD38/HLA-DR) as well as HIV- and cytomegalovirus (CMV)-specific responses (CD4/CD8/IL-2/IFN-γ) were studied by flow cytometry at baseline (T0), T3, T6 and T12 months. Soluble inflammatory markers (IL-6 and sCD14) were measured in plasma at T0 and T12. Wilcoxon and Mann-Whitney tests were used for statistics. A total of 19 patients started DRV/r and 15 EFV. Both regimens accounted for suppression of the HIV RNA load (<40 copies/ml), reconstitution of absolute CD4(+) T-cells and CD4(+)/CD8(+) T-cell ratio. All study participants displayed a significant decrease of activated HLA-DR(+)CD38(+) CD8(+) T-cells at all study time points, yet no differences were found between study groups in T-cell activation and maturation phenotype. From a functional standpoint, only individuals receiving DRV/r displayed transitory recovery of HIV-specific IL-2(+)IFN-γ(-) CD4(+) T-cells (T3: P=0.006) and IL-2(-)IFN-γ(+) CD8(+) T-cells (T3: P=0.032). DRV/r- and EFV-based regimens have an equal effect on T-cell phenotype and function in HIV late presenters. A temporary restoration of HIV-specific T-cell immunity early in the course of therapy with DRV/r possibly implies a more effective control over HIV in the first months following a PI/r-based regimen, even at late stage of disease.

Maternal serum alpha-fetoprotein and human chorionic gonadotropin levels in women with human immunodeficiency virus.

PubMed

Gross, Susan; Castillo, Wilfrido; Crane, Marilyn; Espinosa, Bialines; Carter, Suzanne; DeVeaux, Richard; Salafia, Carolyn

2003-04-01

The purpose of this study was to establish whether there is a correlation between maternal serum genetic screen analyte results in pregnant women with human immunodeficiency virus and corresponding human immunodeficiency virus index values. Medical records of all pregnant women with human immunodeficiency virus who were delivered at Bronx Lebanon Hospital Center from January 2000 through December 2001 were reviewed for maternal serum screen results, viral load, CD4 counts and percent, antiretroviral therapy, opportunistic infections, substance abuse, and other demographic data. Statistical analysis was accomplished with the chi(2) test, Mann-Whitney U test, and Spearman rank correlation test, with a probability value of <.05 considered significant. Of the 98 women with human immunodeficiency virus who were delivered, 49 women (50%) had a maternal serum genetic screen available. Screened and unscreened women had similar severity of human immunodeficiency virus disease, CD4 count and percentage, and viral loads. Serum screen results showed elevations in maternal serum human chorionic gonadotropin (1.43 +/- 1.04 multiples of the median [MoM]; range, 0.2-5.2 MoM) and maternal serum alpha-fetoprotein (1.29 +/- 0.9 MoM; range, 0.5-3.3 MoM) compared with expected values in the general obstetric population. Maternal serum human chorionic gonadotropin was correlated inversely with CD4 count (P =.002) and CD4 percent (P <.0001). Maternal serum alpha-fetoprotein varied directly with viral load (P <.0001). Increasing maternal serum human chorionic gonadotropin and maternal serum alpha-fetoprotein levels in patients with human immunodeficiency virus are correlated with increasing viral load and decreasing CD4 counts.

Validation of Microcapillary Flow Cytometry for Community-Based CD4+ T Lymphocyte Enumeration in Remote Burkina Faso

PubMed Central

Renault, Cybèle A; Traore, Arouna; Machekano, Rhoderick N; Israelski, Dennis M

2010-01-01

Background: CD4+ T lymphocyte enumeration plays a critical role in the initiation and monitoring of HIV-infected patients on antiretroviral therapy. There is an urgent need for low-cost CD4+ enumeration technologies, particularly for use in dry, dusty climates characteristic of many small cities in Sub-Saharan Africa. Design: Cross-sectional study. Methods: Blood samples from 98 HIV-infected patients followed in a community HIV clinic in Ouahigouya, Burkina Faso were obtained for routine CD4+ T lymphocyte count monitoring. The blood samples were divided into two aliquots, on which parallel CD4+ measurements were performed using microcapillary (Guava EasyCD4) and dedicated (Becton Dickinson FACSCount) CD4+ enumeration systems. Spearman rank correlation coefficient was calculated, and the sensitivity, specificity and positive predictive value (PPV) for EasyCD4 <200 cells/µL were determined compared to the reference standard FACSCount CD4 <200 cells/µL. Results: Mean CD4 counts for the EasyCD4 and FACSCount were 313.75 cells/µL and 303.47 cells/µL, respectively. The Spearman rank correlation coefficient was 0.92 (p<0.001). Median values using EasyCD4 were higher than those with the FACSCount (p=0.004). For a CD4<350 cells/uL, sensitivity of the EasyCD4 was 93.9% (95%CI 85.2-98.3%), specificity was 90.6% (95% CI 75.0-98.0%), and PPV was 95.4% (95%CI 87.1-99.0%). Conclusion: Use of the EasyCD4 system was feasible and highly accurate in the harsh conditions of this remote city in Sub-Saharan Africa, demonstrating acceptable sensitivity and specificity compared to a standard operating system. Microcapillary flow cytometry offers a cost-effective alternative for community-based, point-of-care CD4+ testing and could play a substantial role in scaling up HIV care in remote, resource-limited settings. PMID:21253463

CD4+ T Lymphocytes count in sickle cell anaemia patients attending a tertiary hospital.

PubMed

Ojo, Omotola Toyin; Shokunbi, Wuraola Adebola

2014-05-01

Sickle cell haemoglobin (HbS) is the commonest abnormal haemoglobin and it has a worldwide distribution. Reports have shown that patients with sickle cell anaemia (HbSS) have an increased susceptibility to infection leading to increased morbidity and mortality. Impaired leucocyte function and loss of both humoral and cell-mediated immunity are some of the mechanisms that have been reported to account for the immunocompromised state in patients with sickle cell disease. This study was carried out to determine the CD4+ T lymphocytes count in patients with sickle cell anaemia. A comparative cross-sectional study of 40 sickle cell anaemia patients in steady state (asymptomatic for at least 4 weeks) attending haematology clinic and 40 age and sex-matched healthy HbA control were recruited into the study. Both HbS patients and the controls were HIV negative. The blood samples obtained were analyzed for CD4+ T cell by Flow cytometry. The study found that there was no significant difference in the number of CD4+ T lymphocyte count between individuals with sickle cell anaemia and HbA (1016 ± 513 cells/μL vs 920 ± 364cells/μL). It is recommended that the functionality of CD4+ T lymphocyte should be considered rather than the number in further attempt to elucidate the cellular immune dysfunction in patients with sickle cell anaemia.

Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

PubMed Central

Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

2013-01-01

Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. Trial Registration isrctn.org Identifier: ISRCTN30019040 PMID:22820788

Treatment outcomes of HIV-positive patients on first-line antiretroviral therapy in private versus public HIV clinics in Johannesburg, South Africa.

PubMed

Moyo, Faith; Chasela, Charles; Brennan, Alana T; Ebrahim, Osman; Sanne, Ian M; Long, Lawrence; Evans, Denise

2016-01-01

Despite the widely documented success of antiretroviral therapy (ART), stakeholders continue to face the challenges of poor HIV treatment outcomes. While many studies have investigated patient-level causes of poor treatment outcomes, data on the effect of health systems on ART outcomes are scarce. We compare treatment outcomes among patients receiving HIV care and treatment at a public and private HIV clinic in Johannesburg, South Africa. This was a retrospective cohort analysis of ART naïve adults (≥18.0 years), initiating ART at a public or private clinic in Johannesburg between July 01, 2007 and December 31, 2012. Cox proportional-hazards regression was used to identify baseline predictors of mortality and loss to follow-up (>3 months late for the last scheduled visit). Generalized estimating equations were used to determine predictors of failure to suppress viral load (≥400 copies/mL) while the Wilcoxon rank-sum test was used to compare the median absolute change in CD4 count from baseline to 12 months post-ART initiation. 12,865 patients initiated ART at the public clinic compared to 610 at the private clinic. The patients were similar in terms of sex and age at initiation. Compared to public clinic patients, private clinic patients initiated ART at higher median CD4 counts (159 vs 113 cells/mm(3)) and World Health Organization stage I/II (76.1% vs 58.5%). Adjusted hazard models showed that compared to public clinic patients, private clinic patients were less likely to die (adjusted hazard ratio [aHR] 0.50; 95% confidence interval [CI] 0.35-0.70) but were at increased risk of loss to follow-up (aHR 1.80; 95% CI 1.59-2.03). By 12 months post-ART initiation, private clinic patients were less likely to have a detectable viral load (adjusted relative risk 0.65; 95% CI 0.49-0.88) and recorded higher median CD4 change from baseline (184 cells/mm(3) interquartile range 101-300 vs 158 cells/mm(3) interquartile range 91-244), when compared to public clinic patients. We identified differences in treatment outcomes between the two HIV clinics. Findings suggest that the type of clinic at which ART patients initiate and receive treatment can have an impact on treatment outcomes. Further research is necessary to provide more conclusive results.

Endothelial Progenitor Cells (EPC) Count by Multicolor Flow Cytometry in Healthy Individuals and Diabetes Mellitus (DM) Patients.

PubMed

Falay, Mesude; Aktas, Server

2016-11-01

The present study aimed to determine circulating Endothelial Progenitor Cell (EPC) counts by multicolor flow cytometry in healthy individuals and diabetic subjects by means of forming an analysis procedure using a combination of monoclonal antibodies (moAbs), which would correctly detect the circulating EPC count. The circulating EPC count was detected in 40 healthy individuals (20 Female, 20 Male; age range: 26 - 50 years) and 30 Diabetes Mellitus (DM) patients (15 Female, 15 Male; age range: 42 - 55) by multicolor flow cytometry (FCM) in a single-tube panel consisting of 5 CD45/CD31/CD34/CD309/ SYTO® and 16 monoclonal antibodies. Circulating EPC count was 11.33 (7.89 - 15.25) cells/µL in the healthy control group and 4.80 (0.70 - 10.85) cells/µL in the DM group. EPC counts were significantly lower in DM cases that developed coronary artery disease (53.3%) as compared to those that did not (p < 0.001). In the present study, we describe a method that identifies circulating EPC counts by multicolor flow cytometry in a single tube and determines the circulating EPC count in healthy individuals. This is the first study conducted on EPC count in Turkish population. We think that the EPC count found in the present study will be a guide for future studies.

Involvement of selenoprotein P and GPx4 gene expression in cadmium-induced testicular pathophysiology in rat.

PubMed

Messaoudi, Imed; Banni, Mohamed; Saïd, Lamia; Saïd, Khaled; Kerkeni, Abdelhamid

2010-10-06

To investigate the effect of co-exposure to cadmium (Cd) and selenium (Se) on selenoprotein P (SelP) and phospholipid hydroperoxide glutathione peroxidase (GPx4) gene expression in testis and to evaluate their possible involvement in Cd-induced testicular pathophysiology, male rats received either tap water, Cd or Cd+Se in their drinking water for 5 weeks. Cd exposure caused a down-regulation of SelP and GPx4 gene expression and a significant decrease in plasma and testicular concentrations of Se. These changes were accompanied by decreased plasma testosterone level, sperm count and motility, GSH content, protein-bound sulfhydryl concentration (PSH), enzymatic activities of catalase (CAT) and glutathione peroxidase (GSH-Px) as well as by increased glutathione-S-transferase (GST) activity, lipid peroxidation (as malondialdehyde, MDA) and proteins carbonyls (PC). The decrease of testicular SelP and GPx4 gene expression under Cd influence was significantly restored in Cd+Se group. Co-treatment with Cd and Se also totally reversed the Cd-induced depletion of Se, decrease in plasma testosterone level and partially restored Cd-induced oxidative stress and decrease in sperm count and motility. Taken together, these data suggest that down-regulation of SelP and GPx4 gene expression induces plasma and testicular Se depletion leading, at least in part, to Cd-induced testicular pathophysiology. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Site-specific differences in T cell frequencies and phenotypes in the blood and gut of HIV-uninfected and ART-treated HIV+ adults.

PubMed

Yukl, Steven A; Shergill, Amandeep K; Girling, Valerie; Li, Qingsheng; Killian, Maudi; Epling, Lorrie; Li, Peilin; Kaiser, Philipp; Haase, Ashley; Havlir, Diane V; McQuaid, Kenneth; Sinclair, Elizabeth; Wong, Joseph K

2015-01-01

Gastrointestinal T lymphocytes are critical for mucosal immunity and HIV pathogenesis, yet little is known about normal T cell numbers and phenotypes in different regions of the gut, or the degree to which ART can restore levels to those of HIV-uninfected individuals. To investigate these questions, we measured T cell frequencies and markers of memory, activation, anergy, and homing in the blood, ileum, and rectum of HIV- and ART-suppressed HIV+ adults. In HIV- individuals, T cell frequencies and phenotypes differed significantly between sites. Compared to HIV- adults, HIV+ adults had lower absolute CD4+T cell counts in the ileal lamina propria and lower relative CD4+T cell counts in the blood and ileum. In the gut, HIV+ adults had a higher proportion of CD38+ CD4+T cells, a lower proportion of terminally-differentiated effector cells, and, in the rectum, a higher proportion of CTLA-4+ CD4+T cells. In HIV+ individuals, relative CD4+T cell numbers in the ileum correlated with the proportion of CTLA-4+ CD4+T cells, whereas in the rectum, they tended to correlate with the proportion of circulating CD4+T cells expressing α4β7 or CCR6. Mechanisms of T cell reconstitution may differ throughout the gut, with homing contributing more in the rectum while ileal reconstitution is associated with mucosal CD4+T cell anergy.

Qualitative Immune Modulation by Interleukin-2 (IL-2) Adjuvant Therapy in Immunological Non Responder HIV-Infected Patients

PubMed Central

Sabbatini, Francesca; Bandera, Alessandra; Ferrario, Giulio; Trabattoni, Daria; Marchetti, Giulia; Franzetti, Fabio; Clerici, Mario; Gori, Andrea

2010-01-01

Background Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs). Methods and Findings PBMC from 12 immunological non-responders (INRs) (CD4+<200/µl, HIV-RNA<50 cp/ml) on combination antiretroviral treatment (cART) were collected at baseline, and after 3 IL-2 cycles. Eight INRs receiving only cART were studied as controls. After 21 days of PBMC incubation with a virulent M. avium suspension, counts of residual colony forming units (CFUs) and concentrations of TNF-α, IL-10 and IFN-γ were determined. In IL-2 treated patients, a significant reduction in mean residual CFUs of PBMC cultures was observed (p<0.01). Moreover, following IL-2 treatment, significant increases in PBMC's IFNγ production (p = 0.02) and substantial reductions in IL-10 levels were observed. Conclusions IL-2 therapy restores the ability of the lympho-monocyte system in eliciting an effective response against mycobacterial infections. Our data indicate the possibility of a clinical role held by IL-2 in enhancing the immune function of subjects unable to achieve immune competence through cART alone. PMID:21124762

Morphologic changes in the placentas of HIV-positive women and their association with degree of immune suppression.

PubMed

Vermaak, Anine; Theron, Gerhard B; Schubert, Pawel T; Kidd, Martin; Rabie, Ursula; Adjiba, Benedict M; Wright, Colleen A

2012-12-01

To provide baseline information regarding a possible association between specific histopathologic features of the placentas of HIV-positive women and the degree of immune suppression. A prospective single-blinded laboratory-based pilot study was conducted at Tygerberg Hospital, South Africa. The macroscopic and microscopic features of placentas from HIV-positive (n=91) and HIV-negative women (n=89) were compared and recorded using a standard template. Investigators were blinded to the participants' HIV status and CD4-positive cell count. Placentas from the HIV-positive group were characterized by decreased weight and increased number of marginal infarcts relative to the HIV-negative group. The most important microscopic finding was the increased presence of villitis of unknown etiology (VUE) among the group of untreated HIV-positive women with CD4 cell counts of 200 cells/mm(3) or below. Both macroscopic and microscopic differences relating to the degree of immune suppression were identified, which seemingly contradicts previous reports. Larger studies are warranted to define the function of antiretroviral therapy and VUE in the mechanism of mother-to-fetus transmission of HIV. Furthermore, the potential role of VUE in the pathophysiology of the compromised immune response observed among HIV-exposed but uninfected infants should be investigated. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.