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.

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.

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

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

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.

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

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

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

Incomplete Recovery of CD4 count, CD4 Percentage, and CD4/CD8 ratio in HIV-Infected Patients on Long-Term Antiretroviral Therapy with Suppressed Viremia.

PubMed

Mutoh, Yoshikazu; Nishijima, Takeshi; Inaba, Yosuke; Tanaka, Noriko; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

2018-03-02

The extent and duration of long-term recovery of CD4 count, CD4%, and CD4/CD8 ratio after initiation of combination antiretroviral therapy (cART) in patients with suppressed viral load are largely unknown. HIV-1 infected patients who started cART between January 2004 and January 2012 and showed persistent viral suppression (<200 copies/mL) for at least 4 years were followed up at AIDS Clinical Center, Tokyo. Change point analysis was used to determine the time point where CD4 count recovery shows a plateau, and linear mixed model was applied to estimate CD4 count at the change point. Data of 752 patients were analyzed [93% males, median age 38, median baseline CD4 count 172/µL (IQR, 62-253), CD4% 13.8% (IQR, 7.7-18.5), and CD4/8 ratio 0.23 (IQR, 0.12-0.35)]. The median follow-up period was 81.2 months and 91 (12.1%) patients were followed for >10 years. Change point analysis showed that CD4 count, CD4%, and CD4/CD8 ratio, continued to increase until 78.6, 62.2, and 64.3 months, respectively, with adjusted mean of 590 /µL (95%CI 572-608), 29.5% (29-30.1), and 0.89 (0.86-0.93), respectively, at the change point. Although 73.8% of the study patients achieved CD4 count ≥500 /μL, 48.2% of the patients with baseline CD4 count <100 /μL did not achieve CD4 count ≥500 /μL. Neither CD4% nor CD4/CD8 ratio normalized in a majority of patients. The results showed lack of normalization of CD4 count, CD4%, and CD4/CD8 ratio to the levels seen in healthy individuals even after long-term successful cART in patients with suppressed viral load.

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

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.

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

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.

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.

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.

Clinical Predictors of Immune Reconstitution following Combination Antiretroviral Therapy in Patients from the Australian HIV Observational Database

PubMed Central

Rajasuriar, Reena; Gouillou, Maelenn; Spelman, Tim; Read, Tim; Hoy, Jennifer; Law, Matthew; Cameron, Paul U.; Petoumenos, Kathy; Lewin, Sharon R.

2011-01-01

Background A small but significant number of patients do not achieve CD4 T-cell counts >500cells/µl despite years of suppressive cART. These patients remain at risk of AIDS and non-AIDS defining illnesses. The aim of this study was to identify clinical factors associated with CD4 T-cell recovery following long-term cART. Methods Patients with the following inclusion criteria were selected from the Australian HIV Observational Database (AHOD): cART as their first regimen initiated at CD4 T-cell count <500cells/µl, HIV RNA<500copies/ml after 6 months of cART and sustained for at least 12 months. The Cox proportional hazards model was used to identify determinants associated with time to achieve CD4 T-cell counts >500cells/µl and >200cells/µl. Results 501 patients were eligible for inclusion from AHOD (n = 2853). The median (IQR) age and baseline CD4 T-cell counts were 39 (32–47) years and 236 (130–350) cells/µl, respectively. A major strength of this study is the long follow-up duration, median (IQR) = 6.5(3–10) years. Most patients (80%) achieved CD4 T-cell counts >500cells/µl, but in 8%, this took >5 years. Among the patients who failed to reach a CD4 T-cell count >500cells/µl, 16% received cART for >10 years. In a multivariate analysis, faster time to achieve a CD4 T-cell count >500cells/µl was associated with higher baseline CD4 T-cell counts (p<0.001), younger age (p = 0.019) and treatment initiation with a protease inhibitor (PI)-based regimen (vs. non-nucleoside reverse transcriptase inhibitor, NNRTI; p = 0.043). Factors associated with achieving CD4 T-cell counts >200cells/µl included higher baseline CD4 T-cell count (p<0.001), not having a prior AIDS-defining illness (p = 0.018) and higher baseline HIV RNA (p<0.001). Conclusion The time taken to achieve a CD4 T-cell count >500cells/µl despite long-term cART is prolonged in a subset of patients in AHOD. Starting cART early with a PI-based regimen (vs. NNRTI-based regimen) is associated with more rapid recovery of a CD4 T-cell count >500cells/µl. PMID:21674057

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

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.).

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.

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

Evaluation of Baseline CD4+ T Cell Counts and ART Requirement in Newly Diagnosed HIV Seropositive Individuals in a Tertiary Care Hospital of Northern India.

PubMed

Bhattar, Sonali; Mehra, Bhanu; Bhalla, Preena; Rawat, Deepti

2016-11-01

Antiretroviral Therapy (ART) has changed the outlook of Human Immune-deficiency Virus (HIV)/Acquired Immuno Deficiency Syndrome (AIDS) patients worldwide. To analyse the trends in baseline CD4+ T cell counts and ART requirements in newly diagnosed HIV seropositive individuals in a Tertiary care hospital of Northern India. Out of 1263 HIV seropositive clients identified from January 2012 to June 2014, the baseline CD4+ T cell counts of only those 470 clients were analysed, who registered at the linked ART centre. The mean baseline CD4+ count of the study group was 249.77±216.0cells/mm 3 and that of male and female were 300.31±240.47cells/mm 3 and 232.38±204.25cells/mm 3 respectively. A total of 259 of 334 (77.54%) HIV reactive males, 83 of 130 (63.85%) HIV reactive females and overall 348 of 470 (74.04%) required antiretroviral treatment on enrolment. In the present study, about three-fourth of newly diagnosed HIV positive Indian patients required initiation of ART at registration. The relatively low baseline CD4+ T cell counts in this population highlights the need for timely baseline CD4+ counts testing of HIV positive patients and the urgency of initiating treatment in HIV reactive individuals in Indian health care settings.

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.

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

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

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.

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.

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

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

Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

PubMed

Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

2009-03-01

To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1 infected, Treatment-Naïve Subjects

PubMed Central

Skowron, Gail; Spritzler, John G.; Weidler, Jodi; Robbins, Gregory K.; Johnson, Victoria A.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Lie, Yolanda; Bates, Michael; Pollard, Richard B.

2012-01-01

Objectives To evaluate the association between baseline (BL) replication capacity (RC) [RCBL] and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1 infected subjects initiating antiretroviral therapy. Methods RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naïve subjects from ACTG384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Results Higher RCBL was associated with lower baseline CD4 (CD4BL) (r=−0.23, p<0.0001), higher baseline HIV-1 (RNABL) (r=0.25, p<0.0001), higher CD4BL activation percent (r=0.23, p<0.0001) and lower CD4BL memory count (r=−0.21, p=0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL naive percent (p=0.004, p=0.015, respectively). The interaction between CD4BL and RCBL was significant (p=0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL, and a negative association at lower absCD4BL. Conclusions At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different baseline CD4 counts. PMID:19194319

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

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

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.

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.

Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children aged 1–5 Years: A Causal Modelling Analysis

PubMed Central

Schomaker, Michael; Davies, Mary-Ann; Malateste, Karen; Renner, Lorna; Sawry, Shobna; N’Gbeche, Sylvie; Technau, Karl-Günter; Eboua, François; Tanser, Frank; Sygnaté-Sy, Haby; Phiri, Sam; Amorissani-Folquet, Madeleine; Cox, Vivian; Koueta, Fla; Chimbete, Cleophas; Lawson-Evi, Annette; Giddy, Janet; Amani-Bosse, Clarisse; Wood, Robin; Egger, Matthias; Leroy, Valeriane

2017-01-01

Background There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modelling analysis in children aged 1–5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups and regions. Methods ART-naïve children of age 12–59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation. Results About one quarter of the 5826 included children was from West Africa (24.6%). The median (first; third quartile) CD4% at the first visit was 16% (11%;23%), the median weight-for-age z-scores and height-for-age z-scores were −1.5 (−2.7; −0.6) and −2.5 (−3.5; −1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count<750 cells/mm3 or CD4%<25% was 0.2% (95%CI: −0.2%;0.3%), and the difference in the mean height-for-age z-scores of those who survived was −0.02 (95%CI: −0.04;0.01). Younger children aged 1–2 and children in West Africa had worse outcomes. Conclusions Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, though we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below750/25%. PMID:26479876

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.

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.

Improved survival in HIV treatment programs in Asia

PubMed Central

De La Mata, Nicole L; Kumarasamy, Nagalingeswaran; Khol, Vohith; Ng, Oon Tek; Van Nguyen, Kinh; Merati, Tuti Parwati; Pham, Thuy Thanh; Lee, Man Po; Durier, Nicolas; Law, Matthew

2016-01-01

Background Antiretroviral treatment (ART) for HIV-positive patients has expanded rapidly in Asia over the last ten years. Our study aimed to describe the time trends and risk factors for overall survival in patients receiving first-line ART in Asia. Methods We included HIV-positive adult patients who initiated ART between 2003–2013 (n=16 546), from seven sites across six Asia-Pacific countries. Patient follow-up was to May 2014. We compared survival for each country and overall by time period of ART initiation using Kaplan-Meier curves. Factors associated with mortality were assessed using Cox regression, stratified by site. We also summarized first-line ART regimens, CD4 count at ART initiation, and CD4 and HIV viral load testing frequencies. Results There were 880 deaths observed over 54 532 person-years of follow-up, a crude rate of 1.61 (1.51, 1.72) per 100 person-years. Survival significantly improved in more recent years of ART initiation. The survival probabilities at 4 years follow-up for those initiating ART in 2003–05 was 92.1%, 2006–09 was 94.3% and 2010–2013 was 94.5% (p<0.001). Factors associated with higher mortality risk included initiating ART in earlier time periods, older age, male sex, injecting drug use as HIV exposure and lower pre-ART CD4 count. Concurrent with improved survival was increased tenofovir use, ART initiation at higher CD4 counts, and greater monitoring of CD4 and HIV viral load. Conclusions Our results suggest that HIV-positive patients from Asia have improved survival in more recent years of ART initiation. This is likely a consequence of improvements in treatment and, patient management and monitoring over time. PMID:26961354

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.

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.

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.

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

Pre-cART Elevation of CRP and CD4+ T-Cell Immune Activation Associated With HIV Clinical Progression in a Multinational Case-Cohort Study.

PubMed

Balagopal, Ashwin; Asmuth, David M; Yang, Wei-Teng; Campbell, Thomas B; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R; Lalloo, Umesh G; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B; Semba, Richard D; Thomas, David L; Bollinger, Robert C; Gupta, Amita

2015-10-01

Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore, some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. A case-cohort study (n = 470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings clinical trial (1571 HIV treatment-naive adults who initiated cART; CD4 T-cell count <300 cells/mm; 9 countries) was conducted. A subcohort of 30 participants per country was randomly selected; additional cases were added from the main cohort. Cases [n = 236 (random subcohort 36; main cohort 200)] had clinical progression (incident WHO stage 3/4 event or death) within 96 weeks after cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4 T-cell count was 167 cells per cubic millimeter. In multivariate analysis, highest quartile C-reactive protein concentration [adjusted hazard ratio (aHR), 2.53; 95% confidence interval (CI): 1.02 to 6.28] and CD4 T-cell activation (aHR, 5.18; 95% CI: 1.09 to 24.47) were associated with primary outcomes, compared with lowest quartiles. sCD14 had a trend toward association with clinical failure (aHR, 2.24; 95% CI: 0.96 to 5.21). Measuring C-reactive protein and CD4 T-cell activation may identify patients with CD4 T-cell counts <300 cells per cubic millimeter at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART.

Pre-cART Elevation of CRP and CD4+ T-cell Immune Activation Associated with HIV Clinical Progression in a Multinational Case-Cohort Study

PubMed Central

Balagopal, Ashwin; Asmuth, David M.; Yang, Wei-Teng; Campbell, Thomas B.; Gupte, Nikhil; Smeaton, Laura; Kanyama, Cecilia; Grinsztejn, Beatriz; Santos, Breno; Supparatpinyo, Khuanchai; Badal-Faesen, Sharlaa; Lama, Javier R.; Lalloo, Umesh G.; Zulu, Fatima; Pawar, Jyoti S; Riviere, Cynthia; Kumarasamy, Nagalingeswaran; Hakim, James; Li, Xiao-Dong; Pollard, Richard B.; Semba, Richard D.; Thomas, David L.; Bollinger, Robert C.; Gupta, Amita

2015-01-01

Background Despite the success of combination antiretroviral therapy (cART), a subset of HIV-infected patients who initiate cART develop early clinical progression to AIDS; therefore some cART initiators are not fully benefitted by cART. Immune activation pre-cART may predict clinical progression in cART initiators. Methods A case-cohort study (n=470) within the multinational Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) clinical trial (1571 HIV treatment-naïve adults who initiated cART; CD4+ T cell count <300 cells/mm3; nine countries) was conducted. A subcohort of 30 participants/country was randomly selected; additional cases were added from the main cohort. Cases (n=236 [random subcohort–36; main cohort–200]) had clinical progression (incident WHO Stage 3/4 event or death) within 96 weeks following cART initiation. Immune activation biomarkers were quantified pre-cART. Associations between biomarkers and clinical progression were examined using weighted multivariable Cox-proportional hazards models. Results Median age was 35 years, 45% were women, 49% black, 31% Asian, and 9% white. Median CD4+ T-cell count was 167 cells/mm3. In multivariate analysis, highest quartile CRP concentration (adjusted hazards ratio [aHR] 2.53, 95%CI 1.02-6.28) and CD4+ T-cell activation (aHR 5.18, 95CI 1.09-24.47) were associated with primary outcomes, compared to lowest quartiles. sCD14 had a trend towards association with clinical failure (aHR 2.24, 95%CI 0.96–5.21). Conclusions Measuring CRP and CD4+ T-cell activation may identify patients with CD4+ T cell counts < 300 cells/mm3 at risk for early clinical progression when initiating cART. Additional vigilance and symptom-based screening may be required in this subset of patients even after beginning cART. PMID:26017661

Time to ART Initiation among Patients Treated for Rifampicin-Resistant Tuberculosis in Khayelitsha, South Africa: Impact on Mortality and Treatment Success.

PubMed

Daniels, Johnny Flippie; Khogali, Mohammed; Mohr, Erika; Cox, Vivian; Moyo, Sizulu; Edginton, Mary; Hinderaker, Sven Gudmund; Meintjes, Graeme; Hughes, Jennifer; De Azevedo, Virginia; van Cutsem, Gilles; Cox, Helen Suzanne

2015-01-01

Khayelitsha, South Africa, with high burdens of rifampicin-resistant tuberculosis (RR-TB) and HIV co-infection. To describe time to antiretroviral treatment (ART) initiation among HIV-infected RR-TB patients initiating RR-TB treatment and to assess the association between time to ART initiation and treatment outcomes. A retrospective cohort study of patients with RR-TB and HIV co-infection not on ART at RR-TB treatment initiation. Of the 696 RR-TB and HIV-infected patients initiated on RR-TB treatment between 2009 and 2013, 303 (44%) were not on ART when RR-TB treatment was initiated. The median CD4 cell count was 126 cells/mm3. Overall 257 (85%) patients started ART during RR-TB treatment, 33 (11%) within 2 weeks, 152 (50%) between 2-8 weeks and 72 (24%) after 8 weeks. Of the 46 (15%) who never started ART, 10 (21%) died or stopped RR-TB treatment within 4 weeks and 16 (37%) had at least 4 months of RR-TB treatment. Treatment success and mortality during treatment did not vary by time to ART initiation: treatment success was 41%, 43%, and 50% among patients who started ART within 2 weeks, between 2-8 weeks, and after 8 weeks (p = 0.62), while mortality was 21%, 13% and 15% respectively (p = 0.57). Mortality was associated with never receiving ART (adjusted hazard ratio (aHR) 6.0, CI 2.1-18.1), CD4 count ≤100 (aHR 2.1, CI 1.0-4.5), and multidrug-resistant tuberculosis (MDR-TB) with second-line resistance (aHR 2.5, CI 1.1-5.4). Despite wide variation in time to ART initiation among RR-TB patients, no differences in mortality or treatment success were observed. However, a significant proportion of patients did not initiate ART despite receiving >4 months of RR-TB treatment. Programmatic priorities should focus on ensuring all patients with RR-TB/HIV co-infection initiate ART regardless of CD4 count, with special attention for patients with CD4 counts ≤ 100 to initiate ART as soon as possible after RR-TB treatment initiation.

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.

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.

The Impact of Implementation Fidelity on Mortality Under a CD4-Stratified Timing Strategy for Antiretroviral Therapy in Patients With Tuberculosis.

PubMed

Patel, Monita R; Westreich, Daniel; Yotebieng, Marcel; Nana, Mbonze; Eron, Joseph J; Behets, Frieda; Van Rie, Annelies

2015-05-01

Among patients with tuberculosis and human immunodeficiency virus type 1, CD4-stratified initiation of antiretroviral therapy (ART) is recommended, with earlier ART in those with low CD4 counts. However, the impact of implementation fidelity to this recommendation is unknown. We examined a prospective cohort study of 395 adult patients diagnosed with tuberculosis and human immunodeficiency virus between August 2007 and November 2009 in Kinshasa, Democratic Republic of the Congo. ART was to be initiated after 1 month of tuberculosis treatment at a CD4 count of <100 cells/mm(3) or World Health Organization stage 4 (other than extrapulmonary tuberculosis) and after 2 months of tuberculosis treatment at a CD4 count of 100-350 cells/mm(3). We used the parametric g-formula to estimate the impact of implementation fidelity on 6-month mortality. Observed implementation fidelity was low (46%); 54% of patients either experienced delays in ART initiation or did not initiate ART, which could be avoided under perfect implementation fidelity. The observed mortality risk was 12.0% (95% confidence interval (CI): 8.2, 15.7); under complete (counterfactual) implementation fidelity, the mortality risk was 7.8% (95% CI: 2.4, 12.3), corresponding to a risk reduction of 4.2% (95% CI: 0.3, 8.1) and a preventable fraction of 35.1% (95% CI: 2.9, 67.9). Strategies to achieve high implementation fidelity to CD4-stratified ART timing are needed to maximize survival benefit. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis.

PubMed

Donnell, Deborah; Baeten, Jared M; Kiarie, James; Thomas, Katherine K; Stevens, Wendy; Cohen, Craig R; McIntyre, James; Lingappa, Jairam R; Celum, Connie

2010-06-12

High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per microL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161-265) cells per microL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0.37 (95% CI 0.09-2.04) per 100 person-years in those who had initiated treatment and 2.24 (1.84-2.72) per 100 person-years in those who had not-a 92% reduction (adjusted incidence rate ratio 0.08, 95% CI 0.00-0.57, p=0.004). In participants not on ART, the highest HIV-1 transmission rate (8.79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per microL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per microL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission. Bill & Melinda Gates Foundation; US National Institutes of Health. Copyright 2010 Elsevier Ltd. All rights reserved.

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

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.

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.

Role of HIV Infection Duration and CD4 Cell Level at Initiation of Combination Anti-Retroviral Therapy on Risk of Failure

PubMed Central

Lodi, Sara; Phillips, Andrew; Fidler, Sarah; Hawkins, David; Gilson, Richard; McLean, Ken; Fisher, Martin; Post, Frank; Johnson, Anne M.; Walker-Nthenda, Louise; Dunn, David; Porter, Kholoud

2013-01-01

Background The development of HIV drug resistance and subsequent virological failure are often cited as potential disadvantages of early cART initiation. However, their long-term probability is not known, and neither is the role of duration of infection at the time of initiation. Methods Patients enrolled in the UK Register of HIV seroconverters were followed-up from cART initiation to last HIV-RNA measurement. Through survival analysis we examined predictors of virologic failure (2HIV-RNA ≥400 c/l while on cART) including CD4 count and HIV duration at initiation. We also estimated the cumulative probabilities of failure and drug resistance (from the available HIV nucleotide sequences) for early initiators (cART within 12 months of seroconversion). Results Of 1075 starting cART at a median (IQR) CD4 count 272 (190,370) cells/mm3 and HIV duration 3 (1,6) years, virological failure occurred in 163 (15%). Higher CD4 count at initiation, but not HIV infection duration at cART initiation, was independently associated with lower risk of failure (p=0.033 and 0.592 respectively). Among 230 patients initiating cART early, 97 (42%) discontinued it after a median of 7 months; cumulative probabilities of resistance and failure by 8 years were 7% (95% CI 4,11) and 19% (13,25), respectively. Conclusion Although the rate of discontinuation of early cART in our cohort was high, the long-term rate of virological failure was low. Our data do not support early cART initiation being associated with increased risk of failure and drug resistance. PMID:24086588

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.

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.

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

Estimating the Impact of Earlier ART Initiation and Increased Testing Coverage on HIV Transmission among Men Who Have Sex with Men in Mexico using a Mathematical Model.

PubMed

Caro-Vega, Yanink; del Rio, Carlos; Lima, Viviane Dias; Lopez-Cervantes, Malaquias; Crabtree-Ramirez, Brenda; Bautista-Arredondo, Sergio; Colchero, M Arantxa; Sierra-Madero, Juan

2015-01-01

To estimate the impact of late ART initiation on HIV transmission among men who have sex with men (MSM) in Mexico. An HIV transmission model was built to estimate the number of infections transmitted by HIV-infected men who have sex with men (MSM-HIV+) MSM-HIV+ in the short and long term. Sexual risk behavior data were estimated from a nationwide study of MSM. CD4+ counts at ART initiation from a representative national cohort were used to estimate time since infection. Number of MSM-HIV+ on treatment and suppressed were estimated from surveillance and government reports. Status quo scenario (SQ), and scenarios of early ART initiation and increased HIV testing were modeled. We estimated 14239 new HIV infections per year from MSM-HIV+ in Mexico. In SQ, MSM take an average 7.4 years since infection to initiate treatment with a median CD4+ count of 148 cells/mm3(25th-75th percentiles 52-266). In SQ, 68% of MSM-HIV+ are not aware of their HIV status and transmit 78% of new infections. Increasing the CD4+ count at ART initiation to 350 cells/mm3 shortened the time since infection to 2.8 years. Increasing HIV testing to cover 80% of undiagnosed MSM resulted in a reduction of 70% in new infections in 20 years. Initiating ART at 500 cells/mm3 and increasing HIV testing the reduction would be of 75% in 20 years. A substantial number of new HIV infections in Mexico are transmitted by undiagnosed and untreated MSM-HIV+. An aggressive increase in HIV testing coverage and initiating ART at a CD4 count of 500 cells/mm3 in this population would significantly benefit individuals and decrease the number of new HIV infections in Mexico.

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

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.

Immunological Response of Hiv-Infected Children to Highly Active Antiretoviral Therapy at Gondar University Hospital, North-Western Ethiopia.

PubMed

Kokeb, Mehretie; Degu, Getu

2016-01-01

The effectiveness of highly active antiretroviral therapy (HAART) in children has not been well studied specially in developing countries where the burden of HIV is high. This study was aimed to assess the immunologic response of HIV-infected children to HAART at Pediatric ART Clinic Gondar University Hospital. Institution based cross-sectional study was conducted at the Pediatric ART Clinic Gondar University Hospital from March 01-April 30, 2014. The study included 283 HIV-infected children who were on HAART for 6 months and above. Medical records of HIV-infected children were reviewed using pre-tested questionnaire. CD4 count/percent was collected every 6 months retrospectively. For all statistical significance tests, the cut-off value was p<0.05. Poison Regression was used for further analysis. The mean age of children was 6.9 years with a standard deviation of 3.4 years. The median CD4 count/percent was 232/13%, 450/21%, 540/25% and 608/27% at the time of initiation, 6, 12 and 18 months of ART, respectively. HAART initiated at higher CD4 count, good adherence and HIV status disclosure were found to have positive effects for immunological response. The study revealed that there was good Immunological response to ART, and that the maximum response was in the 1(st) 6 months of ART. Low CD4 count at initiation, undisclosed HIV status and lack of good adherence were found to cause low immunological response to HAART.

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.

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.

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.

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.

Long terms trends in CD4+ cell counts, CD8+ cell counts, and the CD4+ : CD8+ ratio

PubMed Central

Hughes, Rachael A.; May, Margaret T.; Tilling, Kate; Taylor, Ninon; Wittkop, Linda; Reiss, Peter; Gill, John; Schommers, Philipp; Costagliola, Dominique; Guest, Jodie L.; Lima, Viviane D.; d’Arminio Monforte, Antonella; Smith, Colette; Cavassini, Matthias; Saag, Michael; Castilho, Jessica L.; Sterne, Jonathan A.C.

2018-01-01

Objective: Model trajectories of CD4+ and CD8+ cell counts after starting combination antiretroviral therapy (ART) and use the model to predict trends in these counts and the CD4+ : CD8+ ratio. Design: Cohort study of antiretroviral-naïve HIV-positive adults who started ART after 1997 (ART Cohort Collaboration) with more than 6 months of follow-up data. Methods: We jointly estimated CD4+ and CD8+ cell count trends and their correlation using a bivariate random effects model, with linear splines describing their population trends, and predicted the CD4+ : CD8+ ratio trend from this model. We assessed whether CD4+ and CD8+ cell count trends and the CD4+ : CD8+ ratio trend varied according to CD4+ cell count at start of ART (baseline), and, whether these trends differed in patients with and without virological failure more than 6 months after starting ART. Results: A total of 39 979 patients were included (median follow-up was 53 months). Among patients with baseline CD4+ cell count at least 50 cells/μl, predicted mean CD8+ cell counts continued to decrease between 3 and 15 years post-ART, partly driving increases in the predicted mean CD4+ : CD8+ ratio. During 15 years of follow-up, normalization of the predicted mean CD4+ : CD8+ ratio (to >1) was only observed among patients with baseline CD4+ cell count at least 200 cells/μl. A higher baseline CD4+ cell count predicted a shorter time to normalization. Conclusion: Declines in CD8+ cell count and increases in CD4+ : CD8+ ratio occurred up to 15 years after starting ART. The likelihood of normalization of the CD4+ : CD8+ ratio is strongly related to baseline CD4+ cell count. PMID:29851663

Increased Regulatory T-Cell Percentage Contributes to Poor CD4(+) Lymphocytes Recovery: A 2-Year Prospective Study After Introduction of Antiretroviral Therapy.

PubMed

Saison, Julien; Maucort Boulch, Delphine; Chidiac, Christian; Demaret, Julie; Malcus, Christophe; Cotte, Laurent; Poitevin-Later, Francoise; Miailhes, Patrick; Venet, Fabienne; Trabaud, Mary Anne; Monneret, Guillaume; Ferry, Tristan

2015-04-01

Background.  The primary aim of this study was to determine the impact of regulatory T cells (Tregs) percentage on immune recovery in human immunodeficiency virus (HIV)-infected patients after antiretroviral therapy introduction. Methods.  A 2-year prospective study was conducted in HIV-1 chronically infected naive patients with CD4 count <500 cells/mm(3). Regulatory T cells were identified as CD4(+)CD25(high)CD127(low) cells among CD4(+) lymphocytes. Effect of Treg percentage at inclusion on CD4 evolution overtime was analyzed using a mixed-effect Poisson regression for count data. Results.  Fifty-eight patients were included (median CD4 = 293/mm(3), median Treg percentage = 6.1%). Percentage of Treg at baseline and CD4 nadir were independently related to the evolution of CD4 absolute value according to time: (1) at any given nadir CD4 count, 1% increase of initial Treg was associated with a 1.9% lower CD4 absolute value at month 24; (2) at any given Treg percentage at baseline, 10 cell/mm(3) increase of CD4 nadir was associated with a 2.4% increase of CD4 at month 24; and (3) both effects did not attenuate with time. The effect of Treg at baseline on CD4 evolution was as low as the CD4 nadir was high. Conclusions.  Regulatory T-cell percentage at baseline is a strong independent prognostic factor of immune recovery, particularly among patients with low CD4 nadir.

The immunological response of HIV-positive patients initiating HAART at the Komfo Anokye Teaching Hospital, Kumasi, Ghana.

PubMed

Annison, L; Dompreh, A; Adu-Sarkodie, Y

2013-12-01

The study sought to document the experience of immunological improvement among Ghanaian PLHIV on HAART comparing different categories of patients. Serology Unit, Komfo Anokye Teaching Hospital, Kumasi, Ghana. The study comprised a convenient sample of 303 treatment naïve HIV patients due to start HAART. Questionnaires were used to collect patient demographic and clinical data. Four CD4 counts were measured at six-monthly intervals to determine rates of CD4 change. These were pre-therapy, 1(st) post-therapy, 2(nd) post-therapy, and 3(rd) post-therapy counts. The rates of CD4 change among the different categories of patients were also compared. At baseline, women had higher CD4 count (mean of 77.4 cells/μl), and mean age of participants was 40 years. The CD4 count increased from a mean baseline of 70.2 cells/μl to 229.2, 270.0, and 297.6 cells/μl at 6, 12, and 18 months of treatment respectively (P < 0.0001 at each time point). There were no gender (P=0.46) and age (P=0.96) differences in treatment response. There was no difference (P=0.18) in treatment response comparing those with CD4 <250 cells/μl and those whose CD4 count was between 250 and 350 cells/μl at baseline although patients with baseline CD4 count <250 cells/μl showed larger increases after 12 months of treatment. Out of 282 patients with pre-therapy CD4 count ≤250 cells/μl, 241 (85.5%) and 41 (14.5%) were adherents and nonadherents respectively. Mean rate of increase was 15.2 and 8.4 cells/μl/month in adherent and non-adherent patients respectively (p=0.2). The study suggests that a sustained CD4 increase could be achieved in adherent patients commencing therapy with baseline CD4 count ≤250 cells/μl, and that these patients have greater ability for immunological recovery during 12 months of treatment The study, therefore, concludes that significant immunological improvement is possible among Ghanaian PLHIV on HAART as long as a high level of treatment adherence is observed.

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.

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.

Polymorphisms of the Kappa Opioid Receptor and Prodynorphin Genes: HIV risk and HIV Natural History

PubMed Central

Proudnikov, Dmitri; Randesi, Matthew; Levran, Orna; Yuferov, Vadim; Crystal, Howard; Ho, Ann; Ott, Jurg; Kreek, Mary Jeanne

2013-01-01

Objective Studies indicate cross-desensitization between opioid receptors (e.g., kappa opioid receptor, OPRK1), and chemokine receptors (e.g., CXCR4) involved in HIV infection. We tested whether gene variants of OPRK1 and its ligand, prodynorphin (PDYN), influence the outcome of HIV therapy. Methods Three study points, admission to the Women’s Interagency HIV Study (WIHS), initiation of highly active antiretroviral therapy (HAART) and the most recent visit were chosen for analysis as crucial events in the clinical history of the HIV patients. Regression analyses of 17 variants of OPRK1, and 11 variants of PDYN with change of viral load (VL) and CD4 count between admission and initiation of HAART, and initiation of HAART to the most recent visit to WIHS were performed in 598 HIV+ subjects including African Americans, Hispanics and Caucasians. Association with HIV status was done in 1009 subjects. Results Before HAART, greater VL decline (improvement) in carriers of PDYN IVS3+189C>T, and greater increase of CD4 count (improvement) in carriers of OPRK1 −72C>T, were found in African Americans. Also, greater increase of CD4 count in carriers of OPRK1 IVS2+7886A>G, and greater decline of CD4 count (deterioration) in carriers of OPRK1 −1205G>A, were found in Caucasians. After HAART, greater decline of VL in carriers of OPRK1 IVS2+2225G>A, and greater increase of VL in carriers of OPRK1 IVS2+10658G>T and IVS2+10963A>G, were found in Caucasians. Also, a lesser increase of CD4 count was found in Hispanic carriers of OPRK1 IVS2+2225G>A. Conclusion OPRK1 and PDYN polymorphisms may alter severity of HIV infection and response to treatment. PMID:23392455

Predictors of Clinical Progression in HIV-1-Infected Adults Initiating Combination Antiretroviral Therapy with Advanced Disease in the Asia-Pacific Region: Results from the TREAT Asia HIV Observational Database

PubMed Central

Byakwaga, H.; Petoumenos, K.; Ananworanich, J.; Zhang, F.; Boyd, M. A.; Sirisanthana, T.; Li, P. C. K.; Lee, C.; Mean, C. V.; Saphonn, V.; Omar, S. F. S.; Pujari, S.; Phanuphak, P.; Lim, P. L.; Kumarasamy, N.; Chen, Y. M. A.; Merati, T. P.; Sungkanuparph, S.; Ditangco, R.; Oka, S.; Tau, G.; Zhou, J.; Law, M. G.; Emery, S.

2013-01-01

The majority of HIV-infected patients in developing countries commences combination antiretroviral therapy (cART) with advanced disease. We examined predictors of disease progression in patients initiating cART with CD4 count ≤200 cells/mm3 in the TREAT Asia HIV Observational Database. The main outcome measure was progression to either an AIDS-defining illness or death occurring 6 months after initiation of cART. We used survival analysis methods. A total of 1255 patients contributed 2696 person years of follow-up; 73 were diagnosed with AIDS and 9 died. The rate of progression to the combined end point was 3.0 per 100 person years. The factors significantly associated with a higher risk of disease progression were Indian ethnicity, infection through intravenous drug use, lower CD4 count, and hemoglobin ≤130 g/dL at 6 months. In conclusion, measurements of CD4 count and hemoglobin at month 6 may be useful for early identification of disease progression in resource-limited settings. PMID:23422741

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.

The investigation of CD4+T-cell functions in primary HIV infection with antiretroviral therapy

PubMed Central

Sun, Yu; Fu, Yajing; Zhang, Zining; Tang, Tian; Liu, Jing; Ding, Haibo; Han, Xiaoxu; Xu, Junjie; Chu, Zhenxing; Shang, Hong; Jiang, Yongjun

2017-01-01

Abstract Human immunodeficiency virus (HIV) infection leads to reduced CD4+T-cell counts and immune dysfunction. Initiation of antiretroviral therapy (ART) in HIV primary infection has been recommended to achieve an optimal clinical outcome, but a comprehensive study on restoration of CD4+T-cell function in primary HIV-infected individuals with ART still needs to be eluciated. We investigated longitudinal changes in the CD4+T-cell counts, phenotypes, and functions in HIV-infected individuals with early ART (initiated within 6 months after HIV infection) or later ART (initiated more than 12 months after HIV infection). Patients from early ART and later ART groups had received ART for at least 1 year. Individuals with early ART had more CD4+T cells, a faster rate of CD4+T-cell recovery than those receiving later ART; the levels of CD4+T-cell activation and senescence were lower in early ART compared to those with later ART (P = .031; P = .016), but the activation was higher than normal controls (NC) (P = .001); thymic emigrant function was more upregulated in early ART than in later ART (P = .015), but still lower than NC (P = .027); proliferative capacity and interferon-γ secretion of CD4+T cells were significantly decreased in primary infection (P < .001; P = .029), and early ART restored these CD4+T-cell functions, there is no difference with NC, later ART could partially restore the functions of CD4+T cells, but it remained lower than that of NC (P = .005; P = .019). Early ART could better improve CD4+T-cell function. PMID:28700479

Could Early Antiretroviral Therapy Entail More Risks than Benefits in sub-Saharan African HIV-Infected Adults? A Model-Based Analysis

PubMed Central

Anglaret, Xavier; Scott, Callie A.; Walensky, Rochelle P.; Ouattara, Eric; Losina, Elena; Moh, Raoul; Becker, Jessica E.; Uhler, Lauren; Danel, Christine; Messou, Eugene; Eholié, Serge; Freedberg, Kenneth A.

2013-01-01

Background Initiation of antiretroviral therapy (ART) in all HIV-infected adults, regardless of count, is a proposed strategy for reducing HIV transmission. We investigated the conditions under which starting ART early could entail more risks than benefits for patients with high CD4 counts. Methods We used a simulation model to compare ART initiation upon entry to care (“immediate ART”) to initiation at CD4 ≤350 cells/μL (“WHO 2010 ART”) in African adults with CD4 counts >500 cells/μL. We varied inputs to determine the combination of parameters (population characteristics, conditions of care, treatment outcomes) that would result in higher 15-year mortality with immediate ART. Results Fifteen-year mortality was 56.7% for WHO 2010 and 51.8% for immediate ART. In one-way sensitivity analysis, lower 15-year mortality was consistently achieved with immediate ART unless the rate of fatal ART toxicity was >1.0/100PY, the rate of withdrawal from care was >1.2-fold higher or the rate of ART failure due to poor adherence was >4.3-fold higher on immediate ART. In multi-way sensitivity analysis, immediate ART led to higher mortality when moderate rates of fatal ART toxicity (0.25/100PY) were combined with rates of withdrawal from care >1.1-fold higher and rates of treatment failure >2.1-fold higher on immediate ART than on WHO 2010 ART. Conclusions In sub-Saharan Africa, ART initiation at entry into care would improve long-term survival of patients with high CD4 counts, unless it is associated with increased withdrawal from care and decreased adherence. In early ART trials, a focus on retention and adherence will be critical. PMID:22809695

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.

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

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 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.

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

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 Central

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.

2012-01-01

Background. 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. Methods. 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. Results. 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. Conclusions. 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. PMID:22955429

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

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.

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.

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+ 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.

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

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.

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.

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.

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

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.

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

Effect of Nadir CD4+ T Cell Count on Clinical Measures of Periodontal Disease in HIV+ Adults before and during Immune Reconstitution on HAART

PubMed Central

Vernon, Lance T.; Demko, Catherine A.; Babineau, Denise C.; Wang, Xuelei; Toossi, Zahra; Weinberg, Aaron; Rodriguez, Benigno

2013-01-01

Background The contribution of HIV-infection to periodontal disease (PD) is poorly understood.  We proposed that immunological markers would be associated with improved clinical measures of PD. Methods We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥1 site with periodontal probing depth (PPD) ≥5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥4.0mm, and bleeding on probing (BOP) at ≥4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD. Results Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD. Conclusion Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults. PMID:24146949

[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.

Cost-Effectiveness of Initiating Antiretroviral Therapy at Different Points in TB Treatment in HIV-TB Coinfected Ambulatory Patients in South Africa.

PubMed

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Abdool Karim, Salim

2015-08-15

Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV coinfected patients. In patients with CD4 counts <50 cells per cubic millimeter, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost-effectiveness of starting ART at various time points during TB treatment in patients with CD4 counts ≥50 cells per cubic millimeter. In the SAPiT trial, 642 HIV-TB coinfected patients were randomized to 3 arms: receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct health care costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. For patients with CD4 count ≥50 cells per cubic millimeter, median monthly variable costs per patient were US $116, US $113, and US $102 in Arm-1, Arm-2 and Arm-3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2, and 19 deaths in 172 patients in Arm-3. Although the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was US $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Initiation of ART after the completion of the intensive phase of TB treatment is cost-effective for patients with CD4 counts ≥50 cells per cubic millimeter.

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.

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.

Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

PubMed

Yanik, Elizabeth L; Napravnik, Sonia; Cole, Stephen R; Achenbach, Chad J; Gopal, Satish; Olshan, Andrew; Dittmer, Dirk P; Kitahata, Mari M; Mugavero, Michael J; Saag, Michael; Moore, Richard D; Mayer, Kenneth; Mathews, W Christopher; Hunt, Peter W; Rodriguez, Benigno; Eron, Joseph J

2013-09-01

Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of 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

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.

Costs of HIV/AIDS treatment in Indonesia by time of treatment and stage of disease.

PubMed

Siregar, Adiatma Y M; Tromp, Noor; Komarudin, Dindin; Wisaksana, Rudi; van Crevel, Reinout; van der Ven, Andre; Baltussen, Rob

2015-09-30

We report an economic analysis of Human Immunodeficiency Virus (HIV) care and treatment in Indonesia to assess the options and limitations of costs reduction, improving access, and scaling up services. We calculated the cost of providing HIV care and treatment in a main referral hospital in West Java, Indonesia from 2008 to 2010, differentiated by initiation of treatment at different CD4 cell count levels (0-50, 50-100, 100-150, 150-200, and >200 cells/mm(3)); time of treatment; HIV care and opportunistic infections cost components; and the costs of patients for seeking and undergoing care. Before antiretroviral treatment (ART) initiation, costs were dominated by laboratory tests (>65 %), and after initiation, by antiretroviral drugs (≥60 %). Average treatment costs per patient decreased with time on treatment (e.g. from US$580 per patient in the first 6 month to US$473 per patient in months 19-24 for those with CD4 cell counts under 50 cells/mm(3)). Higher CD4 cell counts at initiation resulted in lower laboratory and opportunistic infection treatment costs. Transportation cost dominated the costs of patients for seeking and undergoing care (>40 %). Costs of providing ART are highest during the early phase of treatment. Costs reductions can potentially be realized by early treatment initiation and applying alternative laboratory tests with caution. Scaling up ART at the community level in certain high prevalence settings may improve early uptake, adherence, and reduce transportation costs.

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.

Changing mortality risk associated with CD4 cell response to antiretroviral therapy in South Africa

PubMed Central

Lawn, Stephen D.; Little, Francesca; Bekker, Linda-Gail; Kaplan, Richard; Campbel, Elizabeth; Orrell, Catherine; Wood, Robin

2013-01-01

Objective To determine the relationship between mortality risk and the CD4 cell response to antiretroviral therapy (ART). Design Observational community-based ART cohort in South Africa. Methods CD4 cell counts were measured 4 monthly, and deaths were prospectively ascertained. Cumulative person-time accrued within a range of updated CD4 cell count strata (CD4 cell-strata) was calculated and used to derive CD4 cell-stratified mortality rates. Results Patients (2423) (median baseline CD4 cell count of 105 cells/ml) were observed for up to 5 years of ART. One hundred and ninety-seven patients died during 3155 person years of observation. In multivariate analysis, mortality rate ratios associated with 0–49, 50–99, 100–199, 200–299, 300– 399, 400–499 and at least 500 cells/ml updated CD4 cell-strata were 11.6, 4.9, 2.6, 1.7, 1.5, 1.4 and 1.0, respectively. Analysis of CD4 cell count recovery permitted calculations of person-time accrued within these CD4 cell strata. Despite rapid immune recovery, high mortality in the first year of ART was related to the large proportion of person-time accrued within CD4 cell-strata less than 200 cells/ml. Moreover, patients with baseline CD4 cell counts less than 100 cells/ml had much higher cumulative mortality estimates at 1 and 4 years (11.6 and 16.7%) compared with those of patients with baseline counts of at least 100 cells/ml (5.2 and 9.5%) largely because of greater cumulative person-time at CD4 cell counts less than 200 cells/ml. Conclusion: Updated CD4 cell counts are the variable most strongly associated with mortality risk during ART. High cumulative mortality risk is associated with person-time accrued at low CD4 cell counts. National HIV programmes in resource-limited settings should be designed to minimize the time patients spend with CD4 cell counts less than 200 cells/ml both before and during ART. PMID:19114870

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 patterns in CD4 response are determined by an interaction between baseline CD4 cell count, viral load, and time: The Asia Pacific HIV Observational Database (APHOD).

PubMed

Egger, Sam; Petoumenos, Kathy; Kamarulzaman, Adeeba; Hoy, Jennifer; Sungkanuparph, Somnuek; Chuah, John; Falster, Kathleen; Zhou, Jialun; Law, Matthew G

2009-04-15

Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time and, in particular, the role of baseline and follow-up covariates. Patients in Asia Pacific HIV Observational Database who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least 1 follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period after the commencement of cART for up to 6 years. A total of 1638 patients fulfilled the inclusion criteria with a median follow-up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (P < 0.001), pre-cART hepatitis C coinfection (P = 0.038), prior AIDS (P = 0.019), baseline viral load < or equal to 100,000 copies per milliliter (P < 0.001), and the Asia Pacific region compared with Australia (P = 0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count, and post-cART viral burden (P < 0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load, CD4 cell counts seemed to converge for all baseline CD4 levels. Our analysis suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response, and time.

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.

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.

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

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.

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.

Barriers to Universal Prescribing of Antiretroviral Therapy by HIV Care Providers in the United States, 2013–2014

PubMed Central

Weiser, John; Brooks, John T.; Skarbinski, Jacek; West, Brady T.; Duke, Christopher C.; Gremel, Garrett W.; Beer, Linda

2017-01-01

Introduction HIV treatment guidelines recommend initiating antiretroviral therapy (ART) regardless of CD4 cell (CD4) count, barring contraindications or barriers to treatment. An estimated 6% of persons receiving HIV care in 2013 were not prescribed ART. We examined reasons for this gap in the care continuum. Methods During 2013–2014, we surveyed a probability sample of HIV care providers, of whom 1234 returned surveys (64.0% adjusted response rate). We estimated percentages of providers who followed guidelines and their characteristics, and who deferred ART prescribing for any reason. Results Barring contraindications, 71.2% of providers initiated ART regardless of CD4 count. Providers less likely to initiate had caseloads ≤20 vs. >200 patients [adjusted prevalence ratios (aPR) 0.69, 95% confidence interval (CI): 0.47 to 1.02, P = 0.03], practiced at non–Ryan White HIV/AIDS Program-funded facilities (aPR 0.85, 95% CI: 0.74 to 0.98, P = 0.02), or reported pharmaceutical assistance programs provided insufficient medication to meet patients’ needs (aPR 0.79, 95% CI: 0.65 to 0.98, P = 0.02). In all, 17.0% never deferred prescribing ART, 69.6% deferred for 1%–10% of patients, and 13.3% deferred for >10%. Among providers who had deferred ART, 59.4% cited patient refusal as a reason in >50% of cases, 31.1% reported adherence concerns because of mental health disorders or substance abuse, and 21.4% reported adherence concerns because of social problems, eg, homelessness, as factors in >50% of cases when deferring ART. Conclusions An estimated 29% of HIV care providers had not adopted recommendations to initiate ART regardless of CD4 count, barring contraindications, or barriers to treatment. Low-volume providers and those at non–Ryan White HIV/AIDS Program-funded facilities were less likely to follow this guideline. Among all providers, leading reasons for deferring ART included patient refusal and adherence concerns. PMID:28002186

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.

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

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.

Initiation of antiretroviral therapy in patients with a CD4 count of less than 350 cells: a retrospective audit against key indicators from the CQUIN payment framework.

PubMed

Mercer, R M; Olarinde, O; Ryan, C; Greig, J; Yeeles, H; Walker, A; Walker, H; Meardon, N C

2011-12-01

A proportion of funding for the South Yorkshire HIV Network is dependant on meeting the targets of the Commissioning for Quality and Innovation (CQUIN) payment framework. This states that 85% of patients with a CD4 count below 350 should be on antiretroviral therapy (ART). We also audited how many patients we started on treatment within six weeks. We found 88% of the 243 patients were on ART at the end of the audit, but significantly less had been started on treatment within six weeks of their CD4 count falling below 350. Although the target was achieved, there were patients who should be excluded as shown by other clinical guidelines, for example patients on treatment for tuberculosis. If these patients were excluded and the threshold level increased, it would help emphasize the at-risk patient group and lead to a fairer allocation of funding.

Predicting CD4 count changes among patients on antiretroviral treatment: Application of data mining techniques.

PubMed

Kebede, Mihiretu; Zegeye, Desalegn Tigabu; Zeleke, Berihun Megabiaw

2017-12-01

To monitor the progress of therapy and disease progression, periodic CD4 counts are required throughout the course of HIV/AIDS care and support. The demand for CD4 count measurement is increasing as ART programs expand over the last decade. This study aimed to predict CD4 count changes and to identify the predictors of CD4 count changes among patients on ART. A cross-sectional study was conducted at the University of Gondar Hospital from 3,104 adult patients on ART with CD4 counts measured at least twice (baseline and most recent). Data were retrieved from the HIV care clinic electronic database and patients` charts. Descriptive data were analyzed by SPSS version 20. Cross-Industry Standard Process for Data Mining (CRISP-DM) methodology was followed to undertake the study. WEKA version 3.8 was used to conduct a predictive data mining. Before building the predictive data mining models, information gain values and correlation-based Feature Selection methods were used for attribute selection. Variables were ranked according to their relevance based on their information gain values. J48, Neural Network, and Random Forest algorithms were experimented to assess model accuracies. The median duration of ART was 191.5 weeks. The mean CD4 count change was 243 (SD 191.14) cells per microliter. Overall, 2427 (78.2%) patients had their CD4 counts increased by at least 100 cells per microliter, while 4% had a decline from the baseline CD4 value. Baseline variables including age, educational status, CD8 count, ART regimen, and hemoglobin levels predicted CD4 count changes with predictive accuracies of J48, Neural Network, and Random Forest being 87.1%, 83.5%, and 99.8%, respectively. Random Forest algorithm had a superior performance accuracy level than both J48 and Artificial Neural Network. The precision, sensitivity and recall values of Random Forest were also more than 99%. Nearly accurate prediction results were obtained using Random Forest algorithm. This algorithm could be used in a low-resource setting to build a web-based prediction model for CD4 count changes. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Current CD4 cell count and the short-term risk of AIDS and death before the availability of effective antiretroviral therapy in HIV-infected children and adults.

PubMed

Dunn, David; Woodburn, Patrick; Duong, Trinh; Peto, Julian; Phillips, Andrew; Gibb, Di; Porter, Kholoud

2008-02-01

Currently, there are no comparable estimates of the short-term risk of disease progression in the absence of effective antiretroviral therapy for human immunodeficiency virus (HIV)-infected adults and children. A joint analysis of 2 large studies of children with vertically acquired HIV infection (the HIV Paediatric Prognostic Markers Collaborative Study) and adults with seroconversion (the CASCADE [Concerted Action on Sero-Conversion to AIDS and Death in Europe] collaboration) was conducted. Follow-up was censored at the end of 1995, before the introduction of combination antiretroviral therapy. The incidence rates of death and AIDS or death (AIDS/death) were estimated on the basis of age and current CD4 cell count. A total of 1260 deaths (over 20,500 person-years of follow-up) and 1894 initial AIDS events (over 17,200 person-years of follow-up) were observed among 6741 patients (3244 children [i.e., patients < or =15 years of age] and 3497 adults). Young children (age, <5 years) experienced high morbidity and mortality rates. After adjustment for the CD4 cell count, the effect of age on disease progression was not significant among older children, whereas the risk increased markedly in association with increasing age among adults. Death rates were similar among older children and adults aged approximately 20 years, as were the rates of progression to AIDS/death when cases of serious recurrent bacterial infection, which has a more restrictive case definition in adults, were excluded. Similar CD4 cell count criteria for initiation of antiretroviral therapy can be applied to adults and children > or = 5 years of age.

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.

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.

A Brief Chronicle of CD4 as a Biomarker for HIV/AIDS: A Tribute to the Memory of John L. Fahey.

PubMed

Kagan, Jonathan M; Sanchez, Ana M; Landay, Alan; Denny, Thomas N

Foundational cellular immunology research of the 1960s and 1970s, together with the advent of monoclonal antibodies and flow cytometry, provided the knowledge base and the technological capability that enabled the elucidation of the role of CD4 T cells in HIV infection. Research identifying the sources and magnitude of variation in CD4 measurements, standardized reagents and protocols, and the development of clinical flow cytometers all contributed to the feasibility of widespread CD4 testing. Cohort studies and clinical trials provided the context for establishing the utility of CD4 for prognosis in HIV-infected persons, initial assessment of in vivo antiretroviral drug activity, and as a surrogate marker for clinical outcome in antiretroviral therapeutic trials. Even with sensitive HIV viral load measurement, CD4 cell counting is still utilized in determining antiretroviral therapy eligibility and time to initiate therapy. New point of care technologies are helping both to lower the cost of CD4 testing and enable its use in HIV test and treat programs around the world.

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

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

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.

Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV.

PubMed

Mellberg, Tomas; Gonzalez, Veronica D; Lindkvist, Annica; Edén, Arvid; Sönnerborg, Anders; Sandberg, Johan K; Svennerholm, Bo; Gisslén, Magnus

2011-06-28

High dosage of intravenous immunoglobulin (IVIG) has been observed as a possible activator of HIV gene expression in latently infected resting CD4+ T-cells, leading to a substantial decrease in both the reservoir and the residual plasma viremia when added to effective ART. IVIG treatment has also been reported to expand T regulatory cells (Tregs). The aim of this study was to evaluate possible long-term effect of IVIG treatment on residual viremia and T-lymphocyte activation. Nine HIV-infected subjects on effective ART included in a previously reported study on IVIG treatment were evaluated 48-104 weeks after therapy. In addition, 14 HIV-infected controls on suppressive ART were included. HIV-1 RNA was analyzed in cell-free plasma by using an ultrasensitive PCR-method with a detection limit of 2 copies/mL. T-lymphocyte activation markers and serum interleukins were measured. Plasma residual viremia rebounded to pre-treatment levels, 48-104 weeks after the initial decrease that was observed following treatment with high-dosage IVIG. No long-term effect was observed regarding T-lymphocyte activation markers, T-regulatory cells or serum interleukins. In a post-hoc analysis, a correlation between plasma HIV-1-RNA and CD4+ T-cell count was found in both IVIG-treated patients and controls. These results indicate that the decrease in the latent HIV-1 pool observed during IVIG treatment is transient. Although not our primary objective, we found a correlation between HIV-1 RNA and CD4+ T-cell count suggesting the possibility that patients with a higher CD4+ T-cell count might harbor a larger residual pool of latently infected CD4+ T-cells.

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.

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.

Cytomegalovirus retinitis and HIV: Case reviews from KwaZulu-Natal Province, South Africa.

PubMed

Hassan-Moosa, R; Chinappa, T; Jeena, L; Visser, L; Naidoo, K

2017-09-22

Retinal cytomegalovirus (CMV) infection is a common opportunistic infection and remains a significant contributor to visual loss in patients with AIDS. We highlight the poor outcomes of CMV retinitis in three HIV-infected patients who were initiated on antiretroviral therapy (ART). We conducted a retrospective chart review of advanced stage HIV-infected patients with known CMV retinitis.Case 1. A 37-year-old man, with a CD4+ cell count of 35 cells/µL, presented for ART initiation with a 5-month history of visual loss in his left eye. Fundoscopy showed left eye CMV retinitis and right eye HIV retinopathy. ART and 5 months of weekly intravitreal ganciclovir injections (left eye) were commenced. Six-month outcomes included virological suppression, and visual acuity in the right eye of 6/6 and in the left eye of 3/60.Case 2. A 31-year-old woman, with a CD4+ cell count of 39 cells/µL and on tuberculosis therapy, presented for ART initiation. She presented with a 2-month history of decreased visual acuity. Fundoscopy showed bilateral CMV retinitis, which was more pronounced in the left eye. ART and 8 months of intravitreal ganciclovir injections were commenced. Six-month outcomes included virological suppression and visual acuity in the right eye of 6/9, and in the left eye of 6/24.Case 3. A 29-year-old woman, with a CD4+ cell count of 24 cells/µL, who was on tuberculosis therapy and ART, complained of blurred vision at her 2-month ART follow-up visit. Fundoscopy showed bilateral retinal detachment secondary to CMV retinitis. While silicone oil tamponade and subsequent retinectomy successfully repaired the right eye, extensive damage rendered the left eye irreparable. Six-month outcomes included virological suppression, with 6/120 visual acuity in the right eye and complete blindness in the left eye. CMV retinitis causes debilitating, permanent sequelae, which is preventable by ART initiation at higher CD4+ cell counts. Despite achieving virological suppression, vision could not be completely restored in these patients, irrespective of the severity of CMV retinitis.

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.

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.

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.

High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya

PubMed Central

Kwarisiima, Dalsone; Kamya, Moses R.; Owaraganise, Asiphas; Mwangwa, Florence; Byonanebye, Dathan M.; Ayieko, James; Plenty, Albert; Black, Doug; Clark, Tamara D.; Nzarubara, Bridget; Snyman, Katherine; Brown, Lillian; Bukusi, Elizabeth; Cohen, Craig R.; Geng, Elvin H.; Charlebois, Edwin D.; Ruel, Theodore D.; Petersen, Maya L.; Havlir, Diane; Jain, Vivek

2017-01-01

Abstract Introduction: The 2015 WHO recommendation of antiretroviral therapy (ART) for all HIV-positive persons calls for treatment initiation in millions of persons newly eligible with high CD4+ counts. Efficient and effective care models are urgently needed for this population. We evaluated clinical outcomes of asymptomatic HIV-positive adults and children starting ART with high CD4+ counts using a novel streamlined care model in rural Uganda and Kenya. Methods: In the 16 intervention communities of the HIV test-and-treat Sustainable East Africa Research for Community Health Study (NCT01864603), all HIV-positive individuals irrespective of CD4 were offered ART (efavirenz [EFV]/tenofovir disoproxil fumarate + emtricitabine (FTC) or lamivudine (3TC). We studied adults (≥fifteen years) with CD4 ≥ 350/μL and children (two to fourteen years) with CD4 > 500/μL otherwise ineligible for ART by country guidelines. Clinics implemented a patient-centred streamlined care model designed to reduce patient-level barriers and maximize health system efficiency. It included (1) nurse-conducted visits with physician referral of complex cases, (2) multi-disease chronic care (including for hypertension/diabetes), (3) patient-centred, friendly staff, (4) viral load (VL) testing and counselling, (5) three-month return visits and ART refills, (6) appointment reminders, (7) tiered tracking for missed appointments, (8) flexible clinic hours (outside routine schedule) and (9) telephone access to clinicians. Primary outcomes were 48-week retention in care, viral suppression (% with measured week 48 VL ≤ 500 copies/mL) and adverse events. Results: Overall, 972 HIV-positive adults with CD4+ ≥ 350/μL initiated ART with streamlined care. Patients were 66% female and had median age thirty-four years (IQR, 28–42), CD4+ 608/μL (IQR, 487–788/μL) and VL 6775 copies/mL (IQR, <500–37,003 c/mL). At week 48, retention was 92% (897/972; 2 died/40 moved/8 withdrew/4 transferred care/21/964 [2%] were lost to follow-up). Viral suppression occurred in 778/838 (93%) and 800/972 (82%) in intention-to-treat analysis. Grade III/IV clinical/laboratory adverse events were rare: 95 occurred in 74/972 patients (7.6%). Only 8/972 adults (0.8%) switched ART from EFV to lopinavir (LPV) (n = 2 for dizziness, n = 2 for gynaecomastia, n = 4 for other reasons). Among 83 children, week 48 retention was 89% (74/83), viral suppression was 92% (65/71) and grade III/IV adverse events occurred in 4/83 (4.8%). Conclusions: Using a streamlined care model, viral suppression, retention and ART safety were high among asymptomatic East African adults and children with high CD4+ counts initiating treatment. Clinical Trial Number: NCT01864603 PMID:28770596

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.

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.

Temporal trends of time to antiretroviral treatment initiation, interruption and modification: examination of patients diagnosed with advanced HIV in Australia.

PubMed

Wright, Stephen T; Law, Matthew G; Cooper, David A; Keen, Phillip; McDonald, Ann; Middleton, Melanie; Woolley, Ian; Kelly, Mark; Petoumenos, Kathy

2015-01-01

HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods.

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.

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.

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

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.

Immunovirological response to triple nucleotide reverse-transcriptase inhibitors and ritonavir-boosted protease inhibitors in treatment-naive HIV-2-infected patients: The ACHIEV2E Collaboration Study Group.

PubMed

Benard, Antoine; van Sighem, Ard; Taieb, Audrey; Valadas, Emilia; Ruelle, Jean; Soriano, Vicente; Calmy, Alexandra; Balotta, Claudia; Damond, Florence; Brun-Vezinet, Françoise; Chene, Geneviève; Matheron, Sophie

2011-05-01

Triple nucleoside reverse-transcriptase inhibitors (NRTIs) are recommended by the World Health Organization as first-line regimen in treatment-naïve HIV-2-infected patients. However, ritonavir-boosted protease inhibitor (PI/r)-containing regimens are frequently prescribed. In the absence of previous randomized trials, we retrospectively compared these regimens in observational cohorts. HIV-2-infected patients from 7 European cohorts who started triple NRTI or PI/r since January 1998 were included. Piecewise linear models were used to estimate CD4 cell count and plasma HIV-2 RNA level slopes, differentiating an early phase (until end of month 3) and a second phase (months 4-12). On-treatment analyses censored data at major treatment modification and systematically at month 12. Forty-four patients started triple NRTI therapy and 126 started PI/r therapy. Overall, the median CD4 cell count was 191 cells/mm(3) and the median plasma HIV-2 RNA level was ≥2.7 log(10) copies/ml in 61% of the patients at combination antiretroviral therapy (cART) initiation; the median duration of the first cART was 20 months, not differing between groups. PI/r regimens were associated with better CD4 cell count and HIV-2 RNA level outcomes, compared with NRTI regimens. Estimated CD4 cell count slopes were +6 and +12 cells/mm(3)/month during the early phase (P = .22), and -60 cells/mm(3)/year versus +76 cells/mm(3)/year during the second phase (P = .002), for triple NRTI and PI/r, respectively. Estimated mean HIV-2 RNA levels at month 12 in patients with detectable viremia at cART initiation were 4.0 and 2.2 log(10) copies/ml, respectively (P = .005). In this observational study, PI/r-containing regimens showed superior efficacy over triple NRTI regimens as first-line therapy in HIV-2-infected patients.

Country of infection among HIV-infected patients born abroad living in French Guiana.

PubMed

Nacher, Mathieu; Adriouch, Leila; Van Melle, Astrid; Parriault, Marie-Claire; Adenis, Antoine; Couppié, Pierre

2018-01-01

Over 75% of patients in the HIV cohort in French Guiana are of foreign origin. Our objective was to estimate what proportion of the migrant population of HIV-infected patients in Cayenne had been infected in French Guiana. We included patients of known foreign origin who were followed in Cayenne, for whom the year of arrival in French Guiana was known and the initial CD4 count at the time of diagnosis was available. The time between seroconversion and time at diagnosis was estimated using the formula [square root (CD4 at seroconversion)-square root(CD4 at HIV diagnosis)] / slope of CD4 decline.CD4 counts at the time of infection and the slope were computed in an age and ethnicity-dependent variable. The median estimated time between infection and diagnosis was 4.5 years (IQR = 0.2-9.2). Overall, using a median estimate of CD4 count at the time of infection, it was estimated that 53.2% (95% CI = 48.3-58%) of HIV infected foreign patients had acquired HIV after having arrived in French Guiana. Patients having arrived in French Guiana before and during the 1990s and those receiving their HIV diagnosis before 2010 were more likely to have been infected in French Guiana. Contrary to widespread belief suggesting that most migrants are already HIV-infected when they arrive in French Guiana, a large proportion of foreign HIV patients seem acquire the virus in French Guiana.There is still much to do in terms of primary prevention and testing among migrants.

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.

Effects of CD4 monitoring frequency on clinical endpoints in clinically stable HIV-infected patients with viral suppression

PubMed Central

Ahn, Jin Young; Boettiger, David; Law, Matthew; Kumarasamy, Nagalingeswaran; Yunihastuti, Evy; Chaiwarith, Romanee; Lee, Man Po; Sim, Benedict LH; Oka, Shinichi; Wong, Wingwai; Kamarulzaman, Adeeba; Kantipong, Pacharee; Phanuphak, Praphan; Ng, Oon Tek; Kiertiburanakul, Sasisopin; Zhang, Fujie; Pujari, Sanjay; Ditangco, Rossana; Ratanasuwan, Winai; Merati, Tuti Parwati; Saphonn, Vonthanak; Sohn, Annette H.; Choi, Jun Yong

2015-01-01

Background Current treatment guidelines for HIV infection recommend routine CD4+ lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression. Methods In a regional HIV observational cohort in the Asia-Pacific, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells/μL who had CD4 testing 6 monthly were analyzed. Main study endpoints were occurrence of one CD4 count <200 cells/μL (single CD4<200) and two CD4 counts <200 cells/μL within a 6-month period (confirmed CD4<200). A comparison of time to single and confirmed CD4<200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprised of the same patients with annual CD4 testing by removing every second CD4 count. Results Among 1538 patients, the rate of single CD4<200 was 3.45/100 patient-years, and of confirmed CD4<200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells/μL were significantly more likely to experience confirmed CD4<200 compared with patients with higher baseline CD4 (hazard ratio 55.47 [95% confidence interval 7.36–418.20], p<0.001 versus baseline CD4 ≥500 cells/μL). Cumulative probabilities of confirmed CD4<200 was also higher in patients with baseline CD4 200-249 cells/μL compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4<200 between biannual and annual CD4 measurement (p=0.336). Conclusions Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells/μL may be sufficient for clinical management. PMID:25850606

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.

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.

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

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.

Linear Mode HgCdTe Avalanche Photodiodes for Photon Counting Applications

NASA Technical Reports Server (NTRS)

Sullivan, William, III; Beck, Jeffrey; Scritchfield, Richard; Skokan, Mark; Mitra, Pradip; Sun, Xiaoli; Abshire, James; Carpenter, Darren; Lane, Barry

2015-01-01

An overview of recent improvements in the understanding and maturity of linear mode photon counting with HgCdTe electron-initiated avalanche photodiodes is presented. The first HgCdTe LMPC 2x8 format array fabricated in 2011 with 64 micron pitch was a remarkable success in terms of demonstrating a high single photon signal to noise ratio of 13.7 with an excess noise factor of 1.3-1.4, a 7 ns minimum time between events, and a broad spectral response extending from 0.4 micron to 4.2 micron. The main limitations were a greater than 10x higher false event rate than expected of greater than 1 MHz, a 5-7x lower than expected APD gain, and a photon detection efficiency of only 50% when greater than 60% was expected. This paper discusses the reasons behind these limitations and the implementation of their mitigations with new results.

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

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa.

PubMed

Larson, Bruce A; Rockers, Peter C; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K; Cassim, Naseem; Coetzee, Lindi M; Greene, Gregory S; Chiller, Tom M; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P

2016-01-01

In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved.

Screening HIV-Infected Patients with Low CD4 Counts for Cryptococcal Antigenemia prior to Initiation of Antiretroviral Therapy: Cost Effectiveness of Alternative Screening Strategies in South Africa

PubMed Central

Rockers, Peter C.; Bonawitz, Rachael; Sriruttan, Charlotte; Glencross, Deborah K.; Cassim, Naseem; Coetzee, Lindi M.; Greene, Gregory S.; Chiller, Tom M.; Vallabhaneni, Snigdha; Long, Lawrence; van Rensburg, Craig; Govender, Nelesh P.

2016-01-01

Background In 2015 South Africa established a national cryptococcal antigenemia (CrAg) screening policy targeted at HIV-infected patients with CD4+ T-lymphocyte (CD4) counts <100 cells/ μl who are not yet on antiretroviral treatment (ART). Two screening strategies are included in national guidelines: reflex screening, where a CrAg test is performed on remnant blood samples from CD4 testing; and provider-initiated screening, where providers order a CrAg test after a patient returns for CD4 test results. The objective of this study was to compare costs and effectiveness of these two screening strategies. Methods We developed a decision analytic model to compare reflex and provider-initiated screening in terms of programmatic and health outcomes (number screened, number identified for preemptive treatment, lives saved, and discounted years of life saved) and screening and treatment costs (2015 USD). We estimated a base case with prevalence and other parameters based on data collected during CrAg screening pilot projects integrated into routine HIV care in Gauteng, Free State, and Western Cape Provinces. We conducted sensitivity analyses to explore how results change with underlying parameter assumptions. Results In the base case, for each 100,000 CD4 tests, the reflex strategy compared to the provider-initiated strategy has higher screening costs ($37,536 higher) but lower treatment costs ($55,165 lower), so overall costs of screening and treatment are $17,629 less with the reflex strategy. The reflex strategy saves more lives (30 lives, 647 additional years of life saved). Sensitivity analyses suggest that reflex screening dominates provider-initiated screening (lower total costs and more lives saved) or saves additional lives for small additional costs (< $125 per life year) across a wide range of conditions (CrAg prevalence, patient and provider behavior, patient survival without treatment, and effectiveness of preemptive fluconazole treatment). Conclusions In countries with substantial numbers of people with untreated, advanced HIV disease such as South Africa, CrAg screening before initiation of ART has the potential to reduce cryptococcal meningitis and save lives. Reflex screening compared to provider-initiated screening saves more lives and is likely to be cost saving or have low additional costs per additional year of life saved. PMID:27390864

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

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.

Immune recovery in HIV-infected patients after Candida esophagitis is impaired despite long-term antiretroviral therapy

PubMed Central

Stuehler, Claudia; Bernardini, Claudia; Elzi, Luigia; Stoeckle, Marcel; Zimmerli, Stefan; Furrer, Hansjakob; Günthard, Huldrych F.; Leibundgut-Landmann, Salomé; Battegay, Manuel; Khanna, Nina

2016-01-01

Objective: Candida esophagitis belongs to the most common AIDS-defining diseases; however, a comprehensive immune pathogenic concept is lacking. Design: We investigated the immune status of 37 HIV-1-infected patients from the Swiss HIV cohort study at diagnosis of Candida esophagitis, 1 year before, 1 year later and after 2 years of suppressed HIV RNA. We compared these patients with three groups: 37 HIV-1-infected patients without Candida esophagitis but similar CD4+ cell counts as the patients at diagnosis (advanced HIV group), 15 HIV-1-infected patients with CD4+ cell counts higher than 500 cells/μl, CD4+ cell nadirs higher than 350 cells/μl and suppressed HIV RNA under combination antiretroviral therapy (cART) (early cART group) and 20 healthy individuals. Methods: We investigated phenotype, cytokine production and proliferative capacity of different immune cells by flow cytometry and enzyme-linked immunosorbent spot. Results: We found that patients with Candida esophagitis had nearly abolished CD4+ cell proliferation in response to Candida albicans, significantly increased percentages of dysfunctional CD4+ cells, significantly decreased cytotoxic natural killer cell counts and peripheral innate lymphoid cell counts and significantly reduced IFN-γ and IL-17 production compared with the early cART group and healthy individuals. Most of these defects remained for more than 2 years despite viral suppression. The advanced HIV group without opportunistic infection showed partly improved immune recovery. Conclusion: Our data indicate that Candida esophagitis in HIV-1-infected patients is caused by an accumulation of multiple, partly Candida-specific immunological defects. Long-term immune recovery is impaired, illustrating that specific immunological gaps persist despite cART. These data also support the rationale for early cART initiation to prevent irreversible immune defects. PMID:27149086

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.

Impact of HLA Selection Pressure on HIV Fitness at a Population Level in Mexico and Barbados

PubMed Central

Payne, Rebecca; Soto-Nava, Maribel; Avila-Rios, Santiago; Valenzuela-Ponce, Humberto; Adland, Emily; Leitman, Ellen; Brener, Jacqui; Muenchhoff, Maximilian; Branch, Songee; Landis, Clive; Reyes-Teran, Gustavo; Goulder, Philip

2014-01-01

ABSTRACT Previous studies have demonstrated that effective cytotoxic T lymphocyte (CTL) responses drive the selection of escape mutations that reduce viral replication capacity (VRC). Escape mutations, including those with reduced VRC, can be transmitted and accumulate in a population. Here we compared two antiretroviral therapy (ART)-naive HIV clade B-infected cohorts, in Mexico and Barbados, in which the most protective HLA alleles (HLA-B*27/57/58:01/81:01) are differentially expressed, at 8% and 34%, respectively. Viral loads were significantly higher in Mexico than in Barbados (median, 40,774 versus 14,200; P < 0.0001), and absolute CD4+ T-cell counts were somewhat lower (median, 380/mm3 versus 403/mm3; P = 0.007). We tested the hypothesis that the disparate frequencies of these protective HLA alleles would be associated with a higher VRC at the population level in Mexico. Analysis of VRC in subjects in each cohort, matched for CD4+ T-cell count, revealed that the VRC was indeed higher in the Mexican cohort (mean, 1.13 versus 1.03; P = 0.0025). Although CD4 counts were matched, viral loads remained significantly higher in the Mexican subjects (P = 0.04). This VRC difference was reflected by a significantly higher frequency in the Barbados cohort of HLA-B*27/57/58:01/81:01-associated Gag escape mutations previously shown to incur a fitness cost on the virus (P = 0.004), a difference between the two cohorts that remained statistically significant even in subjects not expressing these protective alleles (P = 0.01). These data suggest that viral set points and disease progression rates at the population level may be significantly influenced by the prevalence of protective HLA alleles such as HLA-B*27/57/58:01/81:01 and that CD4 count-based guidelines to initiate antiretroviral therapy may need to be modified accordingly, to optimize the effectiveness of treatment-for-prevention strategies and reduce HIV transmission rates to the absolute minimum. IMPORTANCE Immune control of HIV at an individual level is strongly influenced by the HLA class I genotype. HLA class I molecules mediating effective immune control, such as HLA-B*27 and HLA-B*57, are associated with the selection of escape mutants that reduce viral replicative capacity. The escape mutants selected in infected patients can be transmitted and affect the viral load and CD4 count in the recipient. These findings prompt the hypothesis that the frequency of protective alleles in a population may affect viral set points and rates of disease progression in that population. These studies in Mexico and Barbados, where the prevalence rates of protective HLA alleles are 8% and 34%, respectively, support this hypothesis. These data suggest that antiretroviral therapy (ART) treatment-for-prevention strategies will be less successful in populations such as those in Mexico, where viral loads are higher for a given CD4 count. Consideration may therefore usefully be given to ART initiation at higher absolute CD4 counts in such populations to optimize the impact of ART for prevention. PMID:25008926

Impact of HLA selection pressure on HIV fitness at a population level in Mexico and Barbados.

PubMed

Juarez-Molina, Claudia I; Payne, Rebecca; Soto-Nava, Maribel; Avila-Rios, Santiago; Valenzuela-Ponce, Humberto; Adland, Emily; Leitman, Ellen; Brener, Jacqui; Muenchhoff, Maximilian; Branch, Songee; Landis, Clive; Reyes-Teran, Gustavo; Goulder, Philip

2014-09-01

Previous studies have demonstrated that effective cytotoxic T lymphocyte (CTL) responses drive the selection of escape mutations that reduce viral replication capacity (VRC). Escape mutations, including those with reduced VRC, can be transmitted and accumulate in a population. Here we compared two antiretroviral therapy (ART)-naive HIV clade B-infected cohorts, in Mexico and Barbados, in which the most protective HLA alleles (HLA-B*27/57/58:01/81:01) are differentially expressed, at 8% and 34%, respectively. Viral loads were significantly higher in Mexico than in Barbados (median, 40,774 versus 14,200; P < 0.0001), and absolute CD4(+) T-cell counts were somewhat lower (median, 380/mm(3) versus 403/mm(3); P = 0.007). We tested the hypothesis that the disparate frequencies of these protective HLA alleles would be associated with a higher VRC at the population level in Mexico. Analysis of VRC in subjects in each cohort, matched for CD4(+) T-cell count, revealed that the VRC was indeed higher in the Mexican cohort (mean, 1.13 versus 1.03; P = 0.0025). Although CD4 counts were matched, viral loads remained significantly higher in the Mexican subjects (P = 0.04). This VRC difference was reflected by a significantly higher frequency in the Barbados cohort of HLA-B*27/57/58:01/81:01-associated Gag escape mutations previously shown to incur a fitness cost on the virus (P = 0.004), a difference between the two cohorts that remained statistically significant even in subjects not expressing these protective alleles (P = 0.01). These data suggest that viral set points and disease progression rates at the population level may be significantly influenced by the prevalence of protective HLA alleles such as HLA-B*27/57/58:01/81:01 and that CD4 count-based guidelines to initiate antiretroviral therapy may need to be modified accordingly, to optimize the effectiveness of treatment-for-prevention strategies and reduce HIV transmission rates to the absolute minimum. Immune control of HIV at an individual level is strongly influenced by the HLA class I genotype. HLA class I molecules mediating effective immune control, such as HLA-B*27 and HLA-B*57, are associated with the selection of escape mutants that reduce viral replicative capacity. The escape mutants selected in infected patients can be transmitted and affect the viral load and CD4 count in the recipient. These findings prompt the hypothesis that the frequency of protective alleles in a population may affect viral set points and rates of disease progression in that population. These studies in Mexico and Barbados, where the prevalence rates of protective HLA alleles are 8% and 34%, respectively, support this hypothesis. These data suggest that antiretroviral therapy (ART) treatment-for-prevention strategies will be less successful in populations such as those in Mexico, where viral loads are higher for a given CD4 count. Consideration may therefore usefully be given to ART initiation at higher absolute CD4 counts in such populations to optimize the impact of ART for prevention. Copyright © 2014 Juarez-Molina et al.

Treatment of HIV infection: Swedish recommendations 2009.

PubMed

Josephson, Filip; Albert, Jan; Flamholc, Leo; Gisslén, Magnus; Karlström, Olof; Moberg, Lars; Navér, Lars; Svedhem, Veronica; Svennerholm, Bo; Sönnerborg, Anders

2009-01-01

On 4 previous occasions, in 2002, 2003, 2005 and 2007, the Swedish Medical Products Agency (Läkemedelsverket) and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection. In November 2008, an expert group under the guidance of RAV once more revised the guidelines, of which this is a translation into English. The most important updates in the present guidelines include the following: (a) treatment initiation is now recommended at a CD4 cell count of approximately 350/microl; (b) new recommendations for first-line therapy: abacavir/lamivudine or tenofovir/emtricitabine in combination with efavirenz or a boosted protease inhibitor (PI/r); (c) an increased focus on reducing the use of antiretroviral drugs that may cause lipoatrophy; (d) an emphasis on quality assurance of HIV care through the use of InfCare HIV; (e) considerably altered recommendations for the initiation of antiretroviral therapy in children. All infants (<1 y) should start antiretroviral therapy, regardless of immune status. Also, absolute CD4+ cell counts, rather than percentage, may be used to guide treatment initiation in children above the age of 5 y.

Antiretroviral drug costs and prescription patterns in British Columbia, Canada: 1996-2011.

PubMed

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

2014-04-01

Treatment options and therapeutic guidelines have evolved substantially since highly active antiretroviral treatment (HAART) became the standard of HIV care in 1996. We conducted the present population-based analysis to characterize the determinants of direct costs of HAART over time in British Columbia, Canada. We considered individuals ever receiving HAART in British Columbia from 1996 to 2011. Linear mixed-effects regression models were constructed to determine the effects of demographic indicators, clinical stage, and treatment characteristics on quarterly costs of HAART (in 2010$CDN) among individuals initiating in different temporal periods. The least-square mean values were estimated by CD4 category and over time for each temporal cohort. Longitudinal data on HAART recipients (N = 9601, 17.6% female, mean age at initiation = 40.5) were analyzed. Multiple regression analyses identified demographics, treatment adherence, and pharmacological class to be independently associated with quarterly HAART costs. Higher CD4 cell counts were associated with modestly lower costs among pre-HAART initiators [least-square means (95% confidence interval), CD4 > 500: 4674 (4632-4716); CD4: 350-499: 4765 (4721-4809) CD4: 200-349: 4826 (4780-4871); CD4 <200: 4809 (4759-4859)]; however these differences were not significant among post-2003 HAART initiators. Population-level mean costs increased through 2006 and stabilized post-2003 HAART initiators incurred quarterly costs up to 23% lower than pre-2000 HAART initiators in 2010. Our results highlight the magnitude of the temporal changes in HAART costs, and disparities between recent and pre-HAART initiators. This methodology can improve the precision of economic modeling efforts by using detailed cost functions for annual, population-level medication costs according to the distribution of clients by clinical stage and era of treatment initiation.

Prevalence of Pulmonary tuberculosis and immunological profile of HIV co-infected patients in Northwest Ethiopia

PubMed Central

2012-01-01

Background In sub-Saharan Africa, as high as 2/3 of tuberculosis patients are HIV/AIDS co-infected and tuberculosis is the most common cause of death among HIV/AIDS patients worldwide. Tuberculosis and HIV co-infections are associated with special diagnostic and therapeutic challenges and constitute an immense burden on healthcare systems of heavily infected countries like Ethiopia. The aim of the study was to determine the prevalence of pulmonary tuberculosis and their immunologic profiles among HIV positive patients. Methods A cross sectional study was conducted among adult HIV-positive patients attending HIV/AIDS clinic of Gondar University Hospital. Clinical and laboratory investigations including chest x-ray and acid fast staining were used to identify tuberculosis cases. Blood samples were collected to determine CD4+ lymphocyte count. A structured questionnaire was used to collect socio-demographic characteristics of study subjects. The data was entered and analyzed using SPSS version 16 software. Results A total of 400 HIV positive study participants were enrolled. Thirty (7.5%, 95%CI: 5.2-10.6%) of the study participants were found to have pulmonary tuberculosis. In multivariate analysis, only CD4+ lymphocyte count (AOR = 2.9; 95% CI: 1.002-8.368) was found to be independently associated with tuberculosis-HIV co-infection. Individuals who had advanced WHO clinical stage were also statistically significant for co-infection. The mean CD4+ lymphocyte count of HIV mono-infected participants were 296 ± 192 Cells/mm3 and tuberculosis-HIV co-infected patients had mean CD4+ lymphocyte count of 199 ± 149 Cells/mm3 with p value of 0.007. Conclusions We found high prevalence of tuberculosis-HIV co-infection. Lower CD4+ lymphocyte count was found to be the only predicting factor for co-infection. Early detection of co-infection is very necessary to prolong their ART initiation time and by then strengthening their immune status. PMID:22738361

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.

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

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...

Dynamics of microbiological parameters, enzymatic activities and worm biomass production during vermicomposting of effluent treatment plant sludge of bakery industry.

PubMed

Yadav, Anoop; Suthar, S; Garg, V K

2015-10-01

This paper reports the changes in microbial parameters and enzymatic activities during vermicomposting of effluent treatment plant sludge (ETPS) of bakery industry spiked with cow dung (CD) by Eisenia fetida. Six vermibins containing different ratios of ETPS and CD were maintained under controlled laboratory conditions for 15 weeks. Total bacterial and total fungal count increased upto 7th week and declined afterward in all the bins. Maximum bacterial and fungal count was 31.6 CFU × 10(6) g(-1) and 31 CFU × 10(4) g(-1) in 7th week. Maximum dehydrogenase activity was 1921 μg TPF g(-1) h(-1) in 9th week in 100 % CD containing vermibin, whereas maximum urease activity was 1208 μg NH4 (-)N g(-1) h(-1) in 3rd week in 100 % CD containing vermibin. The enzyme activity and microbial counts were lesser in ETPS containing vermibins than control (100 % CD). The growth and fecundity of the worms in different vermibins were also investigated. The results showed that initially biomass and fecundity of the worms increased but decreased at the later stages due to non-availability of the palatable feed. This showed that quality and palatability of food directly affect biological parameters of the system.

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.

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol

PubMed Central

Cario, Gunnar; Rhein, Peter; Mitlöhner, Rita; Zimmermann, Martin; Bandapalli, Obul R.; Romey, Renja; Moericke, Anja; Ludwig, Wolf-Dieter; Ratei, Richard; Muckenthaler, Martina U.; Kulozik, Andreas E.; Schrappe, Martin; Stanulla, Martin; Karawajew, Leonid

2014-01-01

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75th percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72±3% versus 86±1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60±8% versus 78±4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22±3% versus 11±1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31±8% versus 11±3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118) PMID:23911702

High CD45 surface expression determines relapse risk in children with precursor B-cell and T-cell acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.

PubMed

Cario, Gunnar; Rhein, Peter; Mitlöhner, Rita; Zimmermann, Martin; Bandapalli, Obul R; Romey, Renja; Moericke, Anja; Ludwig, Wolf-Dieter; Ratei, Richard; Muckenthaler, Martina U; Kulozik, Andreas E; Schrappe, Martin; Stanulla, Martin; Karawajew, Leonid

2014-01-01

Further improvement of outcome in childhood acute lymphoblastic leukemia could be achieved by identifying additional high-risk patients who may benefit from intensified treatment. We earlier identified PTPRC (CD45) gene expression as a potential new stratification marker and now analyzed the prognostic relevance of CD45 protein expression. CD45 was measured by flow cytometry in 1065 patients treated according to the ALL-BFM-2000 protocol. The 75(th) percentile was used as cut-off to distinguish a CD45-high from a CD45-low group. As mean CD45 expression was significantly higher in T-cell acute lymphoblastic leukemia than in B-cell-precursor acute lymphoblastic leukemia (P<0.0001), the analysis was performed separately in both groups. In B-cell-precursor acute lymphoblastic leukemia we observed a significant association of a high CD45 expression with older age, high initial white blood cell count, ETV6/RUNX1 negativity, absence of high hyperdiploidy (P<0.0001), MLL/AF4 positivity (P=0.002), BCR/ABL1 positivity (P=0.007), prednisone poor response (P=0.002) and minimal residual disease (P<0.0001). In T-cell acute lymphoblastic leukemia we observed a significant association with initial white blood cell count (P=0.0003), prednisone poor response (P=0.01), and minimal residual disease (P=0.02). Compared to CD45-low patients, CD45-high patients had a lower event-free survival rate (B-cell-precursor acute lymphoblastic leukemia: 72 ± 3% versus 86 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 60 ± 8% versus 78 ± 4%, P=0.02), which was mainly attributable to a higher cumulative relapse incidence (B-cell-precursor acute lymphoblastic leukemia: 22 ± 3% versus 11 ± 1%, P<0.0001; T-cell acute lymphoblastic leukemia: 31 ± 8% versus 11 ± 3%, P=0.003) and kept its significance in multivariate analysis considering sex, age, initial white blood cell count, and minimal residual disease in B-cell-precursor- and T-cell acute lymphoblastic leukemia, and additionally presence of ETV6/RUNX1, MLL/AF4 and BCR/ABL1 rearrangements in B-cell-precursor acute lymphoblastic leukemia (P=0.002 and P=0.025, respectively). Consideration of CD45 expression may serve as an additional stratification tool in BFM-based protocols. (ClinicalTrials.gov identifier: NCT00430118).

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

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.

Estimating retention in HIV care accounting for patient transfers: A national laboratory cohort study in South Africa.

PubMed

Fox, Matthew P; Bor, Jacob; Brennan, Alana T; MacLeod, William B; Maskew, Mhairi; Stevens, Wendy S; Carmona, Sergio

2018-06-01

Systematic reviews have described high rates of attrition in patients with HIV receiving antiretroviral therapy (ART). However, migration and clinical transfer may lead to an overestimation of attrition (death and loss to follow-up). Using a newly linked national laboratory database in South Africa, we assessed national retention in South Africa's national HIV program. Patients receiving care in South Africa's national HIV program are monitored through regular CD4 count and viral load testing. South Africa's National Health Laboratory Service has maintained a database of all public-sector CD4 count and viral load results since 2004. We linked individual laboratory results to patients using probabilistic matching techniques, creating a national HIV cohort. Validation of our approach in comparison to a manually matched dataset showed 9.0% undermatching and 9.5% overmatching. We analyzed data on patients initiating ART in the public sector from April 1, 2004, to December 31, 2006, when ART initiation could be determined based on first viral load among those whose treatment followed guidelines. Attrition occurred on the date of a patient's last observed laboratory measure, allowing patients to exit and reenter care prior to that date. All patients had 6 potential years of follow-up, with an additional 2 years to have a final laboratory measurement to be retained at 6 years. Data were censored at December 31, 2012. We assessed (a) national retention including all laboratory tests regardless of testing facility and (b) initiating facility retention, where laboratory tests at other facilities were ignored. We followed 55,836 patients initiating ART between 2004 and 2006. At ART initiation, median age was 36 years (IQR: 30-43), median CD4 count was 150 cells/mm3 (IQR: 81-230), and 66.7% were female. Six-year initiating clinic retention was 29.1% (95% CI: 28.7%-29.5%). After allowing for transfers, national 6-year retention was 63.3% (95% CI: 62.9%-63.7%). Results differed little when tightening or relaxing matching procedures. We found strong differences in retention by province, ranging from 74.2% (95% CI: 73.2%-75.2%) in Western Cape to 52.2% (95% CI: 50.6%-53.7%) in Mpumalanga at 6 years. National attrition was higher among patients initiating at lower CD4 counts and higher viral loads, and among patients initiating ART at larger facilities. The study's main limitation is lack of perfect cohort matching, which may lead to over- or underestimation of retention. We also did not have data from KwaZulu-Natal province prior to 2010. In this study, HIV care retention was substantially higher when viewed from a national perspective than from a facility perspective. Our results suggest that traditional clinical cohorts underestimate retention.

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

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.

[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.

Operational challenges in delivering CD4 diagnostics in sub-Saharan Africa.

PubMed

Thairu, L; Katzenstein, D; Israelski, D

2011-07-01

Access to reliable and low cost CD4 T-cell enumeration to stage illness and monitor anti-retroviral therapy remains elusive in resource-limited settings. We report challenges in delivering CD4 testing using the microcapillary Fluorescence-Activated Cell Sorter (FACS) methodology (Guava EasyCD4 instrument Guava Technologies, Hayward) in Burkina Faso and Zimbabwe. Resources, instruments, reagents, and training were provided to local laboratories within the existing infrastructure and data on CD4 were collected from routine laboratory testing. Challenges encountered included frequent instrument breakdown; poor manufacturer maintenance; difficulties in managing reagent stocks; high technician turnover; reliance on antiquated data management systems; redundant service provision; and lack of repeat testing in male HIV+ patients and in patients with higher CD4 counts after initial staging. While adopting newer, less expensive technologies such as fluorescent platforms and point of care tests can facilitate access to lower cost CD4 testing, our experience suggests that supply chain, corporate commitment to implementation, and community factors also require consideration.

Cognitive function and neurodevelopmental outcomes in HIV-infected Children older than 1 year of age randomized to early versus deferred antiretroviral therapy: the PREDICT neurodevelopmental study.

PubMed

Puthanakit, Thanyawee; Ananworanich, Jintanat; Vonthanak, Saphonn; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; van der Lugt, Jasper; Kerr, Stephen J; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vibol, Ung; Pruksakaew, Kanchana; Suwarnlerk, Tulathip; Apornpong, Tanakorn; Ratanadilok, Kattiya; Paul, Robert; Mofenson, Lynne M; Fox, Lawrence; Valcour, Victor; Brouwers, Pim; Ruxrungtham, Kiat

2013-05-01

We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early versus deferred ART in the Pediatric Randomized to Early versus Deferred Initiation in Cambodia and Thailand (PREDICT) study. We now report neurodevelopmental outcomes. Two hundred eighty-four HIV-infected Thai and Cambodian children aged 1-12 years with CD4 counts between 15% and 24% and no AIDS-defining illness were randomized to initiate ART at enrollment ("early," n = 139) or when CD4 count became <15% or a Centers for Disease Control (CDC) category C event developed ("deferred," n = 145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration, Purdue Pegboard, Color Trails and Child Behavioral Checklist. Thai children (n = 170) also completed Wechsler Intelligence Scale (intelligence quotient) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n = 319). At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% versus 24%, P < 0.001) and a greater percentage of children with viral suppression (91% versus 40%, P < 0.001). Neurodevelopmental scores did not differ by arm, and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on intelligence quotient, Beery Visual Motor Integration, Binet memory and Child Behavioral Checklist. In HIV-infected children surviving beyond 1 year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15%-24% versus <15%, but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy.

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.

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.

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.

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.

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.

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.

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.

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

The incremental cost of switching from Option B to Option B+ for the prevention of mother-to-child transmission of HIV.

PubMed

O'Brien, Lisa; Shaffer, Nathan; Sangrujee, Nalinee; Abimbola, Taiwo O

2014-03-01

To estimate the incremental cost over 5 years of a policy switch from the Option B to the Option B+ protocol for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). Data from cost studies and other published sources were used to determine the cost, per woman and per cohort (1000 breastfeeding and 1000 non-breastfeeding women), of switching from Option B (maternal triple antiretroviral [ARV] regimen during pregnancy and breastfeeding plus daily nevirapine for the infant for 6 weeks) to Option B+ (maternal triple ARV regimen initiated during pregnancy and continued for life). The variables used to model the different scenarios were maternal CD4+ T lymphocyte (CD4+ cell) count (350-500 versus > 500 cells/µl), rate of decline in CD4+ cells (average, rapid, slow), breastfeeding status (yes, no) and breastfeeding duration (12, 18 or 24 months). For women with CD4+ cell counts of 350-500 cells/µl, the incremental cost per 1000 women was 157,345 United States dollars (US$) for breastfeeding women and US$ 92,813 for non-breastfeeding women. For women with CD4+ cell counts > 500 cells/µl, the incremental cost per 1000 women ranged from US$ 363,443 to US$ 484,591 for breastfeeding women and was US$ 605,739 for non-breastfeeding women. From a cost perspective, a policy switch from Option B to Option B+ is feasible in PMTCT programme settings where resources are currently being allocated to Option B.

Estimated mortality of adult HIV-infected patients starting treatment with combination antiretroviral therapy

PubMed Central

Yiannoutsos, Constantin Theodore; Johnson, Leigh Francis; Boulle, Andrew; Musick, Beverly Sue; Gsponer, Thomas; Balestre, Eric; Law, Matthew; Shepherd, Bryan E; Egger, Matthias

2012-01-01

Objective To provide estimates of mortality among HIV-infected patients starting combination antiretroviral therapy. Methods We report on the death rates from 122 925 adult HIV-infected patients aged 15 years or older from East, Southern and West Africa, Asia Pacific and Latin America. We use two methods to adjust for biases in mortality estimation resulting from loss from follow-up, based on double-sampling methods applied to patient outreach (Kenya) and linkage with vital registries (South Africa), and apply these to mortality estimates in the other three regions. Age, gender and CD4 count at the initiation of therapy were the factors considered as predictors of mortality at 6, 12, 24 and >24 months after the start of treatment. Results Patient mortality was high during the first 6 months after therapy for all patient subgroups and exceeded 40 per 100 patient years among patients who started treatment at low CD4 count. This trend was seen regardless of region, demographic or disease-related risk factor. Mortality was under-reported by up to or exceeding 100% when comparing estimates obtained from passive monitoring of patient vital status. Conclusions Despite advances in antiretroviral treatment coverage many patients start treatment at very low CD4 counts and experience significant mortality during the first 6 months after treatment initiation. Active patient tracing and linkage with vital registries are critical in adjusting estimates of mortality, particularly in low- and middle-income settings. PMID:23172344

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.

Uptake and outcome of combination antiretroviral therapy in men who have sex with men according to ethnic group: the UK CHIC Study.

PubMed

2012-04-15

We investigated differences in retention in HIV care and uptake of combination antiretroviral therapy (cART) and treatment outcomes between different ethnic men who have sex with men (MSM) groups. MSM subjects with known ethnicity and ≥1 day follow-up from 1996 to 2009 in the UK Collaborative HIV Cohort Study were included. Black and minority ethnic (BME) men were categorized as: black; Indian/Pakistani/Bangladeshi; other Asian/Oriental; and other/mixed. Logistic regression was used to identify factors associated with treatment initiation within the 6 months after each CD4 count. HIV viral load, CD4 counts, discontinuation/switch of a drug in the initial cART regimen, and development of a new AIDS event/death at 6 and 12 months were also analyzed. Of 16,406 MSM, 1818 (11.0%) were BME; 892 (49.1%) black, 139 (7.6%) Indian/Pakistani/Bangladeshi, 254 (13.9%) other Asian/Oriental, 532 (29.2%) other/mixed. The proportion of MSM with no follow-up after HIV diagnosis was higher among BME than white MSM (3.4% vs. 2.2%, P = 0.002). Permanent loss to follow-up was highest in the other/mixed and lowest in Indian/Pakistani/Bangladeshi groups (P = 0.02). Six thousand three hundred thirty-eight MSM initiated first cART from January 1, 2000, to January 1, 2009. In multivariable analyses, BME MSM were 18% less likely to initiate cART than white MSM with similar CD4 counts [adjusted odds ratio 0.82 (95% confidence interval: 0.74 to 0.91), P = 0.0001]. However, once on cART, there were no differences in virological, immunological, and clinical outcomes. This study demonstrates that despite BME MSM being a "minority within a minority" for those HIV infected, there are few ethnic disparities in access to and treatment outcomes in our setting.

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.

Risk factors for mortality in a south Indian population on generic antiretroviral therapy.

PubMed

Rupali, Priscilla; Mannam, Sam; Bella, Annie; John, Lydia; Rajkumar, S; Clarence, Peace; Pulimood, Susanne A; Samuel, Prasanna; Karthik, Rajiv; Abraham, Ooriapadickal Cherian; Mathai, Dilip

2012-12-01

Antiretroviral treatment (ART) programs from low-income countries utilizing standardized ART regimens, simplified approaches to clinical decision making and basic lab monitoring have reported high mortality rates. We determined the risk factors for mortality among HIV-infected adults following the initiation of ART from a single center in south India. ART-naive HIV-infected south Indian adults attending the Infectious Diseases clinic in a 2000-bed academic medical center in south India who were initiated on ART (generic, fixed-dose combinations) as per the national guidelines were followed up. Cases (32 patients who died) were compared with age and sex matched controls. Eight-hundred and twenty-two patients were started on ART from January 1, 2000 to December 31, 2008. The cumulative mortality was 6.8% (56/822). Among the cases mean age was 44 years, 18% were women and mean CD4 counts was 107 cells/microl. Among the controls mean age was 41 years, 18% were women and mean CD4 counts were 113 cells/microl. Stavudine based ART was predominant 62.5% in the cases vs 37.5% in the controls, followed by zidovudine based therapy in 31.2% of cases and 43.7% in the controls. Tenofovir based therapy was used in 6.2% of cases vs 18.7% in the controls. The commonest causes of death were drug toxicity 19%, advanced Acquired Immunodeficiency Syndrome (AIDS) in 37%, Immune Reconstitution Inflammatory Syndrome (IRIS) in 16%, non AIDS related deaths in 22% and malignancies 6%. In a univariate analysis, absolute lymphocyte count <1200 cells/cmm (p=0.03), development of immune reconstitution inflammatory syndrome (IRIS) (p=0.000) and mean CD4 cell count increase <75 cells/microl after 1 year of ART (p=0.001) were significantly associated with mortality. The mortality among our patients was comparable to that reported from other low-income countries. Earlier initiation of ART may reduce the high mortality rates observed.

Lack of pre-antiretroviral care and competition from traditional healers, crucial risk factors for very late initiation of antiretroviral therapy for HIV--a case-control study from eastern Uganda.

PubMed

Muhamadi, Lubega; Tumwesigye, Nazarius Mbona; Kadobera, Daniel; Marrone, Gaetano; Wabwire-Mangen, Fred; Pariyo, George; Peterson, Stefan; Ekström, Anna Mia

2011-01-01

Although WHO recommends starting antiretroviral treatment at a CD4 count of 350 cells/[µ]L, many Ugandan districts still struggle with large proportions of clients initiating ART very late at CD4<50 cells/[µ]L. This study seeks to establish crucial risk factors for very late ART initiation in eastern Uganda. All adult HIV-infected clients on ART in Iganga who enrolled between 2005 and 2009 were eligible for this case-control study. Clients who started ART at CD4 cell count of <50 cells/[µ]L (very late initiators) were classified as cases and 50-200 cells/[µ]L (late initiators) as control subjects. A total of 152 cases and 202 controls were interviewed. Multivariate analyses were performed to calculate adjusted odds ratios and 95% confidence intervals. Reported health system-related factors associated with very late ART initiation were stock-outs of antiretroviral drugs stock-outs (affecting 70% of the cases and none of the controls), competition from traditional/spiritual healers (AOR 7.8, 95 CI% 3.7-16.4), and lack of pre-ARV care (AOR 4.6, 95% CI: 2.3-9.3). Men were 60% more likely and subsistence farmers six times more likely (AOR 6.3, 95% CI: 3.1-13.0) to initiate ART very late. Lack of family support tripled the risk of initiating ART very late (AOR 3.3, 95% CI: 1.6-6.6). Policy makers should prevent ARV stock-outs though effective ARV procurement and supply chain management. New HIV clients should seek pre-ARV care for routine monitoring and determination of ART eligibility. ART services should be more affordable, accessible and user-friendly to make them more attractive than traditional healers.

Initial therapy with protease inhibitor-sparing regimens: evaluation of nevirapine and delavirdine.

PubMed

Conway, B

2000-06-01

We have compared the results (on-treatment analyses) of 2 randomized clinical trials of protease inhibitor-sparing regimens in drug-naive patients. In the INCAS (Italy, Netherlands, Canada, Australia) study, the mean decrease in plasma viral load over 52 weeks was 2.2 log(10) copies/mL in 40 patients who were receiving zidovudine/didanosine/nevirapine (18 [45%] had maximal suppression), with a mean increase in CD4 T cell counts of 139 cells/microL. In protocol 0021 Part II, the mean decrease in plasma viral load over 52 weeks was 2.1 log(10) copies/mL in 34 patients who were receiving zidovudine/lamivudine/delavirdine (20 [59%] had maximal suppression), with a mean increase in CD4 T cell counts of 88 cells/microL. The virologic and immunologic efficacy of the 2 triple-drug regimens are similar. Until results of long-term studies are available to establish whether a preferred approach to initial therapy exists, nonnucleoside reverse transcriptase inhibitors may be a valuable alternative to protease inhibitors in the initial therapy of antiretroviral-naive, moderately immunosuppressed patients.

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.

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.

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.

Cognitive Function and Neurodevelopmental Outcomes in HIV-Infected Children Older than 1 Year of Age Randomized to Early Versus Deferred Antiretroviral Therapy: The PREDICT Neurodevelopmental Study

PubMed Central

Puthanakit, Thanyawee; Ananworanich, Jintanat; Vonthanak, Saphonn; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; van der Lugt, Jasper; Kerr, Stephen J.; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Vibol, Ung; Pruksakaew, Kanchana; Suwarnlerk, Tulathip; Apornpong, Tanakorn; Ratanadilok, Kattiya; Paul, Robert; Mofenson, Lynne M.; Fox, Lawrence; Valcour, Victor; Brouwers, Pim; Ruxrungtham, Kiat

2013-01-01

Background We previously reported similar AIDS-free survival at 3 years in children who were >1 year old initiating antiretroviral therapy (ART) and randomized to early vs. deferred ART in the PREDICT Study. We now report neurodevelopmental outcomes. Methods 284 HIV-infected Thai and Cambodian children aged 1–12 years with CD4 counts between 15–24% and no AIDS-defining illness were randomized to initiate ART at enrollment (“early”, n=139) or when CD4 count became <15% or a CDC C event developed (“deferred”, n=145). All underwent age-appropriate neurodevelopment testing including Beery Visual Motor Integration (VMI), Purdue Pegboard, Color Trails and Child Behavioral Checklist (CBCL). Thai children (n=170) also completed Wechsler Intelligence Scale (IQ) and Stanford Binet Memory test. We compared week 144 measures by randomized group and to HIV-uninfected children (n=319). Results At week 144, the median age was 9 years and 69 (48%) of the deferred arm children had initiated ART. The early arm had a higher CD4 (33% vs. 24%, p<0.001) and a greater percentage of children with viral suppression (91% vs. 40%, p<0.001). Neurodevelopmental scores did not differ by arm and there were no differences in changes between arms across repeated assessments in time-varying multivariate models. HIV-infected children performed worse than uninfected children on IQ, Beery VMI, Binet memory and CBCL Conclusions In HIV-infected children surviving beyond one year of age without ART, neurodevelopmental outcomes were similar with ART initiation at CD4 15–24% vs. < 15%; but both groups performed worse than HIV-uninfected children. The window of opportunity for a positive effect of ART initiation on neurodevelopment may remain in infancy. PMID:23263176

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

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

Factors Associated with Timing of Initiation of Antiretroviral Therapy among HIV-1 Infected Adults in the Niger Delta Region of Nigeria

PubMed Central

Ogoina, Dimie

2015-01-01

Introduction Based on growing evidence mainly from countries outside Sub-Saharan Africa, the World Health Organisation (WHO) now recommends initiation of antiretroviral therapy (ART) in HIV-infected individuals in developing countries when CD4 cell count (CD4+) is ≤ 500cells/ul. Nigeria accounts for about 14% of the estimated HIV/AIDS burden in Sub-Saharan Africa. We evaluated the factors associated with timing of initiation of ART among treatment-ineligible HIV-infected adults from Nigeria. Methods We retrospectively reviewed the hospital records of ART ineligible HIV-infected adults who enrolled into HIV care between January 2008 and December 2012 at two major tertiary hospitals in Bayelsa State, South-South Nigeria. Demographic, clinical and laboratories data were obtained at presentation, at each subsequent visit at 6 monthly intervals and at time of initiation of ART. Cox proportional regression and Kaplan-Meier survival analysis were used to evaluate independent predictors of time to initiation of ART. Results Amongst the 280 study participants, 70.6% were females, 62.6% had CD4+ ≥500cells/ul, 48.4% had WHO HIV Stage 1 disease and 34.3% were lost to follow up. In a cohort of 180 participants followed up for ≥3months, participants with CD4+ of 351-500cells/ul and stage 2 disease were more likely to start ART earlier than those with CD4+ > 500cells/ul (Hazard ratio [HR]-1.7, 95% confidence interval [CI] of 1.0-2.9) and stage 1 disease (HR-2.3 (95% CI-1.3-4.2) respectively. HIV-infected adults with faster CD4+ decay required earlier ART initiation, especially in the first year of follow up. Conclusion ART-ineligible HIV-infected adults on follow up in South-South Nigeria are more likely to require earlier initiation of ART if they have stage 2 HIV disease or CD4+ ≤500cells/ul at presentation. Our findings suggest faster progression of HIV-disease in these groups of individuals and corroborate the growing evidence in support for earlier initiation of ART. PMID:25933356

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.

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.

Cost-effectiveness of initiating antiretroviral therapy at different points in TB treatment in HIV-TB co-infected ambulatory patients in South Africa

PubMed Central

Naidoo, Kogieleum; Grobler, Anneke C; Deghaye, Nicola; Reddy, Tarylee; Gengiah, Santhanalakshmi; Gray, Andrew; Karim, Salim Abdool

2015-01-01

Objective Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment improves survival in TB-HIV co-infected patients. In patients with CD4+ counts <50cells/mm3, there is a substantial clinical and survival benefit of early ART initiation. The purpose of this study was to assess the costs and cost effectiveness of starting ART at various time points during TB treatment in patients with CD4+ counts ≥50cells/mm3. Methods In the SAPiT trial, 642 HIV-TB co-infected patients were randomized to three arms, either receiving ART within 4 weeks of starting TB treatment (early treatment arm; Arm-1), after the intensive phase of TB treatment (late treatment arm; Arm-2), or after completing TB treatment (sequential arm; Arm-3). Direct healthcare costs were measured from a provider perspective using a micro-costing approach. The incremental cost per death averted was calculated using the trial outcomes. Results For patients with CD4+ count≥50cells/mm3, median monthly variable costs per patient were $116, $113 and $102 in Arms-1, -2 and -3, respectively. There were 12 deaths in 177 patients in Arm-1, 8 deaths in 180 patients in the Arm-2 and 19 deaths in 172 patients in Arm-3. While the costs were lower in Arm-3, it had a substantially higher mortality rate. The incremental cost per death averted associated with moving from Arm-3 to Arm-2 was $4199. There was no difference in mortality between Arm-1 and Arm-2, but Arm-1 was slightly more expensive. Conclusions Initiation of ART after the completion of the intensive phase of TB treatment is cost effective for patients with CD4+ counts≥50cells/mm3. PMID:26167618

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.

ART adherence, demographic variables and CD4 outcome among HIV-positive patients on antiretroviral therapy in Chennai, India.

PubMed

Safren, S A; Kumarasamy, N; James, R; Raminani, S; Solomon, S; Mayer, Kenneth H

2005-10-01

This is an analysis of available chart data recorded by HIV counselors and physicians on patient adherence and CD4 count in 304 patients with HIV who were prescribed antiretroviral therapy (ART) in Chennai, India. HIV counselors had categorized the majority of patients' adherence as 'regular' (74.3%), with a significant minority being categorized as 'irregular' (17.8%), or 'recently missed some doses' (6.9%). Those categorized as 'irregular' had significantly lower CD4 counts than those classified as 'regular'. Adherence was not associated with any demographic variable; however, it was associated with current CD4 and with change in CD4 since initiation of ART. This association was significant over and above the effects of time on ART. The most common reason for non-adherence was cost (32%), followed by the inability to return for a refill (i.e., patients who were unable or refused to obtain medicines elsewhere) (7.5%). These data suggest that although most patients in this Indian cohort reported regular adherence to ART, a subset admitted to less than regular adherence to ART, and those who admitted to less than regular adherence had worse CD4 outcomes. These data do not support concerns about adherence as a reason to withhold ART in developing countries, nor do they support claims that patients in India who struggle with adherence would be unwilling or unable to admit to non-adherence to health care professionals.

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.

A Lower Baseline CD4/CD8 T-Cell Ratio Is Independently Associated with Immunodiscordant Response to Antiretroviral Therapy in HIV-Infected Subjects

PubMed Central

Rosado-Sánchez, I.; Herrero-Fernández, I.; Álvarez-Ríos, A. I.; Genebat, M.; Abad-Carrillo, M. A.; Ruiz-Mateos, E.; Pulido, F.; González-García, J.; Montero, M.; Bernal-Morell, E.; Vidal, F.; Leal, M.

2017-01-01

ABSTRACT We explored if baseline CD4/CD8 T-cell ratio is associated with immunodiscordant response to antiretroviral therapy in HIV-infected subjects. Comparing immunodiscordant and immunoconcordant subjects matched by pretreatment CD4 counts, we observed a lower pretreatment CD4/CD8 T-cell ratio in immunodiscordant subjects. Furthermore, pretreatment CD4/CD8 T-cell ratio, but not CD4 counts, correlated with the main immunological alterations observed in immunodiscordants, including increased regulatory T-cell (Treg) frequency and T-cell turnover-related markers. Then, in a larger cohort, only baseline CD4/CD8 T-cell ratio was independently associated with immunodiscordance, after adjusting by the viral CXCR4-tropic HIV variants. Our results suggest that the CD4/CD8 T-cell ratio could be an accurate biomarker of the subjacent immunological damage triggering immunodiscordance. PMID:28559274

Dimethyl fumarate–induced lymphopenia in MS due to differential T-cell subset apoptosis

PubMed Central

Ghadiri, Mahtab; Rezk, Ayman; Li, Rui; Evans, Ashley; Luessi, Felix; Zipp, Frauke; Giacomini, Paul S.; Antel, Jack

2017-01-01

Objective: To examine the mechanism underlying the preferential CD8+ vs CD4+ T-cell lymphopenia induced by dimethyl fumarate (DMF) treatment of MS. Methods: Total lymphocyte counts and comprehensive T-cell subset analyses were performed in high-quality samples obtained from patients with MS prior to and serially following DMF treatment initiation. Random coefficient mixed-effects analysis was used to model the trajectory of T-cell subset losses in vivo. Survival and apoptosis of distinct T-cell subsets were assessed following in vitro exposure to DMF. Results: Best-fit modeling indicated that the DMF-induced preferential reductions in CD8+ vs CD4+ T-cell counts nonetheless followed similar depletion kinetics, suggesting a similar rather than distinct mechanism involved in losses of both the CD8+ and CD4+ T cells. In vitro, DMF exposure resulted in dose-dependent reductions in T-cell survival, which were found to reflect apoptotic cell death. This DMF-induced apoptosis was greater for CD8+ vs CD4+, as well as for memory vs naive, and conventional vs regulatory T-cell subsets, a pattern which mirrored preferential T-cell subset losses that we observed during in vivo treatment of patients. Conclusions: Differential apoptosis mediated by DMF may underlie the preferential lymphopenia of distinct T-cell subsets, including CD8+ and memory T-cell subsets, seen in treated patients with MS. This differential susceptibility of distinct T-cell subsets to DMF-induced apoptosis may contribute to both the safety and efficacy profiles of DMF in patients with MS. PMID:28377940

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

PubMed

Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

2015-01-01

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

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

Socio-economic status and time trends associated with early ART initiation following primary HIV infection in Montreal, Canada: 1996 to 2015.

PubMed

Mehraj, Vikram; Cox, Joseph; Lebouché, Bertrand; Costiniuk, Cecilia; Cao, Wei; Li, Taisheng; Ponte, Rosalie; Thomas, Réjean; Szabo, Jason; Baril, Jean-Guy; Trottier, Benoit; Côté, Pierre; LeBlanc, Roger; Bruneau, Julie; Tremblay, Cécile; Routy, Jean-Pierre

2018-02-01

Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study. The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs). Recently diagnosed HIV-infected adults were categorized as receiving early (vs. delayed) ART if ART was initiated within 180 days of the baseline visit. Associations between early ART initiation and socio-demographic, socio-economic and behavioural information were examined. Independent associations of factors linked with early ART initiation were determined using multivariable binary logistic regression analysis. A total of 348 participants had a documented date of HIV acquisition of <180 days. The median interquartile range (IQR) age of participants was 35 (28; 42) years and the majority were male (96%), having paid employment (63%), men who have sex with men (MSM) (78%) and one to four sexual partners in the last three months (70%). Participants presented with a median IQR HIV plasma viral load of 4.6 (3.7; 5.3) log 10 copies/ml, CD4 count of 510 (387; 660) cells/μl and were recruited in CMCs (52%) or UMCs (48%). Early ART initiation was observed in 47% of the participants and the trend followed a V-shaped curve with peaks in 1996 to 1997 (89%) and 2013 to 2015 (88%) with a dip in 2007 to 2009 (22%). Multivariable analyses showed that having a paid employment adjusted odds ratio (aOR: 2.43; 95% CI: 1.19, 4.95), lower CD4 count (aOR per 50 cell increase: 0.93; 95% CI: 0.87, 0.99) and care at UMCs (aOR: 2.03; 95% CI: 1.06 to 3.90) were independently associated with early ART initiation. Early ART initiation during primary HIV infection was associated with diminished biological prognostic factors and calendar time mirroring evolution of treatment guidelines. In addition, socio-economic factors such as having a paid employment, contribute to early ART initiation in the context of universal access to care in Canada. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

AIDS therapy with two, three or four agent combinations, applied in short sequences, differing from each other by drug rotation. I. First of two parts: a phase I trial equivalent, concerning five virostatics: AZT, ddI, ddC, acriflavine and an ellipticine analogue.

PubMed

Mathé, G; Pontiggia, P; Orbach-Arbouys, S; Triana, K; Ambetima, N; Morette, C; Hallard, M; Blanquet, D

1996-01-01

We have individually treated ten AIDS patients whose CD4 numbers were inferior to 200/mm3, with the five following HIV1 virostatics: a) azido-deoxythymidine (AZT), dideoxyinosine (ddI) and dideoxycytidine (ddC), which affect the same viral target, retrotranscriptase, b) acriflavine (ACF) and methyl-hydroxy-ellipticine (MHE) which we have discovered to be strong virostatics in vivo, in mice, against Friend's virus, and in man, against AZT resistant HIV1. We have shown that their combinations with AZT, hitting three viral targets, reduces in mice, the blood Friend's virus load below detectable level. Due to the short doubling time of HIV1, AIDS therapy must be continuous, and to allow the best tolerance, the five virostatic combinations were applied in short, three-week sequences, each differing as much as possible from the former and from the following one, due to drug rotation [1]. Among the ten patients, a) three received the two-drug combinations for 15 to 30 months, followed by the three-drug combinations, b) three received the three-drug combinations from the beginning, c) four received the four-drug combinations also from the beginning, two having less than 10 CD4/mm3 at initiation of treatment, and two having more than 100. The tolerance was remarkable: the only side-effect being macrocytosis. The application of the two-drug combination sequences maintained stable CD4 levels in two subjects whose viral load (the evaluation of which had became available) was, at the end of this period, of 4,486 and 39,238 RNA copies. The third subject who had received, an intensive UV irradiation for a psoriasis, presented an irreversible decrease in his CD4 count and a high viral load (1,352,495 RNA copies/mL) at the end of the two-drug period. Fifteen to 25 months after the shift to the three-drug combinations, the viral load decreased, from 39,328 to 13,291 in one of the non-UV irradiated subjects, and from 1,352,495 to 314,387 in the irradiated one. No subject had an increase in CD4 number. In the three patients having initially received the three-drug combinations, a very strong decrease of viral load was registered after periods of observation varying from 77 to 40 months, while the CD4 counts increased moderately in two subjects, and noticeably in the third (from 126 to 266). Out of the four subjects initially treated with four-drug combinations, the two with less than 10 CD4/mm3 had a moderate decrease in viral load in about three months, and the CD4 increased from 9 to 34/mm3 in one. But the two subjects, because of opportunistic infections and psychological reasons, abandoned their treatments. In the two subjects who had more than 100 CD4/mm2 at initiation of the four-drug combination treatment, the viral load decreased to undetectable levels after four months: but their CD4 counts, after some oscillations, had very moderately increased at the end of the observation period (respectively, from 200 to 222, and from 129 to 134). In practice, these results suggest the interest of conducting phase II or III studies of AIDS treatment protocols, starting with the four-drug combination model, and attempting to maintain the effect with the three-drug combination one. As for theoretical considerations, one must underline the contrast between the remarkable reduction of the viral load and the usually moderate increase of the CD4 counts. The study but not the trial has been interrupted, due to the unavailability of three antiproteases, saquinavir, ritonavir and indinavir, which are now introduced in the same type of combinations, one by one, in replacement of one of the studied agents as shown in figure 1. The effect of increasing the total number of virostatics from five to eight will be published in the second part of this article series.

Concurrent CMV and EBV DNAemia is significantly correlated with a delay in the response to HAART in treatment-naive HIV type 1-positive patients.

PubMed

Panagiotakis, Simeon H; Soufla, Giannoula; Baritaki, Stavroula; Sourvinos, George; Passam, Andreas; Zagoreos, Ioannis; Stavrianeas, Nikolaos; Spandidos, Demetrios A

2007-01-01

The purpose of this study was to assess the qualitative single and multiple herpes virus DNAemia in the peripheral blood leukocytes (PBLs) of HIV-1-positive patients and its impact on the response to highly active antiretroviral therapy (HAART) and immune reconstitution. All (163) HIV-1-positive patients attending "Syngros AIDS Referral Center" from November 2000 to February 2001 were recruited. CMV, HSV-1, HSV-2, EBV, and HHV-8 DNA were detected in PBLs by polymerase chain reaction (PCR). Patients' follow-up comprised regular measurements of CD4(+) T cell count and HIV-1 viral load (VL) for an average period of 21 months. Immune reconstitution was defined as an increase in the CD4 T cell count by above 200 cells/micro l, while response to HAART was defined as a decrease in HIV-1 VL to undetectable levels. Single and multiple herpetic DNAemia in PBLs was found to be significantly higher in HIV-1-positive patients compared to healthy controls (p < 0.02) for all the viruses detected apart from HSV-2, which was not detected in the PBLs of either population. Concurrent CMV and EBV DNAemia significantly correlates with a delay in the response to HAART (p = 0.033) in treatment-naive patients. Untreated patients with a CD4(+) T cell count <200 cells/micro l, and with either CMV or EBV DNAemia, presented a delayed increase in the CD4 count after initiation of HAART (p = 0.035 and p = 0.037 respectively), while multiple herpetic DNAemia in the above patients was borderline associated with immune reconstitution (p = 0.068). Conclusively, CMV and EBV DNAemia may be poor prognostic factors for the response to HAART in treatment-naive HIV-1 patients.

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.

Appraisal of the sensitising potential of orally and dermally administered mercaptobenzothiazole by a biphasic protocol of the local lymph node assay.

PubMed

Ahuja, Varun; Wanner, Reinhard; Platzek, Thomas; Stahlmann, Ralf

2009-10-01

Mercaptobenzothiazole (MBT) is used while manufacturing natural rubber products. Our study deals with assessing its allergenic potential following dermal and oral routes of exposure, using a biphasic local lymph node assay (LLNA). Female Balb/c mice were treated with MBT (dermally 3, 10, 30% concentrations in DMSO; orally 1, 10, 100 mg/kg doses in corn oil) on the back (dermal study) or through oral administration (oral study) on days 1-3 followed by auricular application of 3, 10 and 30% concentrations, respectively, on days 15-17. End points determined on day 19 included ear thickness, ear punch weight, lymph node weight, lymph node cell count, and lymphocyte subpopulations (CD4+, CD8+, CD45+). After dermal application of 3% or 10% solution, a significant increase in cell count and lymph node weight along with significant decrease in CD8+ cells was observed. After initial oral administration of 1 mg/kg, we noticed a significant amplification in cell count. Following oral administration of 10 mg/kg, we observed a similar increase in cell count and lymph node weight. The results of our study show that the modified biphasic LLNA protocol can be used to study the sensitising potential of a compound also following the oral route of exposure.

Retrospective analysis of antiretroviral therapy uptake and retention of male clients receiving methadone maintenance therapy in two provinces in Vietnam: potential synergy of the two therapies.

PubMed

Pham, Linh Thi Thuy; Kitamura, Akiko; Do, Hoa Mai; Lai, Kim Anh; Le, Nhan Tuan; Nguyen, Van Thi Thuy; Kato, Masaya

2017-02-17

Vietnam has a concentrated HIV epidemic with injection drug use being the dominant mode of HIV transmission. Vietnam has rapidly expanded antiretroviral therapy (ART) and methadone maintenance therapy (MMT). This study aims to analyze ART uptake and retention among male clients receiving MMT in Vietnam in the early phase of the MMT program. The male clients (age ≥18) who were newly enrolled in care or started ART at two HIV clinics in Hanoi (2009 to 2011) and three HIV clinics in Can Tho (2010 to 2012) were included for the analysis. The CD4 lymphocyte count at HIV care enrollment and ART initiation and retention on ART were retrospectively analyzed. The values of those receiving MMT were compared with the values of two groups: those in whom injection drug use (IDU) status was documented, but were not receiving MMT, and all male clients not receiving MMT. To analyze retention, survival analysis with log rank test and Cox proportional hazard model was used. During the study period, 663 adult men were newly enrolled in HIV care (237 had IDU status documented) and 456 initiated ART (167 had IDU status documented). Among those who initiated ART, 28 were receiving MMT. At care enrolment, those receiving MMT had a median CD4 count of 230 (IQR 57-308) cells/mm 3 , while men self-reporting IDU and not receiving MMT and all men not receiving MMT had a median CD4 count of 158 (IQR 50-370) cells/mm 3 and 143 (IQR 35-366) cells/mm 3 , respectively. At ART initiation, men receiving MMT had significantly higher CD4 count with median at 203 (IQR 64-290) cells/mm 3 than men self-reporting IDU and not receiving MMT (80, IQR 40-220, cells/mm 3 , p = 0.038) and all men not receiving MMT (76, IQR 20-199, cells/mm 3 , p = 0.009). Those receiving MMT had a significantly higher retention rate than those self-reporting IDU but not receiving MMT (hazard ratio = 0.18, p = 0.019) and men not receiving MMT (hazard ratio = 0.20, p = 0.041). Our analysis suggests that men receiving MMT in Vietnam are achieving relatively early uptake and high retention rates on ART. The findings support potential benefits of integrating MMT and ART services in Vietnam.

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 incremental cost of switching from Option B to Option B+ for the prevention of mother-to-child transmission of HIV

PubMed Central

Shaffer, Nathan; Sangrujee, Nalinee; Abimbola, Taiwo O

2014-01-01

Abstract Objective To estimate the incremental cost over 5 years of a policy switch from the Option B to the Option B+ protocol for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). Methods Data from cost studies and other published sources were used to determine the cost, per woman and per cohort (1000 breastfeeding and 1000 non-breastfeeding women), of switching from Option B (maternal triple antiretroviral [ARV] regimen during pregnancy and breastfeeding plus daily nevirapine for the infant for 6 weeks) to Option B+ (maternal triple ARV regimen initiated during pregnancy and continued for life). The variables used to model the different scenarios were maternal CD4+ T lymphocyte (CD4+ cell) count (350–500 versus > 500 cells/µl), rate of decline in CD4+ cells (average, rapid, slow), breastfeeding status (yes, no) and breastfeeding duration (12, 18 or 24 months). Findings For women with CD4+ cell counts of 350–500 cells/µl, the incremental cost per 1000 women was 157 345 United States dollars (US$) for breastfeeding women and US$ 92 813 for non-breastfeeding women. For women with CD4+ cell counts > 500 cells/µl, the incremental cost per 1000 women ranged from US$ 363 443 to US$ 484 591 for breastfeeding women and was US$ 605 739 for non-breastfeeding women. Conclusion From a cost perspective, a policy switch from Option B to Option B+ is feasible in PMTCT programme settings where resources are currently being allocated to Option B. PMID:24700975

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

CD4 Enumeration Technologies: A Systematic Review of Test Performance for Determining Eligibility for Antiretroviral Therapy

PubMed Central

Peeling, Rosanna W.; Sollis, Kimberly A.; Glover, Sarah; Crowe, Suzanne M.; Landay, Alan L.; Cheng, Ben; Barnett, David; Denny, Thomas N.; Spira, Thomas J.; Stevens, Wendy S.; Crowley, Siobhan; Essajee, Shaffiq; Vitoria, Marco; Ford, Nathan

2015-01-01

Background Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. Methods and Findings Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/μl, bias ranged from -35.2 to +13.1 cells/μl while at counts >350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. Conclusions A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed. PMID:25790185

Evaluation of rapid progressors in HIV infection as an extreme phenotype.

PubMed

Olson, Ashley D; Guiguet, Marguerite; Zangerle, Robert; Gill, John; Perez-Hoyos, Santiago; Lodi, Sara; Ghosn, Jade; Dorrucci, Maria; Johnson, Anne; Sannes, Mette; Moreno, Santiago; Porter, Kholoud

2014-09-01

Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently infected individuals is unclear. Using a cohort of patients with known dates of HIV-1 seroconversion (SC), CASCADE (Concerted Action on SeroConversion on AIDS and Death in Europe), we identified proportions experiencing nadir CD4 cell levels within 1 year of SC, and assessed their mean AIDS-free survival time at 10-year follow-up and hazard of AIDS/death, compared with those whose CD4 remained >500 cells per cubic millimeter. Follow-up was censored at December 31, 1996 to avoid bias due to combination antiretroviral therapy initiation. Of 4876 individuals, 2.8%, 7.3%, and 24.9% experienced ≥1 CD4 <100, 200, and 350 cells per cubic millimeter, respectively, within 1 year of SC. Minimum CD4 levels of 30, 166, 231, and 506 cells per cubic millimeter were experienced during this period by 1%, 5%, 10%, and 50% of individuals, respectively. Mean (95% confidence interval) AIDS-free survival at 10 years follow-up was 2.9 (2.3 to 3.6), 5.5 (5.0 to 6.1), 6.7 (6.5 to 7.0), 7.4 (7.2 to 7.6), and 8.1 (7.9 to 8.3), for those with minimum counts ≤100, 100-200, 200-350, 350-500, >500 cells per cubic millimeter, respectively. Using counts of >500 cells per cubic millimeter as reference, the hazard ratios (95% confidence interval) of AIDS/death were 15.0 (11.9 to 18.9), 3.6 (2.9 to 4.5), 2.1 (1.8 to 2.4), and 1.5 (1.3 to 1.7), respectively. The hazard ratio increased to 37.5 (26.5 to 53.1) when a minimum CD4 count <100 was confirmed within 1 year of SC. At least 1 CD4 ≤100 cells per cubic millimeter within the first year of SC identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype.

Plasma viraemia in HIV-positive pregnant women entering antenatal care in South Africa

PubMed Central

Myer, Landon; Phillips, Tamsin K; Hsiao, Nei-Yuan; Zerbe, Allison; Petro, Gregory; Bekker, Linda-Gail; McIntyre, James A; Abrams, Elaine J

2015-01-01

Introduction Plasma HIV viral load (VL) is the principle determinant of mother-to-child HIV transmission (MTCT), yet there are few data on VL in populations of pregnant women in sub-Saharan Africa. We examined the distribution and determinants of VL in HIV-positive women seeking antenatal care (ANC) in Cape Town, South Africa. Methods Consecutive HIV-positive pregnant women making their first antenatal clinic visit were recruited into a cross-sectional study of viraemia in pregnancy, including a brief questionnaire and specimens for VL testing and CD4 cell enumeration. Results & discussion Overall 5551 pregnant women sought ANC during the study period, of whom 1839 (33%) were HIV positive and 1521 (85%) were included. Approximately two-thirds of HIV-positive women in the sample (n=947) were not on antiretrovirals at the time of the first ANC visit, and the remainder (38%, n=574) had initiated antiretroviral therapy (ART) prior to conception. For women not on ART, the median VL was 3.98 log10 copies/mL; in this group, the sensitivity of CD4 cell counts ≤350 cells/µL in detecting VL>10,000 copies/mL was 64% and this increased to 78% with a CD4 threshold of ≤500 cells/µL. Among women on ART, 78% had VL<50 copies/mL and 13% had VL >1000 copies/mL at the time of their ANC visit. Conclusions VL >10,000 copies/mL was commonly observed in women not on ART with CD4 cell counts >350 cells/µL, suggesting that CD4 cell counts may not be adequately sensitive in identifying women at greatest risk of MTCT. A large proportion of women entering ANC initiated ART before conception, and in this group more than 10% had VL>1000 copies/mL despite ART use. VL monitoring during pregnancy may help to identify pregnancies that require additional clinical attention to minimize MTCT risk and improve maternal and child health outcomes. PMID:26154734

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

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.

Risk factors for late-stage HIV disease presentation at initial HIV diagnosis in Durban, South Africa.

PubMed

Drain, Paul K; Losina, Elena; Parker, Gary; Giddy, Janet; Ross, Douglas; Katz, Jeffrey N; Coleman, Sharon M; Bogart, Laura M; Freedberg, Kenneth A; Walensky, Rochelle P; Bassett, Ingrid V

2013-01-01

After observing persistently low CD4 counts at initial HIV diagnosis in South Africa, we sought to determine risk factors for late-stage HIV disease presentation among adults. We surveyed adults prior to HIV testing at four outpatient clinics in Durban from August 2010 to November 2011. All HIV-infected adults were offered CD4 testing, and late-stage HIV disease was defined as a CD4 count <100 cells/mm(3). We used multivariate regression models to determine the effects of sex, emotional health, social support, distance from clinic, employment, perceived barriers to receiving healthcare, and foregoing healthcare to use money for food, clothing, or housing ("competing needs to healthcare") on presentation with late-stage HIV disease. Among 3,669 adults screened, 830 were enrolled, newly-diagnosed with HIV and obtained a CD4 result. Among those, 279 (33.6%) presented with late-stage HIV disease. In multivariate analyses, participants who lived ≥5 kilometers from the test site [adjusted odds ratio (AOR) 2.8, 95% CI 1.7-4.7], reported competing needs to healthcare (AOR 1.7, 95% CI 1.2-2.4), were male (AOR 1.7, 95% CI 1.2-2.3), worked outside the home (AOR 1.5, 95% CI 1.1-2.1), perceived health service delivery barriers (AOR 1.5, 95% CI 1.1-2.1), and/or had poor emotional health (AOR 1.4, 95% CI 1.0-1.9) had higher odds of late-stage HIV disease presentation. Independent risk factors for late-stage HIV disease presentation were from diverse domains, including geographic, economic, demographic, social, and psychosocial. These findings can inform various interventions, such as mobile testing or financial assistance, to reduce the risk of presentation with late-stage HIV disease.

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.

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.

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.

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.

Is Clinical Practice Concordant with the Changes in Guidelines for Antiretroviral Therapy Initiation during Primary and Chronic HIV-1 Infection? The ANRS PRIMO and COPANA Cohorts

PubMed Central

Krastinova, Evguenia; Seng, Remonie; Yeni, Patrick; Viard, Jean-Paul; Vittecoq, Daniel; Lascoux-Combe, Caroline; Fourn, Erwan; Pahlavan, Golriz; Delfraissy, Jean François; Meyer, Laurence

2013-01-01

Objective Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France. Methods Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996–2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004–2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively. Results ART initiation during PHI dramatically decreased from 91% of patients in 1996–99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm3 in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm3. Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions. Conclusion HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients’ living conditions and physicians’ perceptions influence the decision to initiate treatment. PMID:23936509

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

Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

PubMed

2000-07-07

To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

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.

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.

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.

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

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.

CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1–infected individuals

PubMed Central

Ahuja, Sunil K; Kulkarni, Hemant; Catano, Gabriel; Agan, Brian K; Camargo, Jose F; He, Weijing; O'Connell, Robert J; Marconi, Vincent C; Delmar, Judith; Eron, Joseph; Clark, Robert A; Frost, Simon; Martin, Jeffrey; Ahuja, Seema S; Deeks, Steven G; Little, Susan; Richman, Douglas; Hecht, Frederick M; Dolan, Matthew J

2008-01-01

The basis for the extensive variability seen in the reconstitution of CD4+ T cell counts in HIV-infected individuals receiving highly active antiretroviral therapy (HAART) is not fully known. Here, we show that variations in CCL3L1 gene dose and CCR5 genotype, but not major histocompatibility complex HLA alleles, influence immune reconstitution, especially when HAART is initiated at <350 CD4+ T cells/mm3. The CCL3L1-CCR5 genotypes favoring CD4+ T cell recovery are similar to those that blunted CD4+ T cell depletion during the time before HAART became available (pre-HAART era), suggesting that a common CCL3L1-CCR5 genetic pathway regulates the balance between pathogenic and reparative processes from early in the disease course. Hence, CCL3L1-CCR5 variations influence HIV pathogenesis even in the presence of HAART and, therefore, may prospectively identify subjects in whom earlier initiation of therapy is more likely to mitigate immunologic failure despite viral suppression by HAART. Furthermore, as reconstitution of CD4+ cells during HAART is more sensitive to CCL3L1 dose than to CCR5 genotypes, CCL3L1 analogs might be efficacious in supporting immunological reconstitution. PMID:18376407

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.

HAART slows progression to anal cancer in HIV-infected MSM.

PubMed

Duncan, Katrina C; Chan, Keith J; Chiu, Connie G; Montaner, Julio S G; Coldman, Andy J; Cescon, Angela; Au-Yeung, Christopher G; Wiseman, Sam M; Hogg, Robert S; Press, Natasha M

2015-01-28

Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (<1996) were compared with those treated later (1996-2008). Anal cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/μl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/μl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/μl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

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

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.

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.

Factors associated with loss to follow-up among women in Option B+ PMTCT programme in northeast Ethiopia: a retrospective cohort study.

PubMed

Mitiku, Israel; Arefayne, Mastewal; Mesfin, Yonatal; Gizaw, Muluken

2016-01-01

Ethiopia has recently adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women (Option B+ strategy), regardless of CD4 count or clinical stage. However, the exact timing and predictors of loss to follow-up (LFU) are unknown. Thus, we examined the levels and determinants of LFU under Option B+ among pregnant and breastfeeding women initiated on lifelong ART for prevention of mother-to-child transmission (PMTCT) in Ethiopia. We conducted a retrospective cohort study among 346 pregnant and breastfeeding women who started ART at 14 public health facilities in northeast Ethiopia from March 2013 to April 2015. We defined LFU as 90 days since the last clinic visit among those not known to have died or transferred out. We used Kaplan-Meier and Cox proportional hazards regression to estimate cumulative LFU and identify the predictors of LFU, respectively. Of the 346 women included, 88.4% were pregnant and the median follow-up was 13.7 months. Overall, 57 (16.5%) women were LFU. The cumulative proportions of LFU at 6, 12 and 24 months were 11.9, 15.7 and 22.6%, respectively. The risk of LFU was higher in younger women (adjusted hazard ratio (aHR) 18 to 24 years/30 to 40 years: 2.3; 95% confidence interval (CI): 1.2 to 4.5), in those attending hospitals compared to those attending health centres (aHR: 1.8; 95% CI: 1.1 to 3.2), in patients starting ART on the same day of diagnosis (aHR: 1.85; 95% CI: 1.1 to 3.2) and missing CD4 cell counts at ART initiation (aHR: 2.3; 95% CI: 1.2 to 4.4). The level of LFU we found in this study is comparable with previous findings from other resource-limited settings. However, high early LFU shortly after ART initiation is still a major problem. LFU was high among younger women, those initiating ART on the day of HIV diagnosis, those missing baseline CD4 count and those attending hospitals. Thus, targeted HIV care and treatment programmes for these patients should be part of future interventions to improve retention in care under the Option B+ PMTCT programme.

Review of policy and status of implementation of collaborative HIV-TB activities in 23 high-burden countries.

PubMed

Gupta, S; Granich, R; Date, A; Lepere, P; Hersh, B; Gouws, E; Samb, B

2014-10-01

Issuance of national policy guidance is a critical step to ensure quality HIV-TB (human immunodeficiency virus-tuberculosis) coordination and programme implementation. From the database of the Joint United Nations Programme on HIV/AIDS (UNAIDS), we reviewed 62 national HIV and TB guidelines from 23 high-burden countries for recommendations on HIV testing for TB patients, criteria for initiating antiretroviral therapy (ART) and the Three I's for HIV/TB (isoniazid preventive treatment [IPT], intensified TB case finding and TB infection control). We used UNAIDS country-level programme data to determine the status of implementation of existing guidance. Of the 23 countries representing 89% of the global HIV-TB burden, Brazil recommends ART irrespective of CD4 count for all people living with HIV, and four (17%) countries recommend ART at the World Health Organization (WHO) 2013 guidelines level of CD4 count ⩿500 cells/mm(3) for asymptomatic persons. Nineteen (83%) countries are consistent with WHO 2013 guidelines and recommend ART for HIV-positive TB patients irrespective of CD4 count. IPT is recommended by 16 (70%) countries, representing 67% of the HIV-TB burden; 12 recommend symptom-based screening alone for IPT initiation. Guidelines from 15 (65%) countries with 79% of the world's HIV-TB burden include recommendations on HIV testing and counselling for TB patients. Although uptake of ART, HIV testing for TB patients, TB screening for people living with HIV and IPT have increased significantly, progress is still limited in many countries. There is considerable variance in the timing and content of national policies compared with WHO guidelines. Missed opportunities to implement new scientific evidence and delayed adaptation of existing WHO guidance remains a key challenge for many countries.

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.

Cost-Effectiveness of HIV Screening in STD Clinics, Emergency Departments, and Inpatient Units: A Model-Based Analysis

PubMed Central

Prabhu, Vimalanand S.; Farnham, Paul G.; Hutchinson, Angela B.; Soorapanth, Sada; Heffelfinger, James D.; Golden, Matthew R.; Brooks, John T.; Rimland, David; Sansom, Stephanie L.

2011-01-01

Background Identifying and treating persons with human immunodeficiency virus (HIV) infection early in their disease stage is considered an effective means of reducing the impact of the disease. We compared the cost-effectiveness of HIV screening in three settings, sexually transmitted disease (STD) clinics serving men who have sex with men, hospital emergency departments (EDs), settings where patients are likely to be diagnosed early, and inpatient diagnosis based on clinical manifestations. Methods and Findings We developed the Progression and Transmission of HIV/AIDS model, a health state transition model that tracks index patients and their infected partners from HIV infection to death. We used program characteristics for each setting to compare the incremental cost per quality-adjusted life year gained from early versus late diagnosis and treatment. We ran the model for 10,000 index patients for each setting, examining alternative scenarios, excluding and including transmission to partners, and assuming HAART was initiated at a CD4 count of either 350 or 500 cells/µL. Screening in STD clinics and EDs was cost-effective compared with diagnosing inpatients, even when including only the benefits to the index patients. Screening patients in STD clinics, who have less-advanced disease, was cost-effective compared with ED screening when treatment with HAART was initiated at a CD4 count of 500 cells/µL. When the benefits of reduced transmission to partners from early diagnosis were included, screening in settings with less-advanced disease stages was cost-saving compared with screening later in the course of infection. The study was limited by a small number of observations on CD4 count at diagnosis and by including transmission only to first generation partners of the index patients. Conclusions HIV prevention efforts can be advanced by screening in settings where patients present with less-advanced stages of HIV infection and by initiating treatment with HAART earlier in the course of infection. PMID:21625489

Incidence rate of Kaposi sarcoma in HIV-infected patients on antiretroviral therapy in Southern Africa: a prospective multi-cohort study

PubMed Central

Rohner, Eliane; Valeri, Fabio; Maskew, Mhairi; Prozesky, Hans; Rabie, Helena; Garone, Daniela; Dickinson, Diana; Chimbetete, Cleophas; Lumano-Mulenga, Priscilla; Sikazwe, Izukanji; Wyss, Natascha; Clough-Gorr, Kerri M.; Egger, Matthias; Chi, Benjamin H.; Bohlius, Julia

2014-01-01

Background The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa. Methods We included patient data of six ART programs in Botswana, South Africa, Zambia, and Zimbabwe. We estimated KS incidence rates in patients on ART measuring time from 30 days after ART initiation to KS diagnosis, last follow-up visit, or death. We assessed risk factors (age, sex, calendar year, WHO stage, tuberculosis, and CD4 counts) using Cox models. Findings We analyzed data from 173,245 patients (61% female, 8% children aged <16 years) who started ART between 2004 and 2010. 564 incident cases were diagnosed during 343,927 person-years (pys). KS incidence rate overall was 164/100,000 pys (95% confidence interval [CI] 151–178). The incidence rate was highest 30 to 90 days after ART initiation (413/100,000 pys; 95% CI 342–497) and declined thereafter (86/100,000 pys[95% CI 71–105]>2 years after ART initiation). Male sex (adjusted hazard ratio [HR] 1.34; 95% CI 1.12–1.61), low current CD4 counts (≥500 cells/µL versus <50 cells/µL, adjusted HR 0.36; 95% CI 0.23–0.55) and age (5 to 9 years versus 30 to 39 years, adjusted HR 0.20; 95% CI 0.05–0.79) were relevant risk factors for developing KS. Interpretation Despite ART, KS risk in HIV-infected persons in Southern Africa remains high. Early HIV testing and maintaining high CD4 counts is needed to further reduce KS-related morbidity and mortality. PMID:25393941

Physician Decisions to Defer Antiretroviral Therapy in Key Populations: Implications for Reducing Human Immunodeficiency Virus Incidence and Mortality in Malaysia

PubMed Central

Ferro, Enrico G.; Culbert, Gabriel J.; Wickersham, Jeffrey A.; Marcus, Ruthanne; Steffen, Alana D.; Pauls, Heather A.; Westergaard, Ryan P.; Lee, Christopher K.; Kamarulzaman, Adeeba

2017-01-01

Abstract Background. Antiretroviral therapy (ART) is recommended for all people living with human immunodeficiency virus (HIV), yet physician attitudes and prescribing behaviors toward members of key risk populations may limit ART access and undermine treatment as prevention strategies. Methods. Physicians in Malaysia (N = 214) who prescribe antiretroviral therapy (ART) responded in an Internet-based survey to hypothetical clinical scenarios of HIV patients, varying by key risk population and CD4+ T-cell count, on whether they would initiate or defer ART compared with a control patient with sexually acquired HIV. Results. The proportion of physicians who would defer ART in patients with advanced HIV (CD4 = 17 cells/μL) was significantly higher (P < .0001) for 4 key populations, including people who inject drugs ([PWID] 45.3%) or consume alcohol (42.1%), released prisoners (35.0%), and those lacking social support (26.6%), compared with a control patient (4.2%). People who inject drugs with advanced HIV (CD4 = 17 cells/μL) were 19-fold (adjusted odds ratio [AOR] = 18.9; 95% confidence interval [CI], 9.8–36.5) more likely to have ART deferred compared with the control. This effect was partially mitigated for PWID receiving methadone (AOR = 2.9; 95% CI, 1.5–5.7). At the highest CD4+ T-cell count (CD4 = 470 cells/μL), sex workers (AOR = 0.55; 95% CI, .44–.70) and patients with an HIV-uninfected sexual partner (AOR = 0.43; 95% CI, .34–.57) were significantly less likely to have ART deferred. Conclusions. Physicians who prescribe antiretroviral therapy in Malaysia may defer ART in some key populations including PWID and released prisoners, regardless of CD4+ T-cell count, which may help to explain very low rates of ART coverage among PWID in Malaysia. Reducing HIV incidence and mortality in Malaysia, where HIV is concentrated in PWID and other key populations, requires clinician-level interventions and monitoring physician adherence to international evidence-based treatment guidelines. PMID:28480230

Primary HIV infection: a medical and public health emergency requiring rapid specialist management.

PubMed

Fidler, Sarah; Fox, Julie

2016-04-01

Primary HIV infection (PHI) refers to the first six months following HIV acquisition and represents a unique opportunity for expedited diagnosis, and consideration of rapid antiretroviral therapy (ART) initiation to improve immune function, reduce the size of the viral reservoir and limit the risk of onward viral transmission. Failure to diagnose and rapidly treat individuals with PHI has significant individual and public health implications. The Strategic Timing of AntiRetroviral Treatment trial recently identified a clinical benefit of immediate ART over deferral of treatment according to CD4 count threshold, and has led to rapid changes in World Health Organization and specialist national guidelines. For all individuals living with HIV, the offer of immediate therapy irrespective of CD4 count is now recommended. This paper summarises the presentation and management of PHI, incorporating current research and guideline changes and discusses the role of PHI in onward transmission. © 2016 Royal College of Physicians.

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.

Evaluating the care cascade after antiretroviral therapy initiation in Latin America

PubMed Central

Wolff, Marcelo J; Cortes, Claudia P; Mejìa, Fernando A; Padgett, Denis; Belaunzarán-Zamudio, Pablo; Grinsztejn, Beatriz; Giganti, Mark J; McGowan, Catherine C; Rebeiro, Peter F

2018-01-01

Accelerating antiretroviral therapy (ART) administration, improving retention, and achieving viral suppression in low- and middle-income countries must be prioritized. We evaluated trends and disparities in these milestones in a large Latin American cohort. Adults starting ART (ARTstart) from 2003 to 2014 at Caribbean, Central, and South America network for HIV epidemiology sites were assessed for care cascade outcomes: CD4 cell count >200 cells/mm3 at ARTstart; retention (≥1 visit at one year after ARTstart); viral suppression (≥1 HIV-1 RNA <200 copies/ml at one year after ARTstart). Modified Poisson regression provided adjusted prevalence ratios by age, gender, and HIV transmission risk, accounting for site and year of ARTstart. Proportions achieving ARTstart and suppression improved over time (p < 0.05). Older age was associated with better retention and viral suppression, but not ARTstart at CD4 cell count >200 cells/mm3. Females and men who have sex with men (MSM) were more likely to have CD4 cell count >200 cells/mm3 at ARTstart. Injection drug users (IDUs) were less likely to be retained while MSM were more likely to achieve viral suppression (all p <0.05). Despite improvements in these outcomes over the course of a decade in this cohort, significant disparities existed, disadvantaging younger patients, men, and IDUs. These gaps indicate continued progress in providing early diagnosis and ARTstart remain critical. PMID:28618980

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.

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.

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.

PubMed

Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John; Cambiano, Valentina; Chindelevitch, Leonid; Cori, Anne; Hontelez, Jan A C; Humair, Salal; Kerr, Cliff C; Klein, Daniel J; Mishra, Sharmistha; Mitchell, Kate M; Nichols, Brooke E; Vickerman, Peter; Bakker, Roel; Bärnighausen, Till; Bershteyn, Anna; Bloom, David E; Boily, Marie-Claude; Chang, Stewart T; Cohen, Ted; Dodd, Peter J; Fraser, Christophe; Gopalappa, Chaitra; Lundgren, Jens; Martin, Natasha K; Mikkelsen, Evelinn; Mountain, Elisa; Pham, Quang D; Pickles, Michael; Phillips, Andrew; Platt, Lucy; Pretorius, Carel; Prudden, Holly J; Salomon, Joshua A; van de Vijver, David A M C; de Vlas, Sake J; Wagner, Bradley G; White, Richard G; Wilson, David P; Zhang, Lei; Blandford, John; Meyer-Rath, Gesine; Remme, Michelle; Revill, Paul; Sangrujee, Nalinee; Terris-Prestholt, Fern; Doherty, Meg; Shaffer, Nathan; Easterbrook, Philippa J; Hirnschall, Gottfried; Hallett, Timothy B

2014-01-01

New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per μL or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. We used several independent mathematical models in four settings-South Africa (generalised epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μL or less, or all HIV-positive adults, compared with the previous (2010) recommendation of initiation with CD4 counts of 350 cells per μL or less. We assessed costs from a health-system perspective, and calculated the incremental cost (in US$) per disability-adjusted life-year (DALY) averted to compare competing strategies. Strategies were regarded very cost effective if the cost per DALY averted was less than the country's 2012 per-head gross domestic product (GDP; South Africa: $8040; Zambia: $1425; India: $1489; Vietnam: $1407) and cost effective if the cost per DALY averted was less than three times the per-head GDP. In South Africa, the cost per DALY averted of extending eligibility for antiretroviral therapy to adult patients with CD4 counts of 500 cells per μL or less ranged from $237 to $1691 per DALY averted compared with 2010 guidelines. In Zambia, expansion of eligibility to adults with a CD4 count threshold of 500 cells per μL ranged from improving health outcomes while reducing costs (ie, dominating the previous guidelines) to $749 per DALY averted. In both countries results were similar for expansion of eligibility to all HIV-positive adults, and when substantially expanded treatment coverage was assumed. Expansion of treatment coverage in the general population was also cost effective. In India, the cost for extending eligibility to all HIV-positive adults ranged from $131 to $241 per DALY averted, and in Vietnam extending eligibility to patients with CD4 counts of 500 cells per μL or less cost $290 per DALY averted. In concentrated epidemics, expanded access for key populations was also cost effective. Our estimates suggest that earlier eligibility for antiretroviral therapy is very cost effective in low-income and middle-income settings, although these estimates should be revisited when more data become available. Scaling up antiretroviral therapy through earlier eligibility and expanded coverage should be considered alongside other high-priority health interventions competing for health budgets. Bill & Melinda Gates Foundation, WHO. Copyright © 2014 Eaton et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.

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.

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.

Receipt and timing of HIV drug resistance testing in six U.S. jurisdictions.

PubMed

Dasgupta, Sharoda; Hall, H Irene; Hernandez, Angela L; Ocfemia, M Cheryl Bañez; Saduvala, Neeraja; Oster, Alexandra M

2017-12-01

The Department of Health and Human Services recommends drug resistance testing at linkage to HIV care. Because receipt and timing of testing are not well characterized, we examined testing patterns among persons with diagnosed HIV who are linked to care. Using surveillance data in six jurisdictions for persons aged ≥13 years with HIV infection diagnosed in 2013, we assessed the proportion receiving testing, and among these, the proportion receiving testing at linkage. Multivariable log-binomial regression modeling estimated associations between selected characteristics and receipt of testing (1) overall, and (2) at linkage among those tested. Of 9,408 persons linked to care, 66% received resistance testing, among whom 68% received testing at linkage. Less testing was observed among male persons who inject drugs (PWID), compared with men who have sex with men (adjusted prevalence ratio [aPR]: 0.88; 95% confidence interval [CI]: 0.81-0.97) and persons living in areas with population <500,000 compared with those in areas with population ≥2,500,000 (aPR: 0.88; CI: 0.84-0.93). In certain jurisdictions, testing was lower for persons with initial CD4 counts ≥500 cells/mm 3 , compared with those with CD4 counts <200 cells/mm 3 (aPR range: 0.80-0.85). Of those tested, testing at linkage was lower among male PWID (aPR: 0.85; CI: 0.75-0.95) and, in some jurisdictions, persons with CD4 counts ≥500 cells/mm 3 (aPR range: 0.63-0.73). Two-thirds of persons with diagnosed HIV who were linked to care received resistance testing, and most received testing at linkage as recommended. Improving receipt and timing of testing among male PWID, persons in less populous settings, and in all jurisdictions, regardless of CD4 count, may improve care outcomes.

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.

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

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.

Late HIV diagnosis is a major risk factor for intensive care unit admission in HIV-positive patients: a single centre observational cohort study

PubMed Central

2013-01-01

Background HIV positive patients are at risk of infectious and non-infectious complications that may necessitate intensive care unit (ICU) admission. While the characteristics of patients requiring ICU admission have been described previously, these studies did not include information on the denominator population from which these cases arose. Methods We conducted an observational cohort study of ICU admissions among 2751 HIV positive patients attending King’s College Hospital, South London, UK. Poisson regression models were used to identify factors associated with ICU admission. Results The overall incidence rate of ICU admission was 1.0 [95% CI 0.8, 1.2] per 100 person-years of follow up, and particularly high early (during the first 3 months) following HIV diagnosis (12.4 [8.7, 17.3] per 100 person-years compared to 0.37 [0.27, 0.50] per 100 person-years thereafter; incidence rate ratio 33.5 [23.4, 48.1], p < 0.001). In time-updated analyses, AIDS and current CD4 cell counts of less than 200 cells/mm3 were associated with an increased incidence of ICU admission while receipt of combination antiretroviral therapy (cART) was associated with a reduced incidence of ICU admission. Late HIV diagnosis (initial CD4 cell count <350 or AIDS within 3 months of HIV diagnosis) applied to 81% of patients who were first diagnosed HIV positive during the study period and who required ICU admission. Late HIV diagnosis was significantly associated with ICU admission in the first 3 months following HIV diagnosis (adjusted incidence rate ratio 8.72, 95% CI 2.76, 27.5). Conclusions Late HIV diagnosis was a major risk factor for early ICU admission in our cohort. Earlier HIV diagnosis allowing cART initiation at CD4 cell counts of 350 cells/mm3 is likely to have a significant impact on the need for ICU care. PMID:23331544

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.

[Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

PubMed

Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

2013-01-01

A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

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.

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

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.

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/

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.

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

Intestinal parasitosis in relation to CD4+T cells levels and anemia among HAART initiated and HAART naive pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia.

PubMed

Mengist, Hylemariam Mihiretie; Taye, Bineyam; Tsegaye, Aster

2015-01-01

Intestinal parasites (IPs) are major concerns in most developing countries where HIV/AIDS cases are concentrated and almost 80% of AIDS patients die of AIDS-related infections. In the absence of highly active antiretroviral therapy (HAART), HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic and other intestinal parasites. The aim of the study was to determine the prevalence of intestinal parasites in relation to CD4+ T cells levels and anemia among HAART initiated and HAART naïve pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia. A prospective comparative cross-sectional study was conducted among HAART initiated and HAART naive pediatric HIV/AIDS patients attending a model ART center at Zewditu Memorial Hospital between August 05, 2013 and November 25, 2013. A total of 180 (79 HAART initiated and 101 HAART naïve) children were included by using consecutive sampling. Stool specimen was collected and processed using direct wet mount, formol-ether concentration and modified Ziehl-Neelsen staining techniques. A structured questionnaire was used to collect data on socio-demographic and associated risk factors. CD4+ T cells and complete blood counts were performed using BD FACScalibur and Cell-Dyn 1800, respectively. The data was analyzed by SPSS version 16 software. Logistic regressions were applied to assess any association between explanatory factors and outcome variables. P values < 0.05 were taken as statistically significant. The overall prevalence of IPs was 37.8% where 27.8% of HAART initiated and 45.5% of HAART naive pediatric HIV/AIDS patients were infected (p < 0.05). Cryptosporidium species, E. histolytica/dispar, Hook worm and Taenia species were IPs associated with CD4+ T cell counts <350 cells/μμL in HAART naive patients. The overall prevalence of anemia was 10% in HAART and 31.7% in non-HAART groups. Hook worm, S. stercoralis and H. nana were helminthes significantly associated with anemia in non-HAART patients [AOR, 95% CI: 4.5(1.3, 15.2), P< 0.05]. The prevalence of IPs in non-HAART patients was significantly associated with eating unwashed/raw fruit [AOR, 95%CI: 6.3(1.2, 25.6), P<0.05], open field defecation [AOR, 95%CI: 9.3(1.6, 53.6), P<0.05] and diarrhea [AOR, 95%CI: 5.2(1.3, 21.3), P<0.05]. IPs significantly increased in rural residents [AOR, 95%CI: 0.4(0.1, 0.9, P<0.05)]. The overall prevalence of intestinal parasites significantly differed by HAART status and cryptosporidium species were found only in HAART naïve patients with low CD4+ T cell counts. Anemia was also more prevalent and significantly associated with IPs in non-HAART patients. This study identified some environmental and associated risk factors for intestinal parasitic infections. Therefore, Public health measures should continue to emphasize the importance of environmental and personal hygiene to protect HIV/AIDS patients from infections with intestinal parasites and maximize the benefits of HAART.

Human papillomavirus 16 (HPV16) and HPV52 E6-specific immunity in HIV-infected adults on combination antiretroviral therapy.

PubMed

Leng, C Y; Low, H C; Chua, L L; Chong, M L; Sulaiman, H; Azwa, I; Roberts, J M; Kamarulzaman, A; Rajasuriar, R; Woo, Y L

2017-05-01

Human papillomavirus (HPV)-associated cancers disproportionately affect those infected with HIV despite effective combination antiretroviral therapy (cART). The primary aim of this study was to quantify HPV16 and HPV52 E6-specific interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) T-cell responses, a correlate of protective immunity, in the first year following cART initiation and subsequently in those patients with suboptimal (sIR) and optimal (oIR) immune reconstitution. Ninety-four HIV-infected patients were recruited to the study; a longitudinal cohort of patients recruited just prior to commencing cART and followed up for 48 weeks (n = 27), and a cross-sectional cohort (n = 67) consisting of patients with sIR (CD4 T-cell count < 350 cells/μL) and oIR (CD4 T-cell count > 500 cells/μL) after a minimum of 2 years on cART. Controls (n = 29) consisted of HIV-negative individuals. IFN-γ ELISPOT responses against HPV16 and HPV52 E6 were correlated to clinical characteristics, anal and oral HPV carriage, T-cell maturational subsets, markers of activation, senescence and T-regulatory cells. HPV16 and HPV52 E6-specific T-cell responses were detected in only one of 27 patients (3.7%) during the initial phase of immune recovery. After at least 2 years of cART, those who achieved oIR had significantly higher E6-specific responses (9 of 34; 26.5%) compared with those with sIR (2 of 32; 6.3%) (P = 0.029). Apart from higher CD4 T-cell counts and lower CD4 T-cell activation, no other immunological correlates were associated with the detection of HPV16 and HPV52 E6-specific responses. HPV16 and HPV52 E6-specific IFN-γ T-cell responses, a correlate of protective immunity, were detected more frequently among HIV-infected patients who achieved optimal immune recovery on cART (26.5%) compared with those with suboptimal recovery (6.3%). © 2016 British HIV Association.

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.

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.

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.

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.

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

Trends in the clinical characteristics of HIV-infected patients initiating antiretroviral therapy in Kenya, Uganda and Tanzania between 2002 and 2009.

PubMed

Geng, Elvin H; Hunt, Peter W; Diero, Lameck O; Kimaiyo, Sylvester; Somi, Geofrey R; Okong, Pius; Bangsberg, David R; Bwana, Mwebesa B; Cohen, Craig R; Otieno, Juliana A; Wabwire, Deo; Elul, Batya; Nash, Denis; Easterbrook, Philippa J; Braitstein, Paula; Musick, Beverly S; Martin, Jeffrey N; Yiannoutsos, Constantin T; Wools-Kaloustian, Kara

2011-09-28

East Africa has experienced a rapid expansion in access to antiretroviral therapy (ART) for HIV-infected patients. Regionally representative socio-demographic, laboratory and clinical characteristics of patients accessing ART over time and across sites have not been well described. We conducted a cross-sectional analysis of characteristics of HIV-infected adults initiating ART between 2002 and 2009 in Kenya, Uganda and Tanzania and in the International Epidemiologic Databases to Evaluate AIDS Consortium. Characteristics associated with advanced disease (defined as either a CD4 cell count level of less than 50 cells/mm3 or a WHO Stage 4 condition) at the time of ART initiation and use of stavudine (D4T) or nevirapine (NVP) were identified using a log-link Poisson model with robust standard errors. Among 48,658 patients (69% from Kenya, 22% from Uganda and 9% from Tanzania) accessing ART at 30 clinic sites, the median age at the time of ART initiation was 37 years (IQR: 31-43) and 65% were women. Pre-therapy CD4 counts rose from 87 cells/mm3 (IQR: 26-161) in 2002-03 to 154 cells/mm3 (IQR: 71-233) in 2008-09 (p<0.001). Accessing ART at advanced disease peaked at 35% in 2005-06 and fell to 27% in 2008-09. D4T use in the initial regimen fell from a peak of 88% in 2004-05 to 59% in 2008-09, and a greater extent of decline was observed in Uganda than in Kenya and Tanzania. Self-pay for ART peaked at 18% in 2003, but fell to less than 1% by 2005. In multivariable analyses, accessing ART at advanced immunosuppression was associated with male sex, women without a history of treatment for prevention of mother to child transmission (both as compared with women with such a history) and younger age after adjusting for year of ART initiation and country of residence. Receipt of D4T in the initial regimen was associated with female sex, earlier year of ART initiation, higher WHO stage, and lower CD4 levels at ART initiation and the absence of co-prevalent tuberculosis. Public health ART services in east Africa have improved over time, but the fraction of patients accessing ART with advanced immunosuppression is still high, men consistently access ART with more advanced disease, and D4T continues to be common in most settings. Strategies to facilitate access to ART, overcome barriers among men and reduce D4T use are needed.

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

The plasma levels of soluble ST2 as a marker of gut mucosal damage in early HIV infection

PubMed Central

Mehraj, Vikram; Jenabian, Mohammad-Ali; Ponte, Rosalie; Lebouché, Bertrand; Costiniuk, Cecilia; Thomas, Réjean; Baril, Jean-Guy; LeBlanc, Roger; Cox, Joseph; Tremblay, Cécile; Routy, Jean-Pierre

2016-01-01

Objective: Following tissue barrier breaches, interleukin-33 (IL-33) is released as an ‘alarmin’ to induce inflammation. Soluble suppression of tumorigenicity 2 (sST2), as an IL-33 decoy receptor, contributes to limit inflammation. We assessed the relationship between the IL-33/ST2 axis and markers of gut mucosal damage in patients with early (EHI) and chronic HIV infection (CHI) and elite controllers. Design: Analyses on patients with EHI and CHI were conducted to determine IL-33/sST2 changes over time. Methods: IL-33 and sST2 levels were measured in plasma. Correlations between sST2 levels and plasma viral load, CD4+ and CD8+ T-cell counts, expression of T-cell activation/exhaustion markers, gut mucosal damage, microbial translocation and inflammation markers, as well as kynurenine/tryptophan ratio were assessed. Results: Plasma sST2 levels were elevated in EHI compared with untreated CHI and uninfected controls, whereas IL-33 levels were comparable in all groups. In EHI, sST2 levels were positively correlated with the CD8+ T-cell count and the percentage of T cells expressing activation and exhaustion markers, but not with viral load or CD4+ T-cell count. Plasma sST2 levels also correlated with plasma levels of gut mucosal damage, microbial translocation and kynurenine/tryptophan ratio and for some markers of inflammation. Prospective analyses showed that early antiretroviral therapy had no impact on sST2 levels, whereas longer treatment duration initiated during CHI normalized sST2. Conclusion: As sST2 levels were elevated in EHI and were correlated with CD8+ T-cell count, immune activation, and microbial translocation, sST2 may serve as a marker of disease progression, gut damage and may directly contribute to HIV pathogenesis. PMID:27045377

Fractional Brownian motion and multivariate-t models for longitudinal biomedical data, with application to CD4 counts in HIV-positive patients.

PubMed

Stirrup, Oliver T; Babiker, Abdel G; Carpenter, James R; Copas, Andrew J

2016-04-30

Longitudinal data are widely analysed using linear mixed models, with 'random slopes' models particularly common. However, when modelling, for example, longitudinal pre-treatment CD4 cell counts in HIV-positive patients, the incorporation of non-stationary stochastic processes such as Brownian motion has been shown to lead to a more biologically plausible model and a substantial improvement in model fit. In this article, we propose two further extensions. Firstly, we propose the addition of a fractional Brownian motion component, and secondly, we generalise the model to follow a multivariate-t distribution. These extensions are biologically plausible, and each demonstrated substantially improved fit on application to example data from the Concerted Action on SeroConversion to AIDS and Death in Europe study. We also propose novel procedures for residual diagnostic plots that allow such models to be assessed. Cohorts of patients were simulated from the previously reported and newly developed models in order to evaluate differences in predictions made for the timing of treatment initiation under different clinical management strategies. A further simulation study was performed to demonstrate the substantial biases in parameter estimates of the mean slope of CD4 decline with time that can occur when random slopes models are applied in the presence of censoring because of treatment initiation, with the degree of bias found to depend strongly on the treatment initiation rule applied. Our findings indicate that researchers should consider more complex and flexible models for the analysis of longitudinal biomarker data, particularly when there are substantial missing data, and that the parameter estimates from random slopes models must be interpreted with caution. © 2015 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

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.

Poor quality of life among untreated Thai and Cambodian children without severe HIV symptoms.

PubMed

Bunupuradah, Torsak; Puthanakit, Thanyawee; Kosalaraksa, Pope; Kerr, Stephen J; Kariminia, Azar; Hansudewechakul, Rawiwan; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Chuenyam, Theshinee; Vonthanak, Saphonn; Vun, Mean Chhi; Vibol, Ung; Vannary, Bun; Ruxrungtham, Kiat; Ananworanich, Jintanat

2012-01-01

There are limited data on quality of life (QOL) 1 in untreated HIV-infected children who do not have severe HIV symptoms. Moreover, such data do not exist for Asian children. Poor QOL could be a factor in deciding if antiretroviral therapy (ART) should be initiated. Thai and Cambodian children (n=294), aged 1-11 years, naïve to ART, with mild to moderate HIV symptoms and CD4 15-24% were enrolled. Their caregivers completed the Pediatric AIDS Clinical Trials Group QOL questionnaire prior to ART commencement. Six QOL domains were assessed using transformed scores that ranged from 0 to 100. Higher QOL scores indicated better health. Mean age was 6.1 (SD 2.8) years, mean CD4 was 723 (SD 369) cells/mm(3), 57% was female, and%CDC N:A:B was 2:63:35%. One-third knew their HIV diagnosis. Mean (SD) scores were 69.9 (17.6) for health perception, 64.5 (16.2) for physical resilience, 84.2 (15.6) for physical functioning, 77.9 (16.3) for psychosocial well-being, 74.7 (28.7) for social and role functioning, 90.0 (12.1) for health care utilization, and 87.4 (11.3) for symptoms domains. Children with CD4 counts above the 2008 World Health Organization (WHO) ART-initiation criteria (n=53) had higher scores in health perception and health care utilization than those with lower CD4 values. Younger children had poorer QOL than older children despite having similar mean CD4%. In conclusion, untreated Asian children without severe HIV symptoms had relatively low QOL scores compared to published reports in Western countries. Therapy initiation criteria by the WHO identified children with lower QOL scores to start ART; however, children who did not fit ART-initiation criteria and those who were younger also displayed poor QOL. QOL assessment should be considered in untreated children to inform decisions about when to initiate ART.

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.

Joint estimation of CD4+ cell progression and survival in untreated individuals with HIV-1 infection.

PubMed

Mangal, Tara D

2017-05-15

We compiled the largest dataset of seroconverter cohorts to date from 25 countries across Africa, North America, Europe, and Southeast/East (SE/E) Asia to simultaneously estimate transition rates between CD4 cell stages and death, in antiretroviral therapy (ART)-naive HIV-1-infected individuals. A hidden Markov model incorporating a misclassification matrix was used to represent natural short-term fluctuations and measurement errors in CD4 cell counts. Covariates were included to estimate the transition rates and survival probabilities for each subgroup. The median follow-up time for 16 373 eligible individuals was 4.1 years (interquartile range 1.7-7.1), and the mean age at seroconversion was 31.1 years (SD 8.8). A total of 14 525 individuals had recorded CD4 cell counts pre-ART, 1885 died, and 6947 initiated ART. Median (interquartile range) survival for men aged 20 years at seroconversion was 13.0 (12.4-13.4), 11.6 (10.9-12.3), and 8.3 years (7.9-8.9) in Europe/North America, Africa, and SE/E Asia, respectively. Mortality rates increase with age (hazard ratio 2.22, 95% confidence interval 1.84-2.67 for >45 years compared with <25 years) and vary by region (hazard ratio 2.68, 1.75-4.12 for Africa and 1.88, 1.50-2.35 for Asia compared with Europe/North America). CD4 cell decline was significantly faster in Asian cohorts compared with Europe/North America (hazard ratio 1.45, 1.36-1.54). Mortality and CD4 cell progression rates exhibited regional and age-specific differences, with decreased survival in African and SE/E Asian cohorts compared with Europe/North America and in older age groups. This extensive dataset reveals heterogeneities between regions and ages, which should be incorporated into future HIV models.

Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis.

PubMed

Weiss, M; Gross-Weege, W; Harms, B; Schneider, E M

1996-03-01

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.

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

The Immune Interaction between HIV-1 Infection and Mycobacterium tuberculosis.

PubMed

Du Bruyn, Elsa; Wilkinson, Robert John

2016-12-01

The modulation of tuberculosis (TB)-induced immunopathology caused by human immunodeficiency virus (HIV)-1 coinfection remains incompletely understood but underlies the change seen in the natural history, presentation, and prognosis of TB in such patients. The deleterious combination of these two pathogens has been dubbed a "deadly syndemic," with each favoring the replication of the other and thereby contributing to accelerated disease morbidity and mortality. HIV-1 is the best-recognized risk factor for the development of active TB and accounts for 13% of cases globally. The advent of combination antiretroviral therapy (ART) has considerably mitigated this risk. Rapid roll-out of ART globally and the recent recommendation by the World Health Organization (WHO) to initiate ART for everyone living with HIV at any CD4 cell count should lead to further reductions in HIV-1-associated TB incidence because susceptibility to TB is inversely proportional to CD4 count. However, it is important to note that even after successful ART, patients with HIV-1 are still at increased risk for TB. Indeed, in settings of high TB incidence, the occurrence of TB often remains the first presentation of, and thereby the entry into, HIV care. As advantageous as ART-induced immune recovery is, it may also give rise to immunopathology, especially in the lower-CD4-count strata in the form of the immune reconstitution inflammatory syndrome. TB-immune reconstitution inflammatory syndrome will continue to impact the HIV-TB syndemic.

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.

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

Uveitis as an initial manifestation of acquired immunodeficiency syndrome.

PubMed

Tsen, Chui-Lien; Chen, Shih-Chou; Chen, Yao-Shen; Sheu, Shwu-Jiuan

2017-10-01

Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) is a multisystem disease that can involve the human eyes. Using ophthalmic examination records from January 2006 to November 2015, we retrospectively reviewed all patients who were diagnosed with HIV/AIDS in our hospital. The study was performed at a tertiary referral center in southern Taiwan. Data included age, gender, ophthalmic examinations, systemic conditions, CD4 cell counts, course, and treatment. Eleven patients were identified as having AIDS with uveitis as their presenting manifestation. All were men, with a mean age of 39.5 ± 11.4 years (range 24-56). The mean CD4 + T-cell counts were 91.7 ± 50.3 cells/μl (range 27-169). Ocular diagnoses included cytomegalovirus (CMV) retinitis in five patients, ocular syphilis in four patients, and ocular toxoplasmosis in two patients. Uveitis resolved in all patients after medical treatment. However, a retinal detachment developed in two eyes in CMV retinitis and one eye in ocular syphilis. Ocular manifestations are among the most common clinical features in patients with HIV/AIDS who have varying clinical presentations that affect almost all ocular structures. This study demonstrated that ocular findings could be an initial manifestation of an underlying disease. Awareness of ocular lesions in HIV/AIDS is important for early recognition and management.

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.

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

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

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.

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

Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

PubMed Central

Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

2015-01-01

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109

High uptake of antiretroviral therapy among HIV-positive TB patients receiving co-located services in Swaziland.

PubMed

Pathmanathan, Ishani; Pasipamire, Munyaradzi; Pals, Sherri; Dokubo, E Kainne; Preko, Peter; Ao, Trong; Mazibuko, Sikhathele; Ongole, Janet; Dhlamini, Themba; Haumba, Samson

2018-01-01

Swaziland has the highest adult HIV prevalence and second highest rate of TB/HIV coinfection globally. Recently, the Ministry of Health and partners have increased integration and co-location of TB/HIV services, but the timing of antiretroviral therapy (ART) relative to TB treatment-a marker of program quality and predictor of outcomes-is unknown. We conducted a retrospective analysis of programmatic data from 11 purposefully-sampled facilities to evaluate timely ART provision for HIV-positive TB patients enrolled on TB treatment between July-November 2014. Timely ART was defined as within two weeks of TB treatment initiation for patients with CD4<50/μL or missing, and within eight weeks otherwise. Descriptive statistics were estimated and logistic regression used to assess factors independently associated with timely ART. Of 466 HIV-positive TB patients, 51.5% were male, median age was 35 (interquartile range [IQR]: 29-42), and median CD4 was 137/μL (IQR: 58-268). 189 (40.6%) were on ART prior to, and five (1.8%) did not receive ART within six months of TB treatment initiation. Median time to ART after TB treatment initiation was 15 days (IQR: 14-28). Almost 90% started ART within eight weeks, and 45.5% of those with CD4<50/μL started within two weeks. Using thresholds for "timely ART" according to baseline CD4 count, 73.3% of patients overall received timely ART after TB treatment initiation. Patients with CD4 50-200/μL or ≥200/μL had significantly higher odds of timely ART than patients with CD4<50/μL, with adjusted odds ratios of 11.5 (95% confidence interval [CI]: 5.0-26.6) and 9.6 (95% CI: 4.6-19.9), respectively. TB cure or treatment completion was achieved by 71.1% of patients at six months, but this was not associated with timely ART. This study demonstrates the relative success of integrated and co-located TB/HIV services in Swaziland, and shows that timely ART uptake for HIV-positive TB patients can be achieved in resource-limited, but integrated settings. Gaps remain in getting patients with CD4<50/μL to receive ART within the recommended two weeks post TB treatment initiation.

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.

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).

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.

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.

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.

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.

A combination SMS and transportation reimbursement intervention to improve HIV care following abnormal CD4 test results in rural Uganda: a prospective observational cohort study.

PubMed

Siedner, Mark J; Santorino, Data; Lankowski, Alexander J; Kanyesigye, Michael; Bwana, Mwebesa B; Haberer, Jessica E; Bangsberg, David R

2015-07-06

Up to 50 % of HIV-infected persons in sub-Saharan Africa are lost from care between HIV diagnosis and antiretroviral therapy (ART) initiation. Structural barriers, including cost of transportation to clinic and poor communication systems, are major contributors. We conducted a prospective, pragmatic, before-and-after clinical trial to evaluate a combination mobile health and transportation reimbursement intervention to improve care at a publicly operated HIV clinic in Uganda. Patients undergoing CD4 count testing were enrolled, and clinicians selected a result threshold that would prompt early return for ART initiation or further care. Participants enrolled in the pre-intervention period (January - August 2012) served as a control group. Participants in the intervention period (September 2012 - November 2013) were randomized to receive daily short message service (SMS) messages for up to seven days in one of three formats: 1) messages reporting an abnormal result directly, 2) personal identification number-protected messages reporting an abnormal result, or 3) messages reading "ABCDEFG" to confidentially convey an abnormal result. Participants returning within seven days of their first message received transportation reimbursements (about $6USD). Our primary outcomes of interest were time to return to clinic and time to ART initiation. There were 45 participants in the pre-intervention period and 138 participants in the intervention period (46, 49, and 43 in the direct, PIN, and coded groups, respectively) with low CD4 count results. Median time to clinic return was 33 days (IQR 11-49) in the pre-intervention period and 6 days (IQR 3-16) in the intervention period (P < 0.001); and median time to ART initiation was 47 days (IQR 11-75) versus 12 days (IQR 5-19), (P < 0.001). In multivariable models, participants in the intervention period had earlier return to clinic (AHR 2.32, 95 %CI 1.53 to 3.51) and earlier time to ART initiation (AHR 2.27, 95 %CI 1.38 to 3.72). All three randomized message formats improved time to return to clinic and time to ART initiation (P < 0.01 for all comparisons versus the pre-intervention period). A combination of an SMS laboratory result communication system and transportation reimbursements significantly decreased time to clinic return and time to ART initiation after abnormal CD4 test results. Clinicaltrials.gov NCT01579214 , approved 13 April 2012.

Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland.

PubMed

Bock, Naomi N; Emerson, Ruth C; Reed, Jason B; Nkambule, Rejoice; Donnell, Deborah J; Bicego, George T; Okello, Velephi; Philip, Neena M; Ehrenkranz, Peter D; Duong, Yen T; Moore, Janet S; Justman, Jessica E

2016-03-01

Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥ 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥ 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥ 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

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.

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.

Outcomes and factors associated with survival of patients with HIV/AIDS initiating antiretroviral treatment in Liangshan Prefecture, southwest of China

PubMed Central

Zhang, Guang; Gong, Yuhan; Wang, Qixing; Deng, Ling; Zhang, Shize; Liao, Qiang; Yu, Gang; Wang, Ke; Wang, Ju; Ye, Shaodong; Liu, Zhongfu

2016-01-01

Abstract Human immunodeficiency virus (HIV)–positive cases have been reported among people who injected drugs in Liangshan Prefecture in southwest of China since 1995 and Liangshan has become one of the most seriously affected epidemic areas in China. In 2004, several patients with HIV/acquired immunodeficiency syndrome (AIDS) initiated antiretroviral treatment (ART) at the Central Hospital of Liangshan Prefecture. From 2005 to 2013, the number of patients receiving ART dramatically increased. We conducted a retrospective cohort study to analyze the long-term survival time and associated factors among patients with HIV/AIDS who received ART in Liangshan Prefecture for the first time. Data were collected from the Chinese AIDS Antiretroviral Therapy DATAFax Information System. A life table and the Kaplan–Meier and Cox proportion hazard regression were used to calculate the survival time and its associated factors, respectively. Among 8310 ART-naïve patients with HIV/AIDS who initiated ART, 436 patients died of AIDS-related diseases, and their median time of receiving ART was 15.0 ± 12.3 months, whereas 28.7% of them died within the first 6 months after treatment. The cumulative survival rates of those receiving ART in 1, 2, 3, 4, and 5 years were 97.1%, 93.4%, 90.6%, 88.8%, and 86.0%, respectively. Multivariate Cox regression analysis showed that male patients on ART were at a higher risk of death from AIDS-related diseases (adjusted hazard ratio [AHR] = 1.5, 95% confidence interval [CI]: 1.1–2.1) than female patients. Patients infected with HIV through injection drug use (IDU) were at a higher risk of death (AHR = 1.6, 95% CI: 1.2–2.2) than those infected through heterosexual transmission. Patients with a baseline CD4 cell count <50/mm3 (AHR = 9.8, 95% CI: 6.0–15.9), 50–199/mm3 (AHR = 3.3, 95% CI: 2.3–4.6), and 200–349/mm3 (AHR = 1.7, 95% CI: 1.2–2.3) were at a higher risk of death than those with a CD4 cell count ≥350/mm3. ART prolonged survival time of patients with HIV/AIDS and improved their survival probability. Patients with HIV/AIDS should be consistently followed up and the CD4 T-cell count regularly monitored, and timely and early antiretroviral therapy initiated in order to achieve a better survival rate. PMID:27399071

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.

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

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.

Views of Medical Doctors Regarding the 2013 WHO Adult HIV Treatment Guidelines Indicate Variable Applicability for Routine Patient Monitoring, for Their Family Members and for Themselves, in South-Africa.

PubMed

Venter, Willem Daniel Francois; Fairlie, Lee; Feldman, Charles; Cleaton-Jones, Peter; Chersich, Matthew

2016-01-01

South African doctors (n = 211) experienced in antiretroviral therapy use were asked via an online questionnaire about the WHO 2013 adult antiretroviral integrated guidelines, as well as clinical and personal issues, in three hypothetical scenarios: directing the Minister of Health, advising a family member requiring therapy amidst unstable antiretroviral supplies, and where doctors themselves were HIV-positive. Doctors (54%) favoured the 500 cells/μl WHO initiation threshold if advising the Minister; a third recommended retaining the 350 cells/μl threshold used at the time of the survey. However, they favoured a higher initiation threshold for their family member. Doctors were 4.9 fold more likely to initiate modern treatment, irrespective of their CD4 cell count, for themselves than for public-sector patients (95%CI odds ratio = 3.33-7.33; P<0.001, although lower if limited to stavudine-containing regimens. Doctors were equally concerned about stavudine-induced lactic acidosis and lipoatrophy. The majority (84%) would use WHO-recommended first-line therapy, with concerns split between tenofovir-induced nephrotoxicity (55%), and efavirenz central nervous system effects (29%). A majority (61%), if HIV-positive, would pay for a pre-initiation resistance test, use influenza-prophylaxis (85%), but not INH-prophylaxis (61%), and treat their cholesterol and blood pressure concerns conventionally (63% and 60%). Over 60% wanted viral loads and creatinine measured six monthly. A third felt CD4 monitoring only necessary if clinically indicated or if virological failure occurred. They would use barrier prevention (83%), but not recommend pre-exposure prophylaxis, if their sexual partner was HIV-negative (68%). A minority would be completely open about their HIV status, but the majority would disclose to their sexual partners, close family and friends. Respondents were overwhelmingly in favour of continued antiretrovirals after breastfeeding. In conclusion, doctors largely supported adult WHO guidelines as public policy, although would initiate treatment at higher CD4 counts for their family and themselves. Resistance to INH-prophylaxis is unexpected and warrants investigation.

Mortality in the Year Following Antiretroviral Therapy Initiation in HIV-Infected Adults and Children in Uganda and Zimbabwe

PubMed Central

Walker, A. Sarah; Prendergast, Andrew J.; Mugyenyi, Peter; Munderi, Paula; Hakim, James; Kekitiinwa, Addy; Katabira, Elly; Gilks, Charles F.; Kityo, Cissy; Nahirya-Ntege, Patricia; Nathoo, Kusum; Gibb, Diana M.

2012-01-01

Background. Adult mortality in the first 3 months on antiretroviral therapy (ART) is higher in low-income than in high-income countries, with more similar mortality after 6 months. However, the specific patterns of changing risk and causes of death have rarely been investigated in adults, nor compared with children in low-income countries. Methods. We used flexible parametric hazard models to investigate how mortality risks varied over the first year on ART in human immunodeficiency virus–infected adults (aged 18–73 years) and children (aged 4 months to 15 years) in 2 trials in Zimbabwe and Uganda. Results. One hundred seventy-nine of 3316 (5.4%) adults and 39 of 1199 (3.3%) children died; half of adult/pediatric deaths occurred in the first 3 months. Mortality variation over year 1 was similar; at all CD4 counts/CD4%, mortality risk was greatest between days 30 and 50, declined rapidly to day 180, then declined more slowly. One-year mortality after initiating ART with 0–49, 50–99 or ≥100 CD4 cells/μL was 9.4%, 4.5%, and 2.9%, respectively, in adults, and 10.1%, 4.4%, and 1.3%, respectively, in children aged 4–15 years. Mortality in children aged 4 months to 3 years initiating ART in equivalent CD4% strata was also similar (0%–4%: 9.1%; 5%–9%: 4.5%; ≥10%: 2.8%). Only 10 of 179 (6%) adult deaths and 1 of 39 (3%) child deaths were probably medication-related. The most common cause of death was septicemia/meningitis in adults (20%, median 76 days) and children (36%, median 79 days); pneumonia also commonly caused child deaths (28%, median 41 days). Conclusions. Children ≥4 years and adults with low CD4 values have remarkably similar, and high, mortality risks in the first 3 months after ART initiation in low-income countries, similar to cohorts of untreated individuals. Bacterial infections are a major cause of death in both adults and children; targeted interventions could have important benefits. PMID:22972859

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.

Prevalence of Malnutrition and Associated Factors among Hospitalized Patients with Acquired Immunodeficiency Syndrome in Jimma University Specialized Hospital, Ethiopia.

PubMed

Mulu, Habtamu; Hamza, Leja; Alemseged, Fesehaye

2016-05-01

HIV/AIDS predisposes to malnutrition. Malnutrition exacerbates HIV/AIDS progression resulting in increased morbidity and mortality. The magnitude of malnutrition in HIV/AIDS patients has not been well studied in Ethiopian setup. Our objective was to assess the prevalence of malnutrition and associated factors among HIV/AIDS patients admitted to Jimma University Specialized Hospital (JUSH). A cross-sectional study was conducted to assess the nutritional status of 109 HIV/AIDS patients admitted from November 2013 to July 2014. Cohort design was also used for outcome assessment. Serum levels of hemoglobin, albumin and CD4 counts were determined. Data were organized, coded, cleaned, entered into a computer and analyzed using SPSS version 16.0. Descriptive analysis was done initially. Those variables in the bivariate analysis with P-value < 0.25 were then considered as candidates to be included in the multivariable logistic regression model. A P-vale of < 0.05 was considered as statistically significant. The mean age of the patients was 32.7±8.12 with male to female ratio of 1:1.9. Patients were in either clinical stage, 3(46.8%), or stage, 4(53.2%). Forty nine (45%) of the respondents had a CD4 count of < 200 cells/µL. The overall prevalence of malnutrition was 46.8% (BMI<18.5kg/m2) and 44.1% (MUAC≤ 20cm). Eighty four (77.1%) of the patients had a serum albumin level of ≤3.5g/dl while 76 (69.6%) of the patients had anemia (Hg<12g/dl). The prevalence of malnutrition was found to be high. WHO Stage 4 disease and CD4 count <200cells/µl were independent predictors of malnutrition.

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.

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.

Intestinal Parasitosis in Relation to CD4+T Cells Levels and Anemia among HAART Initiated and HAART Naive Pediatric HIV Patients in a Model ART Center in Addis Ababa, Ethiopia

PubMed Central

Mengist, Hylemariam Mihiretie; Taye, Bineyam; Tsegaye, Aster

2015-01-01

Background Intestinal parasites (IPs) are major concerns in most developing countries where HIV/AIDS cases are concentrated and almost 80% of AIDS patients die of AIDS-related infections. In the absence of highly active antiretroviral therapy (HAART), HIV/AIDS patients in developing countries unfortunately continue to suffer from the consequences of opportunistic and other intestinal parasites. The aim of the study was to determine the prevalence of intestinal parasites in relation to CD4+ T cells levels and anemia among HAART initiated and HAART naïve pediatric HIV patients in a Model ART center in Addis Ababa, Ethiopia. Methods A prospective comparative cross-sectional study was conducted among HAART initiated and HAART naive pediatric HIV/AIDS patients attending a model ART center at Zewditu Memorial Hospital between August 05, 2013 and November 25, 2013. A total of 180 (79 HAART initiated and 101 HAART naïve) children were included by using consecutive sampling. Stool specimen was collected and processed using direct wet mount, formol-ether concentration and modified Ziehl-Neelsen staining techniques. A structured questionnaire was used to collect data on socio-demographic and associated risk factors. CD4+ T cells and complete blood counts were performed using BD FACScalibur and Cell-Dyn 1800, respectively. The data was analyzed by SPSS version 16 software. Logistic regressions were applied to assess any association between explanatory factors and outcome variables. P values < 0.05 were taken as statistically significant. Results The overall prevalence of IPs was 37.8% where 27.8% of HAART initiated and 45.5% of HAART naive pediatric HIV/AIDS patients were infected (p < 0.05). Cryptosporidium species, E. histolytica/dispar, Hook worm and Taenia species were IPs associated with CD4+ T cell counts <350 cells/μμL in HAART naive patients. The overall prevalence of anemia was 10% in HAART and 31.7% in non-HAART groups. Hook worm, S. stercoralis and H. nana were helminthes significantly associated with anemia in non-HAART patients [AOR, 95% CI: 4.5(1.3, 15.2), P< 0.05]. The prevalence of IPs in non-HAART patients was significantly associated with eating unwashed/raw fruit [AOR, 95%CI: 6.3(1.2, 25.6), P<0.05], open field defecation [AOR, 95%CI: 9.3(1.6, 53.6), P<0.05] and diarrhea [AOR, 95%CI: 5.2(1.3, 21.3), P<0.05]. IPs significantly increased in rural residents [AOR, 95%CI: 0.4(0.1, 0.9, P<0.05)]. Conclusion The overall prevalence of intestinal parasites significantly differed by HAART status and cryptosporidium species were found only in HAART naïve patients with low CD4+ T cell counts. Anemia was also more prevalent and significantly associated with IPs in non-HAART patients. This study identified some environmental and associated risk factors for intestinal parasitic infections. Therefore, Public health measures should continue to emphasize the importance of environmental and personal hygiene to protect HIV/AIDS patients from infections with intestinal parasites and maximize the benefits of HAART. PMID:25658626

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.

T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years.

PubMed

Zijenah, Lynn S; Katzenstein, David A; Nathoo, Kusum J; Rusakaniko, Simbarashe; Tobaiwa, Ocean; Gwanzura, Christine; Bikoue, Arsene; Nhembe, Margaret; Matibe, Petronella; Janossy, George

2005-02-01

BACKGROUND: Serologic tests for HIV infection in infants less than 18 months do not differentiate exposure and infection since maternally acquired IgG antibodies may be detected in infants. Thus, the gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. There is an urgent need to evaluate alternative and cost effective laboratory methods for early diagnosis of infant HIV-1 infection as well as identifying infected infants who may benefit from cotrimoxazole prophylaxis and/or initiation of highly active antiretroviral therapy. METHODS: Whole blood was collected in EDTA from 137 infants aged 0 to 18 months. DNA polymerase chain reaction was used as the reference standard for diagnosis of HIV-1 infection. T-cell subset profiles were determined by flow cytometry. RESULTS: Seventy-six infants were DNA PCR positive while 61 were negative. The median CD4 counts of PCR negative infants were significantly higher than those of the PCR positive infants, p < 0.001. The median CD4/CD8 ratio and the %CD4 of the PCR positive infants were both significantly lower than those of the negative infants, p < 0.001. The CD4/CD8 ratio had a >98% sensitivity for diagnosis of HIV-1 infection and a specificity of >98%. CONCLUSION: The CD4/CD8 ratio appears useful in identifying HIV-infected infants. The development of lower cost and more robust flow cytometric methods that provide both CD4/CD8 ratio and %CD4 may be cost-effective for HIV-1 diagnosis and identification of infants for cotrimoxazole prophylaxis and/or highly active antiretroviral therapy.

T lymphocytes among HIV-infected and -uninfected infants: CD4/CD8 ratio as a potential tool in diagnosis of infection in infants under the age of 2 years

PubMed Central

Zijenah, Lynn S; Katzenstein, David A; Nathoo, Kusum J; Rusakaniko, Simbarashe; Tobaiwa, Ocean; Gwanzura, Christine; Bikoue, Arsene; Nhembe, Margaret; Matibe, Petronella; Janossy, George

2005-01-01

Background Serologic tests for HIV infection in infants less than 18 months do not differentiate exposure and infection since maternally acquired IgG antibodies may be detected in infants. Thus, the gold standard for diagnosis of HIV-1 infection in infants under the age of 2 years is DNA or reverse transcriptase polymerase chain reaction. There is an urgent need to evaluate alternative and cost effective laboratory methods for early diagnosis of infant HIV-1 infection as well as identifying infected infants who may benefit from cotrimoxazole prophylaxis and/or initiation of highly active antiretroviral therapy. Methods Whole blood was collected in EDTA from 137 infants aged 0 to 18 months. DNA polymerase chain reaction was used as the reference standard for diagnosis of HIV-1 infection. T-cell subset profiles were determined by flow cytometry. Results Seventy-six infants were DNA PCR positive while 61 were negative. The median CD4 counts of PCR negative infants were significantly higher than those of the PCR positive infants, p < 0.001. The median CD4/CD8 ratio and the %CD4 of the PCR positive infants were both significantly lower than those of the negative infants, p < 0.001. The CD4/CD8 ratio had a >98% sensitivity for diagnosis of HIV-1 infection and a specificity of >98%. Conclusion The CD4/CD8 ratio appears useful in identifying HIV-infected infants. The development of lower cost and more robust flow cytometric methods that provide both CD4/CD8 ratio and %CD4 may be cost-effective for HIV-1 diagnosis and identification of infants for cotrimoxazole prophylaxis and/or highly active antiretroviral therapy. PMID:15683549

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

Current scenario of opportunistic and co-infections in HIV-infected individuals at a tertiary care hospital in Mumbai, India.

PubMed

Chavan, V R; Chaudhary, V; Ahir, P; Mehta, R; Mavani, P S; Kerkar, C; Pramanik, J M

2015-01-01

An update on opportunistic infections/co-infections (OIs/CIs) is essential to understand the success of highly active antiretroviral therapy offered by the government agencies in reducing AIDS-related OIs/CIs. Hence, the present study aimed to evaluate the frequency of OIs/CIs in HIV-positive individuals at a tertiary care hospital in Mumbai. Its' association with CD4 counts, anti-retroviral treatment and on HIV transmission was also determined. An observational study was designed to evaluate different OIs/CIs in individuals, who tested positive for HIV infection at the ICTC/Shakti Clinic of Seth G.S. Medical College and KEM Hospital, Mumbai. Data analysis was done with the use of SPSS software (version 19.0, SPSS, Chicago, IL, USA). P value was considered significant if it is < 0.05. Heterosexual contact was the major route of transmission among the enrolled 185 individuals. Ninety (48.06%) HIV-infected individuals were with OIs/CIs. Tuberculosis (TB) was the most common OI (68.8%). Other CIs noted were Herpes zoster, syphilis, hepatitis C and B, malaria, typhoid and dengue. The median CD4 count in HIV-positive individuals with TB was 337 ± 248 cells/μl, and 67.7% of individuals with OIs/CIs had low CD4 counts (<400 cells/μl). Individuals in 31-40 years of age group had significantly (P = 0.01) more OIs/CIs. More (53.7%) spouse/children of HIV-positive individuals without OIs/CIs were HIV-1 positive. Low proportions of individuals with or without OIs/CIs were on ART. Nearly half of HIV-infected individuals were with OIs/CIs. Initiation of free ART programme since 2004 possibly associated with the type and rate of OIs/CIs. Tuberculosis and multiple OIs/CIs were associated with low CD4 counts. Infection was high in 31-40 years age group. Most of the spouses of individuals without OIs/CIs were HIV positive, indirectly indicates lack of condom use or lack of awareness of condom use.

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.

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.

Enhancement of Spirulina biomass production and cadmium biosorption using combined static magnetic field.

PubMed

Shao, Weilan; Ebaid, Reham; Abomohra, Abd El-Fatah; Shahen, Mohamed

2018-06-06

The effect of static magnetic field (SMF) on Spirulina platensis growth and its influence on cadmium ions (Cd 2+ ) removal efficiency were studied. Application of 6 h day -1 SMF resulted in the highest significant biomass productivity of 0.198 g L -1  day -1 . However, 10 and 15 mg L -1 of Cd 2+ resulted in significant reduction in biomass productivity by 8.8 and 12.5%, respectively, below the control. Combined SMF showed 30.1% significant increase in biomass productivity over the control. On the other hand, increase of initial Cd 2+ concentration resulted in significant reduction of Cd 2+ removal efficiency, representing 79.7% and 61.5% at 10 and 15 mg L -1 , respectively, after 16 days. Interestingly, application of SMF for 6 h day -1 enhanced Cd 2+ removal efficiency counted by 91.4% and 82.3% after 20 days for cultures with initial Cd 2+ concentration of 10 and 15 mg L -1 , representing increase by 6.3 and 25.3%, respectively, over the SMF-untreated cultures. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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.

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.

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.

Use of first line antiretroviral therapy from a free ART programme clinic in Pune, India - a preliminary report.

PubMed

Ghate, Manisha; Tripathy, Srikanth; Gangakhedkar, Raman; Thakar, Madhuri; Bhattacharya, Jayanta; Choudhury, Ipsita; Risbud, Arun; Bembalkar, Shilpa; Kadam, Dileep; Rewari, Bharat B; Paranjape, Ramesh

2013-05-01

The treatment outcomes under national antiretroviral therapy (ART) programme are being evaluated in some ART centres in the country. We carried out this study to analyze the impact of first line antiretroviral therapy in HIV infected patients attending a free ART roll out national programme clinic in Pune, India. Antiretroviral naive HIV infected patients attending the clinic between December 2005 and April 2008 and followed up till March 31, 2011 were included in the analysis. The enrolment and follow up of these patients were done as per the national guidelines. Viral load estimations were done in a subset of patients. results: One hundred and forty two patients with median CD4 count of 109 cells/μl (IQR: 60-160) were initiated on treatment. The median follow up was 44 months (IQR: 37-53.3 months). Survival analysis showed that the probability of being alive at the end of 5 years was 85 per cent. Overall increase in the median CD4 count was statistically significant (P<0.001). It was significant in patients with >95 per cent adherence (P<0.001). In 14 per cent patients, the absolute CD4 count did not increase by 100 or more cells/μl at the end of 12 months. Viral load estimation in a subset of 68 patients showed undetectable levels in 61 (89.7%) patients after a median duration of 46 months (IQR: 38.3-54.8). The first line treatment was effective in patients attending the programme clinic. The adherence level influenced immunological and virological outcomes of patients.

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

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.

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

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.

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.

Factors affecting the CD34+ cell yields from the second donations of healthy donors: The steady-state lymphocyte count is a good predictive factor.

PubMed

Guo, Zhi-Ping; Wang, Tao; Xu, Lan-Ping; Zhang, Xiao-Hui; Wang, Yu; Huang, Xiao-Jun; Chang, Ying-Jun

2016-12-01

A second allogeneic hematopoietic stem-cell transplantation and donor lymphocyte infusion using cells from the same donor is a therapeutic option in the case of stem-cell graft failure or disease relapse, but little is known about the factors associated with the CD34 + cell yields from second donations. One-hundred healthy donors who underwent a second mobilization treatment and peripheral blood stem-cell (PBSC) collection were studied. For both mobilization processes, 5 µg of granulocyte colony-stimulating factor per kg per day was administered. The blood counts of the donors were monitored during the processes. The second donations from the same donors provided lower apheresis yields than did the initial collections. The number of CD34 + cells collected from normal donors after a second cycle of PBSC mobilization was associated with their steady-state lymphocyte counts and the intertransplantation interval. Female sex negatively affected the CD34 + cell yields. The cutoff value for the steady-state absolute lymphocyte count was 2.055 × 10 9 /L. To harvest greater numbers of CD34 + cells from second collections, male donors and those with intervals of longer than 9 months between donations should be selected. The lymphocyte counts prior to the first donations may predict the content of CD34 + cells in the allografts prepared using the second donations. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Evaluation of peripheral blood T lymphocyte surface activation markers and transcription factors in patients with early stage non-small cell lung cancer.

PubMed

Rutkowski, Jacek; Cyman, Marta; Ślebioda, Tomasz; Bemben, Kamila; Rutkowska, Aleksandra; Gruchała, Marcin; Kmieć, Zbigniew; Pliszka, Agnieszka; Zaucha, Renata

2017-12-01

Lung cancer cells harboring multiple mutations as a consequence of long-term damage by different etiologic factors are responsible for high immunogenicity. Immune checkpoint inhibitors significantly improve treatment results in non-small cell lung cancer (NSCLC). Unfortunately, the role of T-lymphocytes in early NSCLC has not been sufficiently elucidated. The aim of this study was to characterize peripheral blood T cells expressing several selected surface antigens (CD4, CD8, CD25, CD28, PD-1, CTLA-4) and transcription factors (T-bet, ROR-yt, Fox-P3, GATA-3) in this patient population. The study group (LC) consisted of 80 treatment-naïve patients with T1/2aN0M0 NSCLC and was compared with 40 cancer-free patients matched for non-oncological diseases and demographic parameters (CG). Significantly higher counts of CTLA-4+cells (in both CD4+and CD8+subtypes), a lower proportion of PD-1 expressing cells and a significantly higher percentage of Fox-P3+CD4+cells were found in the LC group. The high proportion of CD4+PD-1+cells significantly correlated with poor outcomes in LC group, while low CD4/CD8 ratio predicted a better prognosis. Based on our results it seems that NSCLC even at early stages of development initiate changes in the proportions of T cells that may have a significant impact on the clinical outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

Economic and epidemiological impact of early antiretroviral therapy initiation in India

PubMed Central

Maddali, Manoj V; Dowdy, David W; Gupta, Amita; Shah, Maunank

2015-01-01

Introduction Recent WHO guidance advocates for early antiretroviral therapy (ART) initiation at higher CD4 counts to improve survival and reduce HIV transmission. We sought to quantify how the cost-effectiveness and epidemiological impact of early ART strategies in India are affected by attrition throughout the HIV care continuum. Methods We constructed a dynamic compartmental model replicating HIV transmission, disease progression and health system engagement among Indian adults. Our model of the Indian HIV epidemic compared implementation of early ART initiation (i.e. initiation above CD4 ≥350 cells/mm3) with delayed initiation at CD4 ≤350 cells/mm3; primary outcomes were incident cases, deaths, quality-adjusted-life-years (QALYs) and costs over 20 years. We assessed how costs and effects of early ART initiation were impacted by suboptimal engagement at each stage in the HIV care continuum. Results Assuming “idealistic” engagement in HIV care, early ART initiation is highly cost-effective ($442/QALY-gained) compared to delayed initiation at CD4 ≤350 cells/mm3 and could reduce new HIV infections to <15,000 per year within 20 years. However, when accounting for realistic gaps in care, early ART initiation loses nearly half of potential epidemiological benefits and is less cost-effective ($530/QALY-gained). We project 1,285,000 new HIV infections and 973,000 AIDS-related deaths with deferred ART initiation with current levels of care-engagement in India. Early ART initiation in this continuum resulted in 1,050,000 new HIV infections and 883,000 AIDS-related deaths, or 18% and 9% reductions (respectively), compared to current guidelines. Strengthening HIV screening increases benefits of earlier treatment modestly (1,001,000 new infections; 22% reduction), while improving retention in care has a larger modulatory impact (676,000 new infections; 47% reduction). Conclusions Early ART initiation is highly cost-effective in India but only has modest epidemiological benefits at current levels of care-engagement. Improved retention in care is needed to realize the full potential of earlier treatment. PMID:26434780

Clinical, Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe

PubMed Central

Makadzange, A. T.; Higgins-Biddle, M.; Chimukangara, B.; Birri, R.; Gordon, M.; Mahlanza, T.; McHugh, G.; van Dijk, J. H.; Bwakura-Dangarembizi, M.; Ndung’u, T.; Masimirembwa, C.; Phelps, B.; Amzel, A.; Ojikutu, B. O.; Walker, B. D.; Ndhlovu, C. E.

2015-01-01

Objective To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country. Methods A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10–19 years) attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record. Results Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001). The median age at ART initiation was 8.0 years (IQR 3.0, 12.0); median time on ART was 2.9 years (IQR 1.7, 4.5). On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years) at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001). Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180). Children (<10y) on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239). In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324), and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379) were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates. Conclusions During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes. PMID:26658814

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study

PubMed Central

Caniglia, Ellen C.; Sabin, Caroline; Robins, James M.; Logan, Roger; Cain, Lauren E.; Abgrall, Sophie; Mugavero, Michael J.; Hernandez-Diaz, Sonia; Meyer, Laurence; Seng, Remonie; Drozd, Daniel R.; Seage, George R.; Bonnet, Fabrice; Dabis, Francois; Moore, Richard R.; Reiss, Peter; van Sighem, Ard; Mathews, William C.; del Amo, Julia; Moreno, Santiago; Deeks, Steven G.; Muga, Roberto; Boswell, Stephen L.; Ferrer, Elena; Eron, Joseph J.; Napravnik, Sonia; Jose, Sophie; Phillips, Andrew; Olson, Ashley; Justice, Amy C.; Tate, Janet P.; Bucher, Heiner C.; Egger, Matthias; Touloumi, Giota; Sterne, Jonathan A.; Costagliola, Dominique; Saag, Michael; Hernán, Miguel A.

2016-01-01

Objective: To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). Design: Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. Methods: Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9–12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. Results: In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9–12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were −5.3 (−18.6 to 7.9) and −31.7 (−52.0 to −11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. Conclusions: Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question. PMID:26895294

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.

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.

Risk factors for Clostridium difficile infection in HIV-infected patients.

PubMed

Imlay, Hannah; Kaul, Daniel; Rao, Krishna

2016-01-01

Clostridium difficile infection is a healthcare-associated infection resulting in significant morbidity. Although immunosuppression is associated with Clostridium difficile infection acquisition and adverse outcomes, the epidemiology of Clostridium difficile infection in HIV-infected patients has been little studied in the era of antiretroviral therapy. This study identifies the risk factors for acquisition of Clostridium difficile infection in HIV-infected patients. A retrospective, propensity score-matched case-control study design was employed, with patients selected from our institution's outpatient HIV clinic. Clostridium difficile infection cases were defined as having positive stool testing plus an appropriate clinical presentation. The propensity score was generated via multiple logistic regression from year of HIV diagnosis, age at first contact, duration of follow-up, gender, and initial CD4 count. The 46 cases included were matched to a total of 180 controls. Prior antibiotic treatment was a significant predictor of Clostridium difficile infection (odds ratio: 13, 95% confidence interval: 3.49-48.8, p  < .001) as was number of hospital admissions in the preceding year (odds ratio: 4.02, confidence interval: 1.81-8.94, p  < .001). Having both proton pump inhibitor use and CD4 count <200 cells/µL significantly increased odds of Clostridium difficile infection in the multivariable model (odds ratio: 15.17, confidence interval: 1.31-175.9, p  = .021). As in the general population, frequent hospitalizations and exposure to antimicrobials are independent predictors of Clostridium difficile infection acquisition in patients with HIV. Additionally, low CD4 count and proton pump inhibitor use are new potentially modifiable variables that can be targeted for prevention of Clostridium difficile infection in future interventional studies.

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.

Efficacy and Safety of Lopinavir/ritonavir- versus Efavirenz-based Antiretroviral Therapy in HIV-Infected Pregnant Ugandan Women

PubMed Central

COHAN, Deborah; NATUREEBA, Paul; KOSS, Catherine A.; PLENTY, Albert; LUWEDDE, Flavia; MWESIGWA, Julia; ADES, Veronica; CHARLEBOIS, Edwin D.; GANDHI, Monica; CLARK, Tamara D.; NZARUBARA, Bridget; ACHAN, Jane; RUEL, Theodore; KAMYA, Moses R.; HAVLIR, Diane V.

2015-01-01

Objective Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4 cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda. Design Randomized clinical trial. Methods We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir- versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naïve pregnant women at 12–28 weeks gestation and any CD4 cell count were randomized. ART was provided and participants were counseled to breastfeed for one year postpartum. Results The median age of the 389 study participants was 29 years; median CD4 cell count was 370 cells/mm3. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm, p <0.001. At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression, p = 0.49. Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm) and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz), p = 0.10. Conclusions Virologic suppression at delivery was higher with an efavirenz- versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through one year postpartum and the risk of transmission to infants was low. PMID:25426808

Efficacy and safety of lopinavir/ritonavir versus efavirenz-based antiretroviral therapy in HIV-infected pregnant Ugandan women.

PubMed

Cohan, Deborah; Natureeba, Paul; Koss, Catherine A; Plenty, Albert; Luwedde, Flavia; Mwesigwa, Julia; Ades, Veronica; Charlebois, Edwin D; Gandhi, Monica; Clark, Tamara D; Nzarubara, Bridget; Achan, Jane; Ruel, Theodore; Kamya, Moses R; Havlir, Diane V

2015-01-14

Combination antiretroviral therapy (ART) is now the global standard for HIV-infected pregnant and breastfeeding women at all CD4⁺ cell counts. We compared the efficacy and safety of an efavirenz versus lopinavir/ritonavir regimen for HIV-infected pregnant women initiating ART in rural Uganda. Randomized clinical trial. We performed a planned secondary analysis comparing viral load suppression (HIV-1 RNA ≤400 copies/ml), safety, and HIV transmission to infants in a trial designed to test the hypothesis that lopinavir/ritonavir versus efavirenz-based ART would reduce placental malaria (PROMOTE, ClinicalTrials.gov, NCT00993031). HIV-infected, ART-naive pregnant women at 12-28 weeks gestation and any CD4⁺ cell count were randomized. ART was provided and participants were counseled to breastfeed for 1 year postpartum. The median age of the 389 study participants was 29 years; median CD4⁺ cell count was 370 cells/μl. At delivery, virologic suppression was 97.6% in the efavirenz arm and 86.0% in the lopinavir/ritonavir arm (P < 0.001). At 48 weeks postpartum, 91.0% of women on efavirenz and 88.4% on lopinavir/ritonavir had viral suppression (P = 0.49). Grade 1 or 2 gastrointestinal adverse events were higher among women on lopinavir/ritonavir versus efavirenz. Only two infants acquired HIV (both in the lopinavir/ritonavir arm), and HIV-free infant survival was similar between study arms: 92.9% (lopinavir/ritonavir) versus 97.2% (efavirenz) (P = 0.10). Virologic suppression at delivery was higher with an efavirenz versus lopinavir/ritonavir-based regimen. However, women in both arms achieved high levels of virologic suppression through 1 year postpartum and the risk of transmission to infants was low.

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.

Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women

PubMed Central

Onoya, Dorina; Sineke, Tembeka; Brennan, Alana T.; Long, Lawrence; Fox, Matthew P.

2017-01-01

Objectives: We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. Design: This is a retrospective cohort study of 6306 HIV-positive women aged 15–49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. Methods: The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. Results: The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1–2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4+ cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1–3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4+ cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7–1.1) and those who initiated ART in pregnancy. Conclusion: The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART. PMID:28463877

Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women.

PubMed

Onoya, Dorina; Sineke, Tembeka; Brennan, Alana T; Long, Lawrence; Fox, Matthew P

2017-07-17

We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. This is a retrospective cohort study of 6306 HIV-positive women aged 15-49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1-2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4 cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1-3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4 cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7-1.1) and those who initiated ART in pregnancy. The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART.

Immunopathology of immune reconstitution inflammatory syndrome in Whipple's disease.

PubMed

Moos, Verena; Feurle, Gerhard E; Schinnerling, Katina; Geelhaar, Anika; Friebel, Julian; Allers, Kristina; Moter, Annette; Kikhney, Judith; Loddenkemper, Christoph; Kühl, Anja A; Erben, Ulrike; Fenollar, Florence; Raoult, Didier; Schneider, Thomas

2013-03-01

During antimicrobial treatment of classic Whipple's disease (CWD), the chronic systemic infection with Tropheryma whipplei, immune reconstitution inflammatory syndrome (IRIS), is a serious complication. The aim of our study was to characterize the immunological processes underlying IRIS in CWD. Following the definition of IRIS, we describe histological features of IRIS and immunological parameters of 24 CWD IRIS patients, 189 CWD patients without IRIS, and 89 healthy individuals. T cell reconstitution, Th1 reactivity, and the phenotype of T cells were described in the peripheral blood, and infiltration of CD4(+) T cells and regulatory T cells in the duodenal mucosa was determined. During IRIS, tissues were heavily infiltrated by CD3(+), predominantly CD45RO(+)CD4(+) T cells. In the periphery, initial reduction of CD4(+) cell counts and their reconstitution on treatment was more pronounced in CWD patients with IRIS than in those without IRIS. The ratio of activated and regulatory CD4(+) T cells, nonspecific Th1 reactivity, and the proportion of naive among CD4(+) T cells was high, whereas serum IL-10 was low during IRIS. T. whipplei-specific Th1 reactivity remained suppressed before and after emergence of IRIS. The findings that IRIS in CWD mainly are mediated by nonspecific activation of CD4(+) T cells and that it is not sufficiently counterbalanced by regulatory T cells indicate that flare-up of pathogen-specific immunoreactivity is not instrumental in the pathogenesis of IRIS in CWD.

Modeling the impact of early antiretroviral therapy for adults coinfected with HIV and hepatitis B or C in South Africa.

PubMed

Martin, Natasha K; Devine, Angela; Eaton, Jeffrey W; Miners, Alec; Hallett, Timothy B; Foster, Graham R; Dore, Gregory J; Easterbrook, Philippa J; Legood, Rosa; Vickerman, Peter

2014-01-01

There has been discussion about whether individuals coinfected with HIV and hepatitis C virus (HCV) or hepatitis B virus (HBV) (∼30% of all people living with HIV) should be prioritized for early HIV antiretroviral therapy (ART). We assess the relative benefits of providing ART at CD4 count below 500  cells/μl or immediate ART to HCV/HIV or HBV/HIV-coinfected adults compared with HIV-monoinfected adults. We evaluate individual outcomes (HIV/liver disease progression) and preventive benefits in a generalized HIV epidemic setting. We modeled disease progression for HIV-monoinfected, HBV/HIV-coinfected, and HCV/HIV-coinfected adults for differing ART eligibility thresholds (CD4 <350  cells/μl, CD4 <500  cells/μl, immediate ART eligibility upon infection). We report disability-adjusted life-years averted per 100 person-years on ART (DALYaverted/100PYonART) as a measure of the health benefits generated from incremental changes in ART eligibility. Sensitivity analyses explored impact on sexual HIV and vertical HIV, HCV, and HBV transmission. For HBV/HIV-coinfected adults, a switch to ART initiation at CD4 count below 500  cells/μl from CD4 below 350  cells/μl generates 9% greater health benefits per year on ART (48 DALYaverted/100PYonART) than for HIV-monoinfected adults (44 DALYaverted/100PYonART). Additionally, ART at CD4 below 500  cells/μl could prevent 25% and 32% of vertical transmissions of HIV and HBV, respectively. For HCV/HIV-coinfected adults, ART at CD4 below 500  cells/μl generates 10% fewer health benefits (40 DALYaverted/100PYonART) than for HIV monoinfection, unless ART reduces progression to cirrhosis by more than 70% (33% in base-case). The additional therapeutic benefits of ART for HBV-related liver disease results in ART generating more health benefits among HBV/HIV-coinfected adults than HIV-monoinfected individuals, whereas less health benefits are generated amongst HCV/HIV coinfection in a generalized HIV epidemic setting.

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

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).

Safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus: Results from a phase 1/2 randomized study.

PubMed

Tsuru, Tomomi; Tanaka, Yoshiya; Kishimoto, Mitsumasa; Saito, Kazuyoshi; Yoshizawa, Seiji; Takasaki, Yoshinari; Miyamura, Tomoya; Niiro, Hiroaki; Morimoto, Shinji; Yamamoto, Junichi; Lledo-Garcia, Rocio; Shao, Jing; Tatematsu, Shuichiro; Togo, Osamu; Koike, Takao

2016-01-01

This 12-week, randomized, double-blind, placebo-controlled, multicenter phase 1/2 study (NCT01449071) assessed the safety, pharmacokinetics, and pharmacodynamics of epratuzumab in Japanese patients with moderate-to-severe systemic lupus erythematosus despite standard of care. Twenty patients were randomized 1:1:1:1:1 to placebo or one of four epratuzumab dose regimens (100 mg every other week [Q2W], 400 mg Q2W, 600 mg every week [QW], or 1200 mg Q2W) administered during an initial 4-week dosing period. Adverse events (AEs), pharmacokinetics and pharmacodynamics were assessed. Nineteen of 20 patients completed the study. All placebo patients and 13 of 16 epratuzumab patients reported ≥1 AE, 2 of 16 epratuzumab patients reported a serious AE. C(max) and AUC(τ) increased proportionally with dose after first and last infusion, t(1/2) was similar across groups (∼13 days). Epratuzumab treatment was associated with decreased CD22 mean fluorescence intensity in total B cells (CD19(+)CD22(+)) and unswitched memory B cells (CD19(+)IgD(+)CD27(+)). Small-to-moderate decreases were observed in total B cell (CD20(+)) count. Epratuzumab was well-tolerated, with no new safety signals identified. The pharmacokinetics appeared linear after first and last infusions. Treatment with epratuzumab was associated with CD22 downregulation and with small-to-moderate decreases in total B cell count.

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

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.

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.

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.

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

Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana.

PubMed

Zash, Rebecca; Souda, Sajini; Chen, Jennifer Y; Binda, Kelebogile; Dryden-Peterson, Scott; Lockman, Shahin; Mmalane, Mompati; Makhema, Joseph; Essex, Max; Shapiro, Roger

2016-04-01

Before introduction of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), 3-drug antiretroviral therapy (ART) was associated with increased adverse birth outcomes when used for prevention of mother-to-child HIV transmission (PMTCT) in Botswana. We extracted obstetric records from all women at the 2 largest maternities in Botswana from 2009-2011 when Botswana National Guidelines recommended zidovudine (ZDV) from 28 weeks gestational age (GA) for CD4 ≥350 and ART for CD4 <350, and again in 2013-2014 after implementation of TDF/FTC/EFV for prevention of mother-to-child HIV transmission regardless of CD4 or GA. We compared the use of TDF/FTC/EFV in pregnancy with other 3-drug ART regimens, and with initiation of ZDV, among women with similar CD4 cell counts. Outcomes included small for gestational age (SGA), preterm delivery (PTD) (<37 weeks GA), and stillbirths (SB). Among 9445 HIV-infected women delivering during the study period, 170 were on TDF/FTC/EFV at conception and 1468 initiated TDF/FTC/EFV during pregnancy. Adverse birth outcomes were high overall (3% SB, 21% PTD, and 18% SGA) and among women receiving TDF/FTC/EFV (3% SB, 22% PTD, and 12% SGA). There was no difference in PTD or SB among women initiating TDF/FTC/EFV compared with ZDV or other 3-drug ART, but initiating TDF/FTC/EFV was associated with fewer SGA infants than other 3-drug ART (adjusted odds ratio: 0.4, 95% confidence interval: 0.2 to 0.7). Adverse birth outcomes remain high among HIV-infected women. TDF/FTC/EFV was at least as safe as other ART and associated with fewer SGA infants when initiated during pregnancy. Larger studies are needed to evaluate birth outcomes and congenital abnormalities among women on TDF/FTC/EFV at conception.

Diagnostic accuracy of a point-of-care urine test for tuberculosis screening among newly-diagnosed HIV-infected adults: a prospective, clinic-based study.

PubMed

Drain, Paul K; Losina, Elena; Coleman, Sharon M; Giddy, Janet; Ross, Douglas; Katz, Jeffrey N; Walensky, Rochelle P; Freedberg, Kenneth A; Bassett, Ingrid V

2014-02-26

A rapid diagnostic test for active tuberculosis (TB) at the clinical point-of-care could expedite case detection and accelerate TB treatment initiation. We assessed the diagnostic accuracy of a rapid urine lipoarabinomannan (LAM) test for TB screening among HIV-infected adults in a TB-endemic setting. We prospectively enrolled newly-diagnosed HIV-infected adults (≥18 years) at 4 outpatient clinics in Durban from Oct 2011-May 2012, excluding those on TB therapy. A physician evaluated all participants and offered CD4 cell count testing. Trained study nurses collected a sputum sample for acid-fast bacilli smear microscopy (AFB) and mycobacterial culture, and performed urine LAM testing using Determine™ TB LAM in the clinic. The presence of a band regardless of intensity on the urine LAM test was considered positive. We defined as the gold standard for active pulmonary TB a positive sputum culture for Mycobacterium tuberculosis. Diagnostic accuracy of urine LAM was assessed, alone and in combination with smear microscopy, and stratified by CD4 cell count. Among 342 newly-diagnosed HIV-infected participants, 190 (56%) were male, mean age was 35.6 years, and median CD4 was 182/mm3. Sixty participants had culture-positive pulmonary TB, resulting in an estimated prevalence of 17.5% (95% CI 13.7-22.0%). Forty-five (13.2%) participants were urine LAM positive. Mean time from urine specimen collection to LAM test result was 40 minutes (95% CI 34-46 minutes). Urine LAM test sensitivity was 28.3% (95% CI 17.5-41.4) overall, and 37.5% (95% CI 21.1-56.3) for those with CD4 count <100/mm3, while specificity was 90.1% (95% CI 86.0-93.3) overall, and 86.9% (95% CI 75.8-94.2) for those with CD4 < 100/mm3. When combined with sputum AFB (either test positive), sensitivity increased to 38.3% (95% CI 26.0-51.8), but specificity decreased to 85.8% (95% CI 81.1-89.7). In this prospective, clinic-based study with trained nurses, a rapid urine LAM test had low sensitivity for TB screening among newly-diagnosed HIV-infected adults, but improved sensitivity when combined with sputum smear microscopy.

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.

[Efficacy of antiretroviral therapy and influencing factors for people living with HIV/AIDS in designated hospitals in Harbin].

PubMed

Zhao, P Y; Yu, X; Yang, K; Feng, S Y; Wang, F X; Wang, B Y

2016-05-01

To understand the efficacy of antiretroviral therapy for people living with HIV/AIDS and influencing factors; and provide evidence to improve the treatment of HIV infection and AIDS for the better life of the patients. A cross sectional study was conducted in designated AIDS hospitals in Harbin. A questionnaire was used to collect the information of the patients receiving treatment in these hospitals. The statistical analysis was done with software SAS 9.2 and Excel 2010. Univariate analysis was performed with t test and multivariate analysis was performed with ordinal logistic regression model. Wilcoxon ranks sum test was conducted to compare the CD4(+) T lymphocyte counts. The number of the patients receiving antiretroviral therapy was in increase in recent years. The HIV infection route was mainly homosexual contact. The CD4(+)T lymphocyte count of the patients increased at different levels after ≥6 months treatment(P<0.01). Household income(P<0.05), adherence to treatment plan or not(P<0.05), social relationship(P< 0.05), concern of economic cost(P<0.01)medication compliance(P<0.01)and initial level of CD4(+) T lymphocyte(P<0.01)were the influencing factors for antiretroviral therapy efficacy. In designated hospitals in Harbin, the number of the patients receiving HIV antiretroviral therapy kept to increase and the efficacy of the treatment was obvious.

Impact of medical and nonmedical factors on physician decision making for HIV/AIDS antiretroviral treatment.

PubMed

Bogart, L M; Kelly, J A; Catz, S L; Sosman, J M

2000-04-15

To examine influences of medical factors (e.g., viral load) and nonmedical factors (e.g., patient characteristics) on treatment decisions for highly active antiretroviral therapy (HAART), we sent a survey to a random sample of 995 infectious disease physicians who treat patients with HIV/AIDS in the United States in August, 1998. The response rate was 53%. Respondents were asked to report their current practices with respect to antiretroviral treatment and the extent to which each of three medical and 17 nonmedical factors would influence them for or against prescribing HAART to a hypothetical HIV-positive patient. Most reported initiating HAART with findings of low CD4+ cell counts and high viral loads, and weighing CD4+ cell counts, viral load, and opportunistic infection heavily in their decisions to prescribe HAART. Patients' prior history of poor adherence was weighed very much against initiating HAART. Patient homelessness, heavy alcohol use, injection drug use, and prior psychiatric hospitalization were cited by most physicians as weighing against HAART initiation. Thus, most physicians in this sample follow guidelines for the use of HAART, and nonmedical factors related to patients' life situations are weighed as heavily as disease severity in treatment decisions. As HIV increasingly becomes a disease associated with economic disadvantage and other social health problems, it will be essential to develop interventions and care support systems to enable patients experiencing these problems to benefit from HIV treatment advances.

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.

Incidence and risk factors for immune reconstitution inflammatory syndrome in an ethnically diverse HIV type 1-infected cohort.

PubMed

Ratnam, I; Chiu, C; Kandala, N-B; Easterbrook, P J

2006-02-01

It is estimated that 10%-25% of patients who start highly active antiretroviral therapy (HAART) experience immune reconstitution inflammatory syndrome (IRIS). Our objective was to determine the incidence, clinical spectrum, and predictors of IRIS in an ethnically diverse cohort of patients initiating HAART. A retrospective study of all patients starting HAART between 1 January 2000 and 31 August 2002 at a human immunodeficiency virus (HIV) clinic in London was performed. All laboratory measurements and data on antiretroviral therapies were obtained from the clinic database. Medical records were reviewed to identify clinical events consistent with IRIS during the 6 months after HAART was initiated. A total of 199 patients were included, of whom 50.8% were male, 59.3% were black African, 29.1% were white, and 10.5% were black Caribbean. The median baseline CD4 cell count and HIV RNA load were 174x10(6) cells/L (interquartile range [IQR], 82-285x10(6) cells/L) and 37,830 copies/mL (IQR, 4809-149,653 copies/mL), respectively. Forty-four patients (22.7%) experienced an IRIS event at a median of 12 weeks after HAART initiation (IQR, 4-24 weeks after initiation); 22 events (50%) involved genital herpes, 10 (23%) involved genital warts, 4 (9.0%) involved molluscum contagiosum, and 4 (9.0%) involved varicella zoster virus infection. Five patients had mycobacterial infections, 4 had hepatitis B, 1 had Pneumocystis jirovecci infection, and 1 had Kaposi sarcoma. The strongest independent predictors of IRIS were younger age at initiation of HAART (P=.003), baseline CD4 cell percentage of <10% (odds ratio [OR], 2.97; IQR, 1.17-7.55) compared with >15%, and ratio of CD4 cell percentage to CD8 cell percentage of <0.15 (OR, 3.45; 95% confidence interval, 1.27-9.1) compared with >0.3. Approximately one-quarter of patients who start HAART experience an IRIS event. The majority are dermatological, in particular genital herpes and warts. Patients with advanced immunodeficiency at HAART initiation are at greatest risk of developing IRIS and should be appropriately screened and monitored.

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.

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

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.

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.

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.

Proposed clinical case definition for cytomegalovirus-immune recovery retinitis.

PubMed

Ruiz-Cruz, Matilde; Alvarado-de la Barrera, Claudia; Ablanedo-Terrazas, Yuria; Reyes-Terán, Gustavo

2014-07-15

Cytomegalovirus (CMV) retinitis has been extensively described in patients with advanced or late human immunodeficiency virus (HIV) disease under ineffective treatment of opportunistic infection and antiretroviral therapy (ART) failure. However, there is limited information about patients who develop active cytomegalovirus retinitis as an immune reconstitution inflammatory syndrome (IRIS) after successful initiation of ART. Therefore, a case definition of cytomegalovirus-immune recovery retinitis (CMV-IRR) is proposed here. We reviewed medical records of 116 HIV-infected patients with CMV retinitis attending our institution during January 2003-June 2012. We retrospectively studied HIV-infected patients who had CMV retinitis on ART initiation or during the subsequent 6 months. Clinical and immunological characteristics of patients with active CMV retinitis were described. Of the 75 patients under successful ART included in the study, 20 had improvement of CMV retinitis. The remaining 55 patients experienced CMV-IRR; 35 of those developed CMV-IRR after ART initiation (unmasking CMV-IRR) and 20 experienced paradoxical clinical worsening of retinitis (paradoxical CMV-IRR). Nineteen patients with CMV-IRR had a CD4 count of ≥50 cells/µL. Six patients with CMV-IRR subsequently developed immune recovery uveitis. There is no case definition for CMV-IRR, although this condition is likely to occur after successful initiation of ART, even in patients with high CD4 T-cell counts. By consequence, we propose the case definitions for paradoxical and unmasking CMV-IRR. We recommend close follow-up of HIV-infected patients following ART initiation. © 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.

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.

Same-day antiretroviral therapy (ART) initiation in pregnancy is not associated with viral suppression or engagement in care: A cohort study.

PubMed

Langwenya, Nontokozo; Phillips, Tamsin K; Brittain, Kirsty; Zerbe, Allison; Abrams, Elaine J; Myer, Landon

2018-06-01

Many prevention of mother-to-child HIV transmission programmes across Africa initiate HIV-infected (HIV positive) pregnant women on lifelong antiretroviral therapy (ART) on the first day of antenatal care ("same-day" initiation). However, there are concerns that same-day initiation may limit patient preparation before starting ART and contribute to subsequent non-adherence, disengagement from care and raised viral load. We examined if same-day initiation was associated with viral suppression and engagement in care during pregnancy. Consecutive ART-eligible pregnant women making their first antenatal care (ANC) visit at a primary care facility in Cape Town, South Africa were enrolled into a prospective cohort between March 2013 and June 2014. Before July 2013, ART eligibility was based on CD4 cell count ≤350 cells/μL ("Option A"), with a 1 to 2 week delay from the first ANC visit to ART initiation for patient preparation; thereafter all women were eligible regardless of CD4 cell count ("Option B+") and offered ART on the same day as first ANC visit. Women were followed with viral load testing conducted separately from routine ART services, and engagement in ART services was measured using routinely collected clinic, pharmacy and laboratory records through 12 months postpartum. Among 628 HIV-positive women (median age, 28 years; median gestation at ART start, 21 weeks; 55% newly diagnosed with HIV), 73% initiated ART same-day; this proportion was higher under Option B+ versus Option A (85% vs. 20%). Levels of viral suppression (viral load <50 copies/mL) at delivery (74% vs. 82%) and 12 months postpartum (74% vs. 71%) were similar under same-day versus delayed initiation respectively. Findings were consistent when viral suppression was defined at <1000 copies/mL, after adjustment for demographic/clinical measures and across subgroups of age, CD4 and timing of HIV diagnosis. Time to first viral rebound following initial suppression did not differ by timing of ART initiation nor did engagement in care through 12 months postpartum (same-day = 73%, delayed = 73%, p = 0.910). These data suggest that same-day ART initiation during pregnancy is not associated with lower levels of engagement in care or viral suppression through 12 months post-delivery in this setting, providing reassurance to ART programmes implementing Option B+. © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Evaluation of the United States Public Health Service guidelines for discontinuation of anti-CMV therapy after immune recovery in patients with CMV retinitis

PubMed Central

Holbrook, Janet T.; Colvin, Ryan; Van Natta, Mark L.; Thorne, Jennifer E.; Bardsley, Mark; Jabs, Douglas A.

2011-01-01

Purpose To evaluate US Public Health Service (USPHS) guidelines for discontinuing anti-CMV therapy in patients with AIDS who have immune recovery and quiescent retinitis after initiating highly active anti-retroviral therapy (HAART). Design Cohort study of patients with CMV retinitis (Longitudinal Study of Ocular Complications of AIDS). Methods Participants had CMV retinitis and CD4+ T-cell counts of 50 cells/uL or fewer enrolled from 1998 to 2009 who demonstrated sustained immune recovery (two consecutive CD4+ T-cell counts of 100 cells/uL or more at least 6 months apart) and inactive retinitis. Participants were classified into 2 groups according to anti-CMV treatment after immune recover: (1) continued anti-CMV therapy and (2) discontinued therapy. We evaluated survival, visual acuity, and CMV retinitis activity; we employed propensity scores to adjust for confounding factors for these analyses. Results Of 152 participants reviewed, 71 demonstrated immune recovery; 37 of whom discontinued therapy and 34 who continued therapy. At immune recovery, participants continuing therapy tended to be older (44 vs 40 years, P=0.09), have bilateral retinitis (53% vs 32%, P=0.10), and have lower CD4+ T-cell counts (148 vs 207 cells/μL, P<0.001). There were no statistical differences in any of the clinical outcomes (death, retinitis progress, visual acuity or incidence of bilateral retinitis). Both groups lost visual acuity during follow-up, on average 1.2 letters per year (P<0.01). Conclusion Discontinuation of anti-CMV therapy after immune recovery did not increase the risk of poor outcomes. These results support the current guidelines for discontinuation of anti-CMV therapy after achievement of sustained immune recovery. PMID:21742304

Phase I study of 2'-3'-dideoxyinosine administered orally twice daily to patients with AIDS or AIDS-related complex and hematologic intolerance to zidovudine.

PubMed

Connolly, K J; Allan, J D; Fitch, H; Jackson-Pope, L; McLaren, C; Canetta, R; Groopman, J E

1991-11-01

To evaluate the safety and hematologic tolerance of 2'-3'-dideoxyinosine (didanosine, ddI) in subjects with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex and prior hematologic intolerance to zidovudine. A Phase I trial with two dose groups at a single-center, university-affiliated hospital ambulatory care center. Of 30 subjects enrolled, 21 had AIDS and nine had AIDS-related complex. All had CD4 lymphocyte counts less than 0.2 x 10(9)/L at entry. Didanosine was administered orally twice daily at a total daily dose of 750 mg or 1,500 mg for 12 weeks. Subjects who completed the 12-week study continued to receive ddI at the lower dose. All subjects were monitored for toxicity. Virologic and immunologic response markers were also measured. For the group as a whole, there was no significant decrease in mean hemoglobin level or leukocyte or platelet counts. The dose-limiting toxicity was peripheral neuropathy. Other significant toxicities included pancreatitis and hypocalcemia. Uric acid elevations were common but were without clinical consequence. A sustained decrease in serum p24 antigen of at least 50% was noted in 42% of subjects who were p24 antigen-positive at entry. The mean CD4 lymphocyte count showed an initial increase that was not sustained over the 12-week study. All subjects remained anergic to skin testing. Didanosine is well tolerated hematologically in some patients with prior significant hematologic intolerance to zidovudine. The toxicity profile for ddI differs from that of zidovudine and includes peripheral neuropathy and pancreatitis. Changes in CD4 lymphocyte number and HIV p24 antigen levels in some patients suggest antiviral activity of ddI in this population.

Late HIV Diagnosis: Proposed Common Definitions and Associations With Short-Term Mortality.

PubMed

Jiang, Hongbo; Xie, Nianhua; Liu, Jianhua; Zhang, Zhixia; Liu, Li; Yao, Zhongzhao; Wang, Xia; Nie, Shaofa

2015-09-01

The aim of this study was to present a definition of late presentation according to different time periods between initial diagnosis of human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) diagnosis which would reliably identify individuals with high risk of mortality within 1 year of diagnosis, and could be used as a suggested common definition.Data of individuals diagnosed from 1994 to February 2012 in Wuhan, China were extracted retrospectively from the national HIV surveillance system. Four time periods (1, 3, 6, and 12 months) combined with the European consensus definition of advanced HIV disease (AHD) were compared. The predictive ability of each definition for identifying an individual who died within 1 year after HIV diagnosis was assessed.A total of 980 patients were included, of whom 289 (29.49%), 324 (33.06%), 353 (36.02%), and 387 (39.49%) were defined as AHD according to the definition of a CD4 count <200 cells/μL or AIDS-defining event (ADE) within 1, 3, 6, and 12 months of HIV diagnosis, respectively. One hundred twenty-seven (12.96%) patients died within 1 year of diagnosis. The highest Youden's index and largest area under the curve were presented in time period within 3 months. Time period within 1 month presented the highest consistency rate, positive likelihood ratio, and kappa value. Longer time periods increased the sensitivity but decreased the specificity.Given the European consensus definitions and the current results, we suggested that AHD could be defined as "a first-reported CD4 count <200 cells/μL or an ADE within 1 month after HIV diagnosis." "Late presentation" could be defined as "a first-reported CD4 count <350 cells/μL or an ADE within 1 month after HIV diagnosis."

Evaluation of the United States public health service guidelines for discontinuation of anticytomegalovirus therapy after immune recovery in patients with cytomegalovirus retinitis.

PubMed

Holbrook, Janet T; Colvin, Ryan; van Natta, Mark L; Thorne, Jennifer E; Bardsley, Mark; Jabs, Douglas A

2011-10-01

To evaluate United States Public Health Service (USPHS) guidelines for discontinuing anticytomegalovirus (CMV) therapy in patients with AIDS who have immune recovery and quiescent retinitis after initiating highly active antiretroviral therapy. Cohort study of patients with CMV retinitis (Longitudinal Study of Ocular Complications of AIDS). Participants had CMV retinitis and CD4+ T-cell counts of 50 cells/μL or fewer enrolled from 1998 through 2009 who demonstrated sustained immune recovery (2 consecutive CD4+ T-cell counts of 100 cells/μL or more at least 6 months apart) and inactive retinitis. Participants were classified into 2 groups according to anti-CMV treatment after immune recover: (1) continued anti-CMV therapy and (2) discontinued therapy. We evaluated survival, visual acuity, and CMV retinitis activity; we used propensity scores to adjust for confounding factors for these analyses. Of 152 participants reviewed, 71 demonstrated immune recovery, 37 of whom discontinued therapy and 34 of whom continued therapy. At immune recovery, participants continuing therapy tended to be older (44 vs 40 years; P = .09), have bilateral retinitis (53% vs 32%; P = .10), and have lower CD4+ T-cell counts (148 vs 207 cells/μL; P < .001). There were no statistical differences in any of the clinical outcomes (death, retinitis progress, visual acuity, or incidence of bilateral retinitis). Both groups lost visual acuity during follow-up, on average 1.2 letters per year (P < .01). Discontinuation of anti-CMV therapy after immune recovery did not increase the risk of poor outcomes. These results support the current guidelines for discontinuation of anti-CMV therapy after achievement of sustained immune recovery. Copyright © 2011 Elsevier Inc. All rights reserved.

Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: investment needs, population health gains, and cost-effectiveness

PubMed Central

Hontelez, Jan A.C.; Chang, Angela Y.; Ogbuoji, Osondu; de Vlas, Sake J.; Bärnighausen, Till; Atun, Rifat

2016-01-01

Objective: We estimated the investment needs, population health gains, and cost-effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). Design: We adapted the established STDSIM model to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART). Methods: We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4+ cell count within these constraints. Results: Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4+ cell count is cost-effective under all constraints tested in the model, especially in demand-side constrained health systems because earlier initiation prevents loss-to-follow-up of patients not yet eligible. Changing guidelines under current demand-side constraints would avert 1.8 million infections at US$208 per life-year saved. Conclusion: Treatment eligibility at any CD4+ cell count would be cost-effective, even under health system constraints. Excessive loss-to-follow-up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial and requires strong, long-term commitment of policy-makers and donors to continue to allocate substantial parts of their budgets. PMID:27367487

Changing HIV treatment eligibility under health system constraints in sub-Saharan Africa: investment needs, population health gains, and cost-effectiveness.

PubMed

Hontelez, Jan A C; Chang, Angela Y; Ogbuoji, Osondu; de Vlas, Sake J; Bärnighausen, Till; Atun, Rifat

2016-09-24

We estimated the investment needs, population health gains, and cost-effectiveness of different policy options for scaling-up prevention and treatment of HIV in the 10 countries that currently comprise 80% of all people living with HIV in sub-Saharan Africa (Ethiopia, Kenya, Malawi, Mozambique, Nigeria, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe). We adapted the established STDSIM model to capture the health system dynamics: demand-side and supply-side constraints in the delivery of antiretroviral treatment (ART). We compared different scenarios of supply-side (i.e. health system capacity) and demand-side (i.e. health seeking behavior) constraints, and determined the impact of changing guidelines to ART eligibility at any CD4 cell count within these constraints. Continuing current scale-up would require US$178 billion by 2050. Changing guidelines to ART at any CD4 cell count is cost-effective under all constraints tested in the model, especially in demand-side constrained health systems because earlier initiation prevents loss-to-follow-up of patients not yet eligible. Changing guidelines under current demand-side constraints would avert 1.8 million infections at US$208 per life-year saved. Treatment eligibility at any CD4 cell count would be cost-effective, even under health system constraints. Excessive loss-to-follow-up and mortality in patients not eligible for treatment can be avoided by changing guidelines in demand-side constrained systems. The financial obligation for sustaining the AIDS response in sub-Saharan Africa over the next 35 years is substantial and requires strong, long-term commitment of policy-makers and donors to continue to allocate substantial parts of their budgets.

Kaposi’s Sarcoma in HIV-infected patients in South Africa: multi-cohort study in the antiretroviral therapy era

PubMed Central

Bohlius, Julia; Valeri, Fabio; Maskew, Mhairi; Prozesky, Hans; Garone, Daniela; Sengayi, Mazvita; Fox, Matthew P.; Davies, Mary-Ann; Egger, Matthias

2015-01-01

The incidence of Kaposi’s Sarcoma (KS) is high in South Africa but the impact of antiretroviral therapy (ART) is not well defined. We examined incidence and survival of KS in HIV-infected patients enrolled in South African ART programs. We analyzed data of three ART programs: Khayelitsha township and Tygerberg Hospital programs in Cape Town and Themba Lethu program in Johannesburg. We included patients aged >16 years. ART was defined as a regimen of at least three drugs. We estimated incidence rates of KS for patients on ART and not on ART. We calculated Cox models adjusted for age, sex and time-updated CD4 cell counts and HIV-1 RNA. 18,254 patients (median age 34.5 years, 64% female, median CD4 cell count at enrolment 105 cells/μL) were included. During 37,488 person-years follow-up 162 patients developed KS. The incidence was 1,682/100,000 person-years (95% confidence interval [CI] 1,406–2,011) among patients not receiving ART and 138/100,000 person-years (95% CI 102–187) among patients on ART. The adjusted hazard ratio comparing time on ART with time not on ART was 0.19 (95% CI 0.13–0.28). Low CD4 cell counts (time-updated) and male sex were also associated with KS. Estimated survival of KS patients at one year was 72.2% (95% CI 64.9–80.2) and higher in men than in women. The incidence of KS is substantially lower on ART than not on ART. Timely initiation of ART is essential to preventing KS and KS-associated morbidity and mortality in South Africa and other regions in Africa with a high burden of HIV. PMID:24729433

Effectiveness of an Integrated Approach to HIV and Hypertension Care in Rural South Africa: Controlled Interrupted Time-Series Analysis.

PubMed

Ameh, Soter; Klipstein-Grobusch, Kerstin; Musenge, Eustasius; Kahn, Kathleen; Tollman, Stephen; Gómez-Olivé, Francesc Xavier

2017-08-01

South Africa faces a dual burden of HIV/AIDS and noncommunicable diseases. In 2011, a pilot integrated chronic disease management (ICDM) model was introduced by the National Health Department into selected primary health care (PHC) facilities. The objective of this study was to assess the effectiveness of the ICDM model in controlling patients' CD4 counts (>350 cells/mm) and blood pressure [BP (<140/90 mm Hg)] in PHC facilities in the Bushbuckridge municipality, South Africa. A controlled interrupted time-series study was conducted using the data from patients' clinical records collected multiple times before and after the ICDM model was initiated in PHC facilities in Bushbuckridge. Patients ≥18 years were recruited by proportionate sampling from the pilot (n = 435) and comparing (n = 443) PHC facilities from 2011 to 2013. Health outcomes for patients were retrieved from facility records for 30 months. We performed controlled segmented regression to model the monthly averages of individuals' propensity scores using autoregressive moving average model at 5% significance level. The pilot facilities had 6% greater likelihood of controlling patients' CD4 counts than the comparison facilities (coefficient = 0.057; 95% confidence interval: 0.056 to 0.058; P < 0.001). Compared with the comparison facilities, the pilot facilities had 1.0% greater likelihood of controlling patients' BP (coefficient = 0.010; 95% confidence interval: 0.003 to 0.016; P = 0.002). Application of the model had a small effect in controlling patients' CD4 counts and BP, but showed no overall clinical benefit for the patients; hence, the need to more extensively leverage the HIV program for hypertension treatment.

Time to Initiation of Antiretroviral Therapy Among Patients Who Are ART Eligible in Rwanda: Improvement Over Time

PubMed Central

Teasdale, Chloe A.; Wang, Chunhui; Francois, Uwinkindi; d’Amour Ndahimana, Jean; Vincent, Mutabazi; Sahabo, Ruben; El-Sadr, Wafaa M.; Abrams, Elaine J.

2016-01-01

Background Delayed initiation of antiretroviral therapy (ART) in eligible patients is a concern in resource-limited countries. Methods We analyzed data on HIV-positive patients ≥15 years enrolled at 41 ICAP-supported health care facilities in Rwanda, 2005–2010, to determine time to ART initiation among patients eligible at enrollment compared with those ineligible or of indeterminate eligibility who become eligible during follow-up. ART eligibility was based on CD4+ cell count (CD4+) and WHO staging; patients lacking CD4+ and WHO stage were considered indeterminate. Cumulative incidence of reaching ART eligibility and to ART initiation after eligibility was generated using competing risk estimators. Results A total of 31,033 ART-naive adults were enrolled; 64.2% were female. At enrollment, 10,158 (32.7%) patients were ART eligible, 13,372 (43.1%) were ineligible for ART, and 7503 (24.2%) patients were indeterminate. Among patients retained in care pre-ART eligibility, 17.9% [95% confidence interval (CI): 17.2 to 18.6] of ineligible and 22.8% (95% CI: 21.7 to 23.8) of indeterminate patients at enrollment reached ART eligibility within 12 months. Cumulative incidence of ART initiation within 3 months for patients eligible at enrollment was 77.2% (95% CI: 76.4 to 78.0) compared with 67.9% (95% CI: 66.4 to 69.3) for ineligible and 63.8% (95% CI: 61.9 to 65.8) for patients with indeterminate eligibility at enrollment (P < 0.05). Over the study period, there was more rapid ART initiation for patients who became ART eligible. Conclusions We found higher rates of ART initiation within 3 months among patients who were ART eligible at enrollment compared with those who reached eligibility during follow-up. From 2006 to 2011, earlier initiation of ART after eligibility was observed likely reflecting improved program quality. PMID:25415291

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

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

Determinants of Mortality and Loss to Follow-Up among Adults Enrolled in HIV Care Services in Rwanda

PubMed Central

Wang, Chunhui; Lahuerta, Maria; Nuwagaba-Biribonwoha, Harriet; Tayebwa, Edwin; Ingabire, Eugenie; Ingabire, Pacifique; Sahabo, Ruben; Twyman, Peter; Abrams, Elaine J.

2014-01-01

Background Antiretroviral therapy (ART) improves morbidity and mortality in patients with HIV, however high rates of loss to follow-up (LTF) and mortality have been documented in HIV care and treatment programs. Methods We analyzed routinely-collected data on HIV-infected patients ≥15 years enrolled at 41 healthcare facilities in Rwanda from 2005 to 2010. LTF was defined as not attending clinic in the last 12 months for pre-ART patients and 6 months for ART patients. For the pre-ART period, sub-distribution hazards models were constructed to estimate LTF and death to account for competing risks. Kaplan-Meier (KM) and Cox proportional hazards models were used for patients on ART. Results 31,033 ART-naïve adults were included, 64% were female and 75% were WHO stage I or II at enrollment. 17,569 (56%) patients initiated ART. Pre-ART competing risk estimates of LTF at 2 years was 11.2% (95%CI, 10.9–11.6%) and 2.9% for death (95%CI 2.7–3.1%). Among pre-ART patients, male gender was associated with higher LTF (adjusted sub-hazard ratio (aSHR) 1.3, 95%CI 1.1–1.5) and death (aSHR 1.7, 95%CI 1.4–2.1). Low CD4 count (CD4<100 vs. ≥350 aSHR 0.2, 95%CI 0.1–0.3) and higher WHO stage (WHO stage IV vs. stage I aSHR 0.4, 95%CI 0.2–0.6) were protective against pre-ART LTF. KM estimates for LTF and death in ART patients at 2 years were 4.4% (95%CI 4.4–4.5%) and 6.3% (95%CI 6.2–6.4%). In patients on ART, male gender was associated with LTF (adjusted hazard ratio (AHR) 1.4, 95%CI 1.2–1.7) and death (AHR1.3, 95%CI 1.2–1.5). Mortality was higher for ART patients ≥40 years and in those with lower CD4 count at ART initiation. Conclusions Low rates of LTF and death were founds among pre-ART and ART patients in Rwanda but greater efforts are needed to retain patients in care prior to ART initiation, particularly among those who are healthy at enrollment. PMID:24454931

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.

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.

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.

Effect of Micronutrient Supplementation on Disease Progression in Asymptomatic, Antiretroviral-Naive, HIV-Infected Adults in Botswana A Randomized Clinical Trial

PubMed Central

Baum, Marianna K.; Campa, Adriana; Lai, Shenghan; Martinez, Sabrina Sales; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W.; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2015-01-01

IMPORTANCE Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. OBJECTIVE To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), seleniumalone, or multivitamins with selenium vs placebo inafactorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. INTERVENTIONS Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. MAIN OUTCOMES AND MEASURES Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. RESULTS There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. CONCLUSIONS AND RELEVANCE In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly PMID:24281460

Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial.

PubMed

Baum, Marianna K; Campa, Adriana; Lai, Shenghan; Sales Martinez, Sabrina; Tsalaile, Lesedi; Burns, Patricia; Farahani, Mansour; Li, Yinghui; van Widenfelt, Erik; Page, John Bryan; Bussmann, Hermann; Fawzi, Wafaie W; Moyo, Sikhulele; Makhema, Joseph; Thior, Ibou; Essex, Myron; Marlink, Richard

2013-11-27

Micronutrient deficiencies occur early in human immunodeficiency virus (HIV) infection, and supplementation with micronutrients may be beneficial; however, its effectiveness has not been investigated early in HIV disease among adults who are antiretroviral therapy (ART) naive. To investigate whether long-term micronutrient supplementation is effective and safe in delaying disease progression when implemented early in adults infected with HIV subtype C who are ART-naive. Randomized clinical trial of supplementation with either daily multivitamins (B vitamins and vitamins C and E), selenium alone, or multivitamins with selenium vs placebo in a factorial design for 24 months. The study was conducted in 878 patients infected with HIV subtype C with a CD4 cell count greater than 350/μL who were not receiving ART at Princess Marina Hospital in Gaborone, Botswana, between December 2004 and July 2009. Daily oral supplements of B vitamins and vitamins C and E, selenium alone, or multivitamins plus selenium, compared with placebo. Reaching a CD4 cell count less than 200/μL until May 2008; after this date, reaching a CD4 cell count of 250/μL or less, consistent with the standard of care in Botswana for initiation of ART at the time of the study. There were 878 participants enrolled and randomized into the study. All participants were ART-naive throughout the study. In intent-to-treat analysis, participants receiving the combined supplement of multivitamins plus selenium had a significantly lower risk vs placebo of reaching CD4 cell count 250/μL or less (adjusted hazard ratio [HR], 0.46; 95% CI, 0.25-0.85; P = .01; absolute event rate [AER], 4.79/100 person-years; censoring rate, 0.92; 17 events; placebo AER, 9.22/100 person-years; censoring rate, 0.85; 32 events). Multivitamins plus selenium in a single supplement, vs placebo, also reduced the risk of secondary events of combined outcomes for disease progression (CD4 cell count ≤250/μL, AIDS-defining conditions, or AIDS-related death, whichever occurred earlier [adjusted HR, 0.56; 95% CI, 0.33-0.95; P = .03; AER, 6.48/100 person-years; censoring rate, 0.90; 23 events]). There was no effect of supplementation on HIV viral load. Multivitamins alone and selenium supplementation alone were not statistically different from placebo for any end point. Reported adverse events were adjudicated as unlikely to be related to the intervention, and there were no notable differences in incidence of HIV-related and health-related events among study groups. In ART-naive HIV-infected adults, 24-month supplementation with a single supplement containing multivitamins and selenium was safe and significantly reduced the risk of immune decline and morbidity. Micronutrient supplementation may be effective when started in the early stages of HIV disease.

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

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.

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.

A retrospective study of HIV, antiretroviral therapy, and pregnancy-associated hypertension among women in Lusaka, Zambia.

PubMed

Stoner, Marie C D; Vwalika, Bellington; Smid, Marcela C; George, Shalin; Chi, Benjamin H; Stringer, Elizabeth M; Stringer, Jeffrey S A

2016-09-01

To investigate the association between HIV, antiretroviral therapy (ART), and pregnancy-associated hypertension (PAH) in an HIV-endemic setting. A retrospective cohort study was undertaken of pregnant women for whom information was recorded between February 2006 and December 2012 in the Zambia Electronic Perinatal Record System, which captures data from 25 facilities in Lusaka, Zambia. PAH was defined as eclampsia, pre-eclampsia, hypertension, or elevated blood pressure (>140/80mm Hg) during delivery admission. Logistic regression estimated the odds of PAH among women by HIV serostatus, and by most recent CD4 T lymphocyte count and ART status among women with HIV infection. Among 249 771 women included in the analysis, 5354 (2.1%) had PAH. Compared with women without HIV infection, women with HIV infection not receiving ART had lower odds of PAH (adjusted odds ratio [AOR] 0.86, 95% confidence interval 0.78-0.95), whereas those with HIV infection who had initiated ART had higher odds of PAH (AOR 1.15, 95% CI 1.01-1.32). No association was found between PAH and timing of ART initiation or CD4 lymphocyte count. In a large African urban cohort, women with untreated HIV infection had the lowest odds of PAH. Treatment with ART could increase PAH risk beyond that of women without HIV infection and those with untreated infection. Published by Elsevier Ireland Ltd.

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.

[Recommendations of the CEVIHP/SEIP/AEP/PNS on antiretroviral treatment in HIV-infected children and teenagers].

PubMed

Ramos, José Tomás; de José, María Isabel; Polo, Rosa; Fortuny, Claudia; Mellado, María José; Muñoz-Fernández, María Angeles; Beceiro, José; Bertrán, José María; Calvo, Cristina; Chamorro, Lourdes; Ciria, Luis; Guillén, Sara; González-Montero, Raúl; González-Tomé, María Isabel; Gurbindo, María Dolores; Martín-Fontelos, Pablo; Martínez-Pérez, Jorge; Moreno, David; Muñoz-Almagro, María Carmen; Mur, Antonio; Navarro, María Luisa; Otero, Carmen; Rojo, Pablo; Rubio, Bárbara; Saavedra, Jesús

2005-05-01

To update antiretroviral recommendations in antiretroviral therapy (ART) in HIV-infected children and adolescents. Theses guidelines have been formulated by a panel of members of the Plan Nacional sobre el SIDA (PNS) and the Asociacion Espanola de Pediatria (AEP) by reviewing the current available evidence of efficacy, safety, and pharmacokinetics in pediatric studies. Three levels of evidence have been defined according to the source of data: Level A: randomized and controlled studies; Level B: Cohort and case-control studies; Level C: Descriptive studies and experts' opinion. When to start ART should be made on an individual basis, discussed with the family, considering the risk of progression according to age, CD4 and viral load, the ART-related complications and adherence. The ART goal is to reach a maximum and durable viral suppression. This is not always possible, even with clinical and immunologic improvement. The difficulties of permanent adherence and side-effects are resulting in a more conservative trend to initiate ART, and to less toxic and simpler strategies. Currently, combinations of at least three drugs are of first choice both in acute and chronic infection. They must include 2 NA 1 1 NN or 2 NA 1 1 PI. ART is recommended in all symptomatic patients and, with few exceptions, in all infants in the first year of life. Older asymptomatic children should start ART according to CD4 count, especially CD4 percentage, that vary with age. Despite potent salvage therapies, it is common not to reach viral undetectability. Therapeutical options when ART fails are scarce due to cross-resistance. The cause of failure must be identified. Occasionally, there exists clinical and/or immunological progression, and a change of therapy with at least two new drugs still active for the patient, is warranted with the aim of increasing the CD4 count to a lower level of risk. Toxicity and adherence must be regularly monitored. Some aspects about post exposure prophylaxis and coinfection with HCV or HBV are discussed. A higher level of evidence with regard to ART effectiveness and toxicity in pediatrics is currently available, leading to a more conservative and individualized approach. Clinical symptoms and CD4 count are the main determinants to start and change ART.

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

Genome-wide expression profiling analysis to identify key genes in the anti-HIV mechanism of CD4+ and CD8+ T cells.

PubMed

Gao, Lijie; Wang, Yunqi; Li, Yi; Dong, Ya; Yang, Aimin; Zhang, Jie; Li, Fengying; Zhang, Rongqiang

2018-07-01

Comprehensive bioinformatics analyses were performed to explore the key biomarkers in response to HIV infection of CD4 + and CD8 + T cells. The numbers of CD4 + and CD8 + T cells of HIV infected individuals were analyzed and the GEO database (GSE6740) was screened for differentially expressed genes (DEGs) in HIV infected CD4 + and CD8 + T cells. Gene Ontology enrichment, KEGG pathway analyses, and protein-protein interaction (PPI) network were performed to identify the key pathway and core proteins in anti-HIV virus process of CD4 + and CD8 + T cells. Finally, we analyzed the expressions of key proteins in HIV-infected T cells (GSE6740 dataset) and peripheral blood mononuclear cells(PBMCs) (GSE511 dataset). 1) CD4 + T cells counts and ratio of CD4 + /CD8 + T cells decreased while CD8 + T cells counts increased in HIV positive individuals; 2) 517 DEGs were found in HIV infected CD4 + and CD8 + T cells at acute and chronic stage with the criterial of P-value <0.05 and fold change (FC) ≥2; 3) In acute HIV infection, type 1 interferon (IFN-1) pathway might played a critical role in response to HIV infection of T cells. The main biological processes of the DEGs were response to virus and defense response to virus. At chronic stage, ISG15 protein, in conjunction with IFN-1 pathway might play key roles in anti-HIV responses of CD4 + T cells; and 4) The expression of ISG15 increased in both T cells and PBMCs after HIV infection. Gene expression profile of CD4 + and CD8 + T cells changed significantly in HIV infection, in which ISG15 gene may play a central role in activating the natural antiviral process of immune cells. © 2018 Wiley Periodicals, Inc.

Epidemiological and clinical characteristics of hepatitis B virus in HIV-infected patients in Guangdong, China.

PubMed

Huang, S M; Cai, W P; Hu, F Y; Lan, Y; Liao, B L; Chen, Y P; Tang, X P

2016-09-01

This study investigated the epidemiological and clinical characteristics of hepatitis B virus (HBV) in HIV-infected adults at the time of antiretroviral therapy (ART) initiation in Guangdong province, China. A total of 2793 HIV-infected adults were enrolled between January 2004 and September 2011. Demographic data and laboratory parameters were collected, HBV-DNA levels were measured, and HBV genotypes were identified before ART initiation. The prevalence of hepatitis B surface antigen (HBsAg) in HIV-infected patients was 13.2%. A total of 266 HIV/HBV co-infected patients and 1469 HIV mono-infected patients were recruited. The median alanine aminotransferase and aspartate aminotransferase levels of HIV/HBV co-infected patients were higher than HIV mono-infected patients (32 U/L vs. 22 U/L, p < 0.001 and 35 U/L vs. 24 U/L, p < 0.001, respectively), whereas the median CD4 cell count of HIV/HBV co-infected patients was lower than HIV mono-infected patients (59 cells/mm(3) vs. 141 cells/mm(3), p < 0.001). The level of CD4 cell count was lower in hepatitis B e-antigen (HBeAg)-positive co-infected patients than HBeAg-negative patients (36 cells/mm(3) vs. 69 cells/mm(3), p = 0.014). A similar result was found in high level of HBV-DNA and low level of HBV-DNA groups (33 cells/mm(3) vs. 89 cells/mm(3), p < 0.001). HBV genotypes were classified as genotypes B and C. Patients infected with genotypes B and C differed significantly in terms of proportion of those who were HBeAg-positive (40.5% vs. 62.2%, p = 0.014). This study indicates a high prevalence of HBsAg in HIV-infected adults in Guangdong. The level of CD4 cell count in HIV/HBV co-infected patients was much lower than HIV mono-infected patients, especially in patients who were HBeAg-positive and had a high level of HBV-DNA. The predominant HBV genotype in HIV/HBV co-infected patients is genotype B. © The Author(s) 2015.

Is human immunodeficiency virus (HIV) stage an independent risk factor for altering the periodontal status of HIV-positive patients? A South African study.

PubMed

John, Cathy Nisha; Stephen, Lawrence Xavier; Joyce Africa, Charlene Wilma

2013-12-03

The immunosuppresion in HIV patients makes them highly susceptible to microbial infections. The aim of the study was to establish whether HIV stage (as depicted by CD4+ T lymphocyte counts) could independently be associated with periodontal status (as revealed by the measurement of clinical indices). One hundred and twenty HIV-infected patients attending an infectious diseases clinic in the Western Cape, South Africa were included in the study. The periodontal clinical indices such as plaque index, gingival index, pocket probing depth and clinical attachment levels were measured on the mesial aspect of the six Ramfjord teeth. The CD4 + T cell counts were taken from the patients' medical records and patients' HIV stage determined and grouped according to their CD4+ T cell counts into A (<200 cells /mm3), B (200-500 cells /mm3) and C (>500 cells /mm3). The mean age of 120 HIV-positive patients was 33.25 years and the mean CD4 + T cell count was 293.43 cells/mm3. The probing depth and clinical attachment loss were found to be significantly associated with the total CD4 + T cell counts but not with HIV stage. Significant correlations were found between age and all clinical indices except for clinical attachment loss. No correlation was found between age and HIV stage of the patients. The use of antiretroviral therapy was significantly associated with probing depth and clinical attachment loss, but not with plaque nor gingival index. Significant associations were observed between smoking and all of the clinical indices except for the gingival index. A significant association was observed between the use of interdental aids and all the clinical indices except for probing depth, while brushing was significantly associated with plaque index only. CD4 + T cell counts were significantly associated with brushing frequency (p = 0.0190) and the use of interdental aids (p = 0.0170). The findings of this study conclude that HIV stage, ART and age are not independent risk factors for changes in the periodontal status of HIV-positive subjects but rather that smoking and oral hygiene habits determine their susceptibility to disease.

An update and review of antiretroviral therapy.

PubMed

Piacenti, Frank J

2006-08-01

The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16-20 pills/day. These treatment barriers often led to patient nonadherence, with subsequent treatment failure and development of resistant strains. The CD4 count and viral load are the most important surrogate markers used to determine if treatment is indicated. Current guidelines suggest starting treatment in patients who are symptomatic with an acquired immunodeficiency syndrome-defining illness regardless of CD4 count or viral load, as well as in asymptomatic patients with a CD4 count of 350 cells/mm(3) or below. In patients with CD4 counts above 350 cells/mm(3) and viral loads above 100,000 copies/ml, some clinicians prefer to defer treatment, whereas others will consider starting therapy; treatment is deferred in patients with CD4 counts above 350 cells/mm(3) and viral load s below 100,000 copies/ml. If therapy is started, the selection of appropriate agents is based on comorbidities (liver disease, depression, cardiovascular disease), pregnancy status, adherence potential (dosage regimen, pill burden, dosing frequency), food restrictions (dosing with regard to meals), adverse drug effects, and potential drug-drug interactions. Within the last 8 years, newer antiretroviral agents have focused on ways to improve adherence, such as convenient dosing (fewer pills), pharmacokinetic and formulation changes to reduce dosing frequency or pill burden, and coformulated dosage forms that contain two or three drugs in one convenient pill. Other improvements include increased potency of newer agents, agents sensitive to a highly resistant virus, improved adverse-effect profile (e.g., less gastrointestinal effects, improved lipid profiles), as well as protease inhibitor boosting with ritonavir, which takes advantage of the potent cytochrome P450 inhibitory action of ritonavir. This review focuses on the concepts of antiretroviral therapy, barriers to successful antiretroviral treatment, developments to limit treatment barriers, and new drug entities for the treatment of HIV.

Basophil mediated pro-allergic inflammation in vehicle-emitted particles exposure

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

Zakharenko, Alexander M.

Despite of the fact that engine manufacturers develop a new technology to reduce exhaust emissions, insufficient attention given to particulate emissions. However, diesel exhaust particles are a major source of air-borne pollution, contain vast amount of polycyclic aromatic hydrocarbons (PAHs) and may have deleterious effects on the immune system, resulting in the induction and enhancement of pro-allergic processes. In the current study, vehicle emitted particles (VEP) from 2 different types of cars (diesel - D and gasoline - G) and locomotive (L) were collected. Overall, 129 four-week-old, male SPF-class Kunming mice were subcutaneously instilled with either low dose 100, 250more » or high dose, 500 mg/kg VEP and 15 mice were assigned as control group. The systemic toxicity was evaluated and alterations in the percentages of the CD3, CD4, CD8, CD16, CD25 expressing cells, basophils, eosinophils and neutrophils were determined. Basophil percentages were inversely associated with the PAH content of the VEPs, however basophil sensitization was more important than cell count in VEP exposure. Thus, the effects of VEP-PAHs emerge with the activation of basophils in an allergen independent fashion. Despite the increased percentage of CD4+ T cells, a sharp decrease in basophil counts at 500 mg/kg of VEP indicates a decreased inhibitory effect of CD16+ monocytes on the proliferation of CD4+ T cell and suppressed polarization into a Th2 phenotype. Therefore, although the restrictions for vehicles emissions differ between countries, follow up studies and strict regulations are needed. - Highlights: • Basophil sensitization is more important than cell count in VEP exposure. • CD16+ cells are more effective than basophils on CD4+ T cell proliferation. • CD16+ and CD16- monocytes respond to VEP exposure in opposite directions. • CD8+ T cell proliferation is inhibited by all doses of VEPs. • Globally, more stringent standards are needed for vehicle particle emissions.« less

Frequency, pattern, and extent of skin diseases in relation to CD4+ cell count among adults with human immunodeficiency virus infection or acquired immunodeficiency syndrome in Osogbo, southwestern Nigeria.

PubMed

Akinboro, Adeolu Oladayo; Onayemi, Olaniyi; Mejiuni, Ayodele D

2014-04-01

Skin diseases characterize all stages of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) and contribute significantly to associated morbidity and mortality. The aim of this study was to document the prevalences, patterns, and extents (severity) of skin diseases and their relationships with immunologic status in HIV/AIDS patients. A total of 140 HIV/AIDS patients in different stages of HIV infection and 140 controls were recruited. Skin diseases were documented and CD4+ cell counts determined in all subjects. Severity was assessed according to the body surface area affected (using the Wallace rule of nines and the rule of palm) for lesions that tended to be widespread. The number of digits involved was counted for lesions involving the nails. Intensity of pain was graded for specific conditions such as herpes zoster. Chi-squared statistics and Pearson correlations were determined. Mean±standard deviation age was 35.04±8.83 years in the patient group and 32.21±8.30 years in the control group. The prevalences and patterns of skin diseases in HIV/AIDS patients were similar to those reported in previous studies. Most commonly found dermatoses were oral candidiasis (n=28, 20.0%), pruritic papular eruption (n=27, 19.3%), xeroderma (n=23, 16.4%), dermatophytosis (n=22, 15.7%), and fluffy hair (n=19, 13.6%). The presence of specific skin lesions represented a better correlate with immunosuppression than cutaneous extents. However, the extents of viral warts and multiple blue–black nails correlated significantly with CD4+ cell count. The presence of a lighter hair color phenotype signifies a lower CD4+ cell count than a softer hair phenotype. The presence of specific skin lesions correlates more strongly with a low CD4+ cell count than does the extent of their distribution, except in cases of viral warts. The presence of and higher numbers of nails affected with blue–black nail hyperpigmentation suggest severe immunosuppression.

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

Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity.

PubMed

Kousin-Ezewu, Onajite; Azzopardi, Laura; Parker, Richard A; Tuohy, Orla; Compston, Alastair; Coles, Alasdair; Jones, Joanne

2014-06-17

To test the hypothesis that accelerated peripheral blood mononuclear cell recovery after alemtuzumab treatment of multiple sclerosis is associated with recurrent disease activity and to investigate the claim that CD4 counts greater than 388.5 × 10(6) cells/mL at 12 months can be used to identify patients who may benefit from further treatment. A total of 108 patients were followed for a median of 99 months post alemtuzumab. Patients were classified as active or nonactive after each cycle of treatment based on clinical relapse, increasing disability, or new T2/enhancing MRI lesions. These outcomes were correlated with CD4, CD8, CD19, CD56+ NK, and monocyte counts. Of 108 patients, 56 (52%) relapsed at some point during follow-up. Mean annualized relapse rate after alemtuzumab was 0.17 vs 1.67 prior to treatment (equating to a 90% reduction). Of 108 patients, 28 (26%) met the criteria for sustained accumulation of disability. Median time to the lower limit of normal for CD19, CD8, and CD4 was 3, 19.5, and 32 months, respectively. There was no significant difference in the recovery of any cell population between patients with and without disease activity or accumulation of disability after treatment. This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab. © 2014 American Academy of Neurology.

CD4 T cell decline following HIV seroconversion in individuals with and without CXCR4-tropic virus.

PubMed

Ghosn, Jade; Bayan, Tatiana; Meixenberger, Karolin; Tran, Laurent; Frange, Pierre; d'Arminio Monforte, Antonella; Zangerle, Robert; de Mendoza, Carmen; Krastinova, Evguenia; Porter, Kholoud; Meyer, Laurence; Chaix, Marie-Laure

2017-10-01

The natural clinical and immunological courses following HIV seroconversion with CXCR4-tropic or dual-mixed (X4/DM) viruses are controversial. We compared spontaneous immunological outcome in patients harbouring an X4/DM virus at the time of seroconversion with those harbouring a CCR5-tropic (R5) virus. Data were included from patients participating in CASCADE, a large cohort collaboration of HIV seroconverters, with ≥2 years of follow-up since seroconversion. The HIV envelope gene was sequenced from frozen plasma samples collected at enrolment, and HIV tropism was determined using Geno2Pheno (false-positive rate 10%). The spontaneous CD4 T cell evolution was compared by modelling CD4 kinetics using linear mixed-effects models with random intercept and random slope. A total of 1387 patients were eligible. Median time between seroconversion and enrolment was 1 month (range 0-3). At enrolment, 202 of 1387 (15%) harboured an X4/DM-tropic virus. CD4 decrease slopes were not significantly different according to HIV-1 tropism during the first 30 months after seroconversion. No marked change in these results was found after adjusting for age, year of seroconversion and baseline HIV viral load. Time to antiretroviral treatment initiation was not statistically different between patients harbouring an R5 (20.76 months) and those harbouring an X4/DM-tropic virus (22.86 months, logrank test P = 0.32). Conclusions: In this large cohort collaboration, 15% of the patients harboured an X4/DM virus close to HIV seroconversion. Patients harbouring X4/DM-tropic viruses close to seroconversion did not have an increased risk of disease progression, estimated by the decline in CD4 T cell count or time to combined ART initiation. © 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.

Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency.

PubMed

John, G C; Nduati, R W; Mbori-Ngacha, D; Overbaugh, J; Welch, M; Richardson, B A; Ndinya-Achola, J; Bwayo, J; Krieger, J; Onyango, F; Kreiss, J K

1997-01-01

The presence of human immunodeficiency virus type 1 (HIV-1) in genital secretions may be a determinant of vertical HIV-1 transmission. Cervical and vaginal secretions from HIV-1-seropositive pregnant women were evaluated to determine prevalence and correlates of HIV-1-infected cells in the genital tract. HIV-1 DNA was detected by polymerase chain reaction in 32% of 212 cervical and 10% of 215 vaginal specimens. Presence of HIV-1 DNA in the cervix was associated with cervical mucopus and a significantly lower absolute CD4 cell count (354 vs. 469, P < .001). An absolute CD4 cell count <200 was associated with a 9.6-fold increased odds of cervical HIV-1 DNA detection compared with a count > or = 500 (95% confidence interval, 2.8-34.2). Detection of vaginal HIV- 1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin A deficiency. Presence of HIV-1-infected cells in genital secretions was associated with immunosuppression and abnormal cervical or vaginal discharge.

Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age.

PubMed

Malphettes, Marion; Carcelain, Guislaine; Saint-Mezard, Pierre; Leblond, Véronique; Altes, Hester Korthals; Marolleau, Jean-Pierre; Debré, Patrice; Brouet, Jean-Claude; Fermand, Jean-Paul; Autran, Brigitte

2003-03-01

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 x 10(6)/kg; P =.002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+ subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L-. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

Effect of deworming on disease progression markers in HIV-1-infected pregnant women on antiretroviral therapy: a longitudinal observational study from Rwanda.

PubMed

Ivan, Emil; Crowther, Nigel J; Mutimura, Eugene; Rucogoza, Aniceth; Janssen, Saskia; Njunwa, Kato K; Grobusch, Martin P

2015-01-01

Deworming human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) may be beneficial, particularly during pregnancy. We determined the efficacy of targeted and nontargeted antihelminth therapy and its effects on Plasmodium falciparum infection status, hemoglobin levels, CD4 counts, and viral load in pregnant, HIV-positive women receiving ART. Nine hundred eighty HIV-infected pregnant women receiving ART were examined at 2 visits during pregnancy and 2 postpartum visits within 12 weeks. Women were given antimalarials when malaria-positive whereas albendazole was given in a targeted (n = 467; treatment when helminth stool screening was positive) or nontargeted (n = 513; treatment at all time points, with stool screening) fashion. No significant differences were noted between targeted and nontargeted albendazole treatments for the variables measured at each study visit except for CD4 counts, which were lower (P < .05) in the latter group at the final visit. Albendazole therapy was associated with favorable changes in subjects' hemoglobin levels, CD4 counts, and viral loads, particularly with helminth infections. Antihelminthic therapy reduces detectable viral load, and increases CD4 counts and hemoglobin levels in pregnant HIV-infected women with helminth coinfections receiving ART. © 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.

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.

[A case of both cryptococcal pneumonia and meningitis with idiopathic CD4+T-lymphocytopenia followed up over a long time].

PubMed

Anzai, Fumio; Yamamoto, Akito; Tannai, Noriyuki; Abe, Hideki; Tsuchiya, Kayoko; Kusajima, Kenji; Shimoide, Hisao; Nunomura, Maki

2009-07-01

A 62-year-old man had felt cold-like symptoms for 2 months. He visited a clinic for a health check in late July 1998 and chest X-ray film showed an infiltrative shadow in the left middle and lower lung fields. Next day he had a fever of 38.3 degrees C and felt breathless. Six days thereafter he had a cough, thick head and felt fatigue. Chest X-ray films showed other infiltrative shadows in the bilateral upper lung fields. He worked in a race track and was exposed to pigeons and seabirds at that time. Culture of sputum grew Cryptococcus neoformans. He was admitted and was treated with intravenous antifungal drugs. Cerebrospinal fluid examination revealed positive Indian ink stain for C. neoformans. The CD4 + T-lymphocyte count and CD8 + T-lymphocyte count were 143.4 cells/mm3 and 1288.8 cells/mm3 respectively, but without HIV infection. Cryptococcal pneumonia and meningitis with Idiopathic CD4 + T-lymphocytopenia was diagnosed. After induction therapy, the symptoms improved but abnormal shadows remained on chest X-ray films. Maintenance therapy has been continued at doses of 200 mg/day of fluconazole for 10 years. He has had no symptoms, but the abnormal X-ray shadow has persisted and the CD4 count has remained low during the same period.

[Barriers to ART initiation in HIV infected subjects and with treatment indication in Spain. Why don't they start their treatment? Bridgap Study].

PubMed

Viciana-Fernández, Pompeyo; Falcó, Vicenç; Castaño, Manuel; de los Santos-Gil, Ignacio; Olalla-Sierra, Julián; Hernando, Asunción; Deig, Elisabet; Clotet, Bonaventura; Knobel, Hernando; Podzamczer, Daniel; Pedrol, Pere Domingo

2015-01-01

In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented. A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART. A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count <500 cells/mm(3), 48%; having an uninfected sexual partner, 28%, and hepatitis C coinfection, 23%. Barriers due to, the physician, 55%; the patient, 28%; other limitations, 23%; and undetectable viral load, 6%. The majority of subjects with ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.