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Sample records for antiretroviral therapy compared

  1. Interruption or deferral of antiretroviral therapy reduces markers of bone turnover compared with continuous therapy: The SMART body composition substudy.

    PubMed

    Hoy, Jennifer; Grund, Birgit; Roediger, Mollie; Ensrud, Kristine E; Brar, Indira; Colebunders, Robert; Castro, Nathalie De; Johnson, Margaret; Sharma, Anjali; Carr, Andrew

    2013-06-01

    Bone mineral density (BMD) declines significantly in HIV patients on antiretroviral therapy (ART). We compared the effects of intermittent versus continuous ART on markers of bone turnover in the Body Composition substudy of the Strategies for Management of AntiRetroviral Therapy (SMART) trial and determined whether early changes in markers predicted subsequent change in BMD. For 202 participants (median age 44 years, 17% female, 74% on ART) randomized to continuous or intermittent ART, plasma markers of inflammation and bone turnover were evaluated at baseline and months 4 and 12; BMD at the spine (dual-energy X-ray absorptiometry [DXA] and computed tomography) and hip (DXA) was evaluated annually. Compared with the continuous ART group, mean bone-specific alkaline phosphatase (bALP), osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), N-terminal cross-linking telopeptide of type 1 collagen (NTX), and C-terminal cross-linking telopeptide of type 1 collagen (βCTX) decreased significantly in the intermittent ART group, whereas RANKL and the RANKL:osteoprotegerin (OPG) ratio increased (all p ≤ 0.002 at month 4 and month 12). Increases in bALP, osteocalcin, P1NP, NTX, and βCTX at month 4 predicted decrease in hip BMD at month 12, whereas increases in RANKL and the RANKL:OPG ratio at month 4 predicted increase in hip and spine BMD at month 12. This study has shown that compared with continuous ART, interruption of ART results in a reduction in markers of bone turnover and increase in BMD at hip and spine, and that early changes in markers of bone turnover predict BMD changes at 12 months.

  2. Individualization of antiretroviral therapy

    PubMed Central

    Pavlos, Rebecca; Phillips, Elizabeth J

    2012-01-01

    Antiretroviral therapy (ART) has evolved considerably over the last three decades. From the early days of monotherapy with high toxicities and pill burdens, through to larger pill burdens and more potent combination therapies, and finally, from 2005 and beyond where we now have the choice of low pill burdens and once-daily therapies. More convenient and less toxic regimens are also becoming available, even in resource-poor settings. An understanding of the individual variation in response to ART, both efficacy and toxicity, has evolved over this time. The strong association of the major histocompatibility class I allele HLA-B*5701 and abacavir hypersensitivity, and its translation and use in routine HIV clinical practice as a predictive marker with 100% negative predictive value, has been a success story and a notable example of the challenges and triumphs in bringing pharmacogenetics to the clinic. In real clinical practice, however, it is going to be the exception rather than the rule that individual biomarkers will definitively guide patient therapy. The need for individualized approaches to ART has been further increased by the importance of non-AIDS comorbidities in HIV clinical practice. In the future, the ideal utilization of the individualized approach to ART will likely consist of a combined approach using a combination of knowledge of drug, virus, and host (pharmacogenetic and pharmacoecologic [factors in the individual’s environment that may be dynamic over time]) information to guide the truly personalized prescription. This review will focus on our knowledge of the pharmacogenetics of the efficacy and toxicity of currently available antiretroviral agents and the current and potential utility of such information and approaches in present and future HIV clinical care. PMID:23226059

  3. Effect of directly observed antiretroviral therapy compared to self-administered antiretroviral therapy on adherence and virological outcomes among HIV-infected prisoners: a randomized controlled pilot study.

    PubMed

    White, Becky L; Golin, Carol E; Grodensky, Catherine A; Kiziah, C Nichole; Richardson, Amy; Hudgens, Michael G; Wohl, David A; Kaplan, Andrew H

    2015-01-01

    The effect of directly observed therapy (DOT) versus self-administered therapy (SAT) on antiretroviral (ART) adherence and virological outcomes in prison has never been assessed in a randomized, controlled trial. Prisoners were randomized to receive ART by DOT or SAT. The primary outcome was medication adherence [percent of ART doses measured by the medication event monitoring system (MEMS) and pill counts] at the end of 24 weeks. The changes in the plasma viral loads from baseline and proportion of participants virological suppressed (<400 copies/mL) at the end of 24 weeks were assessed. Sixty-six percent (90/136) of eligible prisoners declined participation. Participants in the DOT arm (n = 20) had higher viral loads than participants in the SAT (n = 23) arm (p = 0.23). Participants, with complete data at 24 weeks, were analyzed as randomized. There were no significant differences in median ART adherence between the DOT (n = 16, 99% MEMS [IQR 93.9, 100], 97.1 % pill count [IQR 95.1, 99.3]) and SAT (n = 21, 98.3 % MEMS [IQR 96.0, 100], 98.5 % pill count [95.8, 100]) arms (p = 0.82 MEMS, p = 0.40 Pill Count) at 24 weeks. Participants in the DOT arm had a greater reduction in viral load of approximately -1 log 10 copies/mL [IQR -1.75, -0.05] compared to -0.05 [IQR -0.45, 0.51] in the SAT arm (p value = 0.02) at 24 weeks. The proportion of participants achieving virological suppression in the DOT vs SAT arms was not statistically different at 24 weeks (53 % vs 32 %, p = 0.21). These findings suggest that DOT ART programs in prison settings may not offer any additional benefit on adherence than SAT programs. PMID:25055766

  4. Comparative Effectiveness of Initial Antiretroviral Therapy Regimens: ACTG 5095 and 5142 Clinical Trials Relative to ART-CC Cohort Study

    PubMed Central

    Mugavero, Michael J.; May, Margaret; Ribaudo, Heather J.; Gulick, Roy M.; Riddler, Sharon A.; Haubrich, Richard; Napravnik, Sonia; Abgrall, Sophie; Phillips, Andrew; Harris, Ross; Gill, M. John; de Wolf, Frank; Hogg, Robert; Günthard, Huldrych F.; Chêne, Geneviève; D'Arminio Monforte, Antonella; Guest, Jodie L.; Smith, Colette; Murillas, Javier; Berenguer, Juan; Wyen, Christoph; Domingo, Pere; Kitahata, Mari M.; Sterne, Jonathan A. C.; Saag, Michael S.

    2011-01-01

    Background The generalizability of antiretroviral therapy (ART) clinical trial efficacy findings to routine care settings is not well studied. We compared the relative effectiveness of initial ART regimens estimated in AIDS Clinical Trial Group (ACTG) randomized controlled trials with that among patients receiving ART at Antiretroviral Therapy Cohort Collaboration (ART-CC) study sites. Methods Treatment-naive HIV-infected patients initiating identical ART regimens in ACTG trials (A5095 and A5142) and at 15 ART-CC cohort study sites were included. Virological failure (HIV-1 RNA >200 copies/ml) at 24- and 48-weeks, incident AIDS-defining events and mortality were measured according to study design (ART-CC cohort vs. ACTG trial) and stratified by 3rd drug [Abacavir (ABC), Efavirenz (EFV), and Lopinavir/r (LPV/r)]. We used logistic regression to estimate and compare odds ratios for virological failure between different regimens and study designs, and used Cox models to estimate and compare hazard ratios for AIDS and death. Results Compared with patients receiving ABC, those receiving EFV had roughly half the odds of 24-week virologic failure (>200 copies/mL) in both ACTG 5095 (OR=0.53, 95% CI 0.36–0.79) and ART-CC (0.46, 0.37–0.57). Virologic superiority of EFV (vs. ABC) appeared comparable in ART-CC and ACTG 5095 (ratio of ORs 0.86, 95% CI 0.54–1.35). Odds ratios for 48-week virologic failure, comparing EFV with LPV/r, were also comparable in ACTG 5142 and ART-CC (ratio of ORs 0.87, 0.45–1.69). Conclusions Between ART regimen virologic efficacy of 3rd drugs ABC, EFV, and LPV/r observed in the ACTG 5095 and 5142 trials appear generalizable to the routine care setting of ART-CC clinical cohorts. PMID:21857357

  5. Superior Effectiveness of Zidovudine Compared With Tenofovir When Combined With Nevirapine-based Antiretroviral Therapy in a Large Nigerian Cohort

    PubMed Central

    Scarsi, Kimberly K.; Eisen, Geoffrey; Darin, Kristin M.; Meloni, Seema T.; Rawizza, Holly E.; Tchetgen Tchetgen, Eric J.; Agbaji, Oche O.; Onwujekwe, Daniel I.; Gashau, Wadzani; Nkado, Reuben; Okonkwo, Prosper; Murphy, Robert L.; Kanki, Phyllis J.

    2016-01-01

    Background. Despite sparse efficacy data, tenofovir–emtricitabine or tenofovir–lamivudine plus nevirapine is used in many resource-constrained settings. Methods. This retrospective cohort study included patients initiating nevirapine-based antiretroviral therapy (ART) with either tenofovir–emtricitabine or lamivudine (tenofovir group) or zidovudine–lamivudine (zidovudine group). Clinical, virologic, and immunologic evaluations were performed at baseline and every 6 months. Virologic failure was defined as 2 consecutive human immunodeficiency virus (HIV)-RNA values >1000 copies/mL. Patients were included from ART initiation until time of failure, regimen switch, discontinuation, or last HIV-RNA measurement. Cox proportional hazards regression was used to model factors influencing time to failure. Bias due to dependent censoring was investigated via inverse probability weighted pooled logistic regression. Results. A total of 5547 patients were evaluated; 1484 (26.8%) were in the tenofovir group and 4063 (73.2%) were in the zidovudine group. In the adjusted model, tenofovir regimen (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.21–1.79) and higher baseline log10 HIV-RNA (HR, 1.15; 95% CI, 1.03–1.28) were associated with virologic failure. Higher baseline log10 CD4+ cell count (HR, 0.50; 95% CI, .40–.63) and increasing age (HR, 0.98; 95% CI, .97–.99) decreased the risk of virologic failure. Inverse probability weighting results were consistent with the primary analysis. Conclusions. Compared with zidovudine–lamivudine, the use of tenofovir–lamivudine or emtricitabine in combination with nevirapine was a strong predictor of virologic failure in our cohort, which was not explained by other risk factors or criteria for regimen selection. PMID:26561532

  6. Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.

    PubMed

    Koethe, John R; Jenkins, Cathy A; Petucci, Christopher; Culver, Jeffrey; Shepherd, Bryan E; Sterling, Timothy R

    2016-05-01

    In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50 copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P < 0.05 for both) compared with men but had similar CD4+ count (median 701 cells/μL), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3 kg/m). However, women had higher insulin sensitivity compared with men (P < 0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P < 0.01 for all), and lower C3 and C5 acylcarnitines (P < 0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite levels did not

  7. Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy

    PubMed Central

    Koethe, John R.; Jenkins, Cathy A.; Petucci, Christopher; Culver, Jeffrey; Shepherd, Bryan E.; Sterling, Timothy R.

    2016-01-01

    Abstract In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART. We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50 copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism. HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P < 0.05 for both) compared with men but had similar CD4+ count (median 701 cells/μL), smoking and hepatic C prevalence, and body mass index (BMI) (median 30.3 kg/m2). However, women had higher insulin sensitivity compared with men (P < 0.01), and lower plasma levels of isoleucine, leucine, valine, phenylalanine, and tyrosine (P < 0.01 for all), and lower C3 and C5 acylcarnitines (P < 0.01 for all), in multivariable regression models after adjusting for DEXA fat mass index, age, race, CD4+ count, smoking, and ART duration. In the obese HIV-infected subjects and HIV-negative controls, the relationship of sex and plasma metabolite

  8. Thirty-Day Postoperative Mortality Among Individuals With HIV Infection Receiving Antiretroviral Therapy and Procedure-Matched, Uninfected Comparators

    PubMed Central

    King, Joseph T.; Perkal, Melissa F.; Rosenthal, Ronnie A.; Gordon, Adam J.; Crystal, Stephen; Rodriguez-Barradas, Maria C.; Butt, Adeel A.; Gibert, Cynthia L.; Rimland, David; Simberkoff, Michael S.; Justice, Amy C.

    2016-01-01

    IMPORTANCE Antiretroviral therapy (ART) has converted human immunodeficiency virus (HIV) infection into a chronic condition, and patients now undergo a variety of surgical procedures, but current surgical outcomes are inadequately characterized. OBJECTIVE To compare 30-day postoperative mortality in patients with HIV infection receiving ART with the rates in uninfected individuals. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of nationwide electronic medical record data from the US Veterans Health Administration Healthcare System, October 1, 1996, to September 30, 2010. Common inpatient surgical procedures were grouped using the Healthcare Cost and Utilization Project Clinical Classification System to match HIV-infected and uninfected patients in a 1:2 ratio. Data on 1641 patients with HIV infection receiving combination ART who were undergoing inpatient surgery were compared with data on 3282 procedure-matched, uninfected comparators. Poisson regression models of 30-day postoperative mortality were adjusted for procedure year, age, Charlson Comorbidity Index score, hemoglobin level, albumin level, HIV infection, CD4 cell count, and HIV-1 RNA level. MAIN OUTCOMES AND MEASURES All-cause 30-day postoperative mortality. RESULTS The most common procedures in both groups were cholecystectomy (10.5%), hip arthroplasty (10.5%), spine surgery (9.8%), herniorrhaphy (7.4%), and coronary artery bypass grafting (7.0%). In patients with HIV infection, CD4 cell distributions were 80.0% with 200/µL or more, 16.3% with 50/µL to 199/µL, and 3.7% with less than 50/µL; 74.1% of patients with HIV infection had undetectable HIV-1 RNA. Human immunodeficiency virus infection was associated with higher 30-day postoperative mortality compared with the mortality in uninfected patients (3.4% [56 patients]) vs 1.6% [53]); incidence rate ratio [IRR], 2.11; 95% CI, 1.41–3.17; P < .001). CD4 cell count was inversely associated with mortality, but HIV-1 RNA provided no

  9. HIV-1 antiretroviral drug therapy.

    PubMed

    Arts, Eric J; Hazuda, Daria J

    2012-04-01

    The most significant advance in the medical management of HIV-1 infection has been the treatment of patients with antiviral drugs, which can suppress HIV-1 replication to undetectable levels. The discovery of HIV-1 as the causative agent of AIDS together with an ever-increasing understanding of the virus replication cycle have been instrumental in this effort by providing researchers with the knowledge and tools required to prosecute drug discovery efforts focused on targeted inhibition with specific pharmacological agents. To date, an arsenal of 24 Food and Drug Administration (FDA)-approved drugs are available for treatment of HIV-1 infections. These drugs are distributed into six distinct classes based on their molecular mechanism and resistance profiles: (1) nucleoside-analog reverse transcriptase inhibitors (NNRTIs), (2) non-nucleoside reverse transcriptase inhibitors (NNRTIs), (3) integrase inhibitors, (4) protease inhibitors (PIs), (5) fusion inhibitors, and (6) coreceptor antagonists. In this article, we will review the basic principles of antiretroviral drug therapy, the mode of drug action, and the factors leading to treatment failure (i.e., drug resistance).

  10. Antiretroviral Therapy in the Clinic▿

    PubMed Central

    Tsibris, Athe M. N.; Hirsch, Martin S.

    2010-01-01

    Antiretroviral therapy in the developed world has resulted in substantial reductions in HIV-associated morbidity and mortality, changing an HIV diagnosis from a likely death sentence into a manageable chronic infection (F. J. Palella, Jr., K. M. Delaney, A. C. Moorman, M. O. Loveless, J. Fuhrer, G. A. Satten, D. J. Aschman, and S. D. Holmberg, N. Engl. J. Med. 338:853-860, 1998). Several million years of life have been saved by effective anti-HIV treatment, although these successes should not obscure the magnitude of the ongoing worldwide HIV epidemic (R. P. Walensky, A. D. Paltiel, E. Losina, L. M. Mercincavage, B. R. Schackman, P. E. Sax, M. C. Weinstein, and K. A. Freedberg, J. Infect. Dis. 194:11-19, 2006). Readers of the Journal of Virology are doubtless aware of the fundamental advances in retrovirology that have made possible the development of potent inhibitors of HIV replication. In this review, we focus on the issues surrounding how these drugs and drug regimens are actually used in clinical settings. Their proper use requires detailed knowledge of the natural history of HIV infection, the pharmacology of the individual drugs, the complexities of drug-drug interactions, and the use of sophisticated molecular tests for monitoring of viral load, immunologic response, and drug resistance. PMID:20181709

  11. Pharmacy Refill Adherence Compared with CD4 Count Changes for Monitoring HIV-Infected Adults on Antiretroviral Therapy

    PubMed Central

    Bisson, Gregory P; Gross, Robert; Bellamy, Scarlett; Chittams, Jesse; Hislop, Michael; Regensberg, Leon; Frank, Ian; Maartens, Gary; Nachega, Jean B

    2008-01-01

    Background World Health Organization (WHO) guidelines for monitoring HIV-infected individuals taking combination antiretroviral therapy (cART) in resource-limited settings recommend using CD4+ T cell (CD4) count changes to monitor treatment effectiveness. In practice, however, falling CD4 counts are a consequence, rather than a cause, of virologic failure. Adherence lapses precede virologic failure and, unlike CD4 counts, data on adherence are immediately available to all clinics dispensing cART. However, the accuracy of adherence assessments for predicting future or detecting current virologic failure has not been determined. The goal of this study therefore was to determine the accuracy of adherence assessments for predicting and detecting virologic failure and to compare the accuracy of adherence-based monitoring approaches with approaches monitoring CD4 count changes. Methodology and Findings We conducted an observational cohort study among 1,982 of 4,984 (40%) HIV-infected adults initiating non-nucleoside reverse transcriptase inhibitor-based cART in the Aid for AIDS Disease Management Program, which serves nine countries in southern Africa. Pharmacy refill adherence was calculated as the number of months of cART claims submitted divided by the number of complete months between cART initiation and the last refill prior to the endpoint of interest, expressed as a percentage. The main outcome measure was virologic failure defined as a viral load > 1,000 copies/ml (1) at an initial assessment either 6 or 12 mo after cART initiation and (2) after a previous undetectable (i.e., < 400 copies/ml) viral load (breakthrough viremia). Adherence levels outperformed CD4 count changes when used to detect current virologic failure in the first year after cART initiation (area under the receiver operating characteristic [ROC] curves [AUC] were 0.79 and 0.68 [difference = 0.11; 95% CI 0.06 to 0.16; χ2 = 20.1] respectively at 6 mo, and 0.85 and 0.75 [difference = 0.10; 95% CI

  12. Neuropathology of AIDS: An Autopsy Review of 284 Cases from Brazil Comparing the Findings Pre- and Post-HAART (Highly Active Antiretroviral Therapy) and Pre- and Postmortem Correlation

    PubMed Central

    Silva, Ana Cristina Araújo Lemos; Rodrigues, Blenda Sousa Carli; Micheletti, Adilha Misson Rua; Tostes, Sebastião; Meneses, Antonio Carlos Oliveira; Silva-Vergara, Mário Leon; Adad, Sheila Jorge

    2012-01-01

    A retrospective study of central nervous system (CNS) in 284 autopsy AIDS cases in Brazil (1989–2008) divided into 3 groups: A (without antiretroviral treatment: 163 cases); B (other antiretroviral therapies: 76 cases); C (HAART for 3 months or more: 45 cases). In 165 (58.1%) cases, relevant lesions were found, predominantly infections (54.2%); the most frequent was toxoplasmosis (29.9%) followed by cryptococcosis (15.8%), purulent bacterial infections (3.9%), and HIV encephalitis (2.8%); non-Hodgkin lymphomas occurred in 1.4% and vascular lesions in 1.1%. There was no difference when compared the frequency of lesion among the groups; however, toxoplasmosis was less common while HIV encephalitis was more frequent in group C related to A. CNS lesions remain a frequent cause of death in AIDS; however, the mean survival time was four times greater in group C than in A. In 91 (55.1%) of 165 cases with relevant brain lesions (or 32% of the total 284 cases), there was discordance between pre- and postmortem diagnosis; disagreement type 1 (important disease that if diagnosed in life could change the patient prognosis) occurred in 49 (53.8%) of 91 discordant cases (17.6% of the total 284) indicating the autopsy importance, even with HAART and advanced diagnostics technologies. PMID:22461978

  13. CROI 2016: Advances in Antiretroviral Therapy.

    PubMed

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID:27398863

  14. Response to antiretroviral therapy (ART): comparing women with previous use of zidovudine monotherapy (ZDVm) in pregnancy with ART naïve women

    PubMed Central

    2014-01-01

    Background Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. Methods Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis. Outcomes were compared using logistic regression, proportional hazards regression or linear regression. Results In adjusted analyses, ART-naïve (n = 1937) and ZDVm-experienced (n = 91) women had similar increases in CD4 count and a similar proportion achieving virological suppression; both groups had a low risk of AIDS. Conclusions In this setting, antenatal ZDVm exposure did not adversely impact on outcomes once ART was initiated for the woman’s health. PMID:24593018

  15. Individualization of antiretroviral therapy - Pharmacogenomic aspect

    PubMed Central

    Dalal, Bhavik; Shankarkumar, Aruna; Ghosh, K.

    2015-01-01

    Combination therapy with three drug regimens for human immunodeficiency virus (HIV) infection significantly suppresses the viral replication. However, this therapeutic impact is restricted by adverse drug events and response in terms of short and long term efficacy. There are multiple factors involved in different responses to antiretrovirals (ARVs) such as age, body weight, disease status, diet and heredity. Pharmacogenomics deals with individual genetic make-up and its role in drug efficacy and toxicity. In depth genetic research has provided evidence to predict the risk of developing certain toxicities for which personalized screening and surveillance protocols may be developed to prevent side effects. Here we describe the use of pharmacogenomics for optimal use of HAART (highly active antiretroviral therapy). PMID:26831415

  16. Challenges in initiating antiretroviral therapy in 2010.

    PubMed

    Tremblay, Cécile L; Baril, Jean-Guy; Fletcher, David; Kilby, Donald; Macpherson, Paul; Shafran, Stephen D; Tyndall, Mark W

    2010-08-01

    Many clinical trials have shown that initiating antiretroviral therapy (ART) at higher rather than lower CD4 T cell-positive counts results in survival benefit. Early treatment can help prevent end-organ damage associated with HIV replication and can decrease infectivity. The mainstay of treatment is either a non-nucleoside reverse transcriptase inhibitor or a ritonavir-boosted protease inhibitor in combination with two nucleoside reverse transcriptase inhibitors. While effective at combating HIV, ART can produce adverse alterations of lipid parameters, with some studies suggesting a relationship between some anti-retroviral agents and cardiovascular disease. As the HIV-positive population ages, issues such as hypertension and diabetes must be taken into account when initiating ART. Adhering to ART can be difficult; however, nonoptimal adherence to ART can result in the development of resistance; thus, drug characteristics and the patient's preparedness to begin therapy must be considered. Reducing the pill burden through the use of fixed-dose antiretroviral drug combinations can facilitate adherence.

  17. Adherence to Antiretroviral Therapy and Virologic Failure

    PubMed Central

    Bezabhe, Woldesellassie M.; Chalmers, Leanne; Bereznicki, Luke R.; Peterson, Gregory M.

    2016-01-01

    Abstract The often cited need to achieve ≥95% (nearly perfect) adherence to antiretroviral therapy (ART) for successful virologic outcomes in HIV may present a barrier to initiation of therapy in the early stages of HIV. This meta-analysis synthesized 43 studies (27,905 participants) performed across >26 countries, to determine the relationship between cut-off point for optimal adherence to ART and virologic outcomes. Meta-analysis was performed using a random-effect model to calculate pooled odds ratios with corresponding 95% confidence intervals. The mean rate of patients reporting optimal adherence was 63.4%. Compared with suboptimal adherence, optimal adherence was associated with a lower risk of virologic failure (0.34; 95% CI: 0.26–0.44). There were no significant differences in the pooled odds ratios among different optimal adherence thresholds (≥98–100%, ≥95%, ≥80–90%). Study design (randomized controlled trial vs observational study) (regression coefficient 0.74, 95% CI: 0.04–1.43, P < 0.05) and study region (developing vs developed countries; regression coefficient 0.56, 95% CI: 0.01–1.12, P < 0.05) remained as independent predictors of between-study heterogeneity, with more patients with optimal adherence from developing countries or randomized controlled trials experiencing virologic failure. The threshold for optimal adherence to achieve better virologic outcomes appears to be wider than the commonly used cut-off point (≥95% adherence). The cut-off point for optimal adherence could be redefined to a slightly lower level to encourage the prescribing ART at an early stage of HIV infection. PMID:27082595

  18. Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naïve subjects gives comparable immunogenicity to one dose in ART+ subjects.

    PubMed

    Dieye, Tandakha N; Ndiaye, Birahim P; Dieng, Alle B; Fall, Marema; Brittain, Nathaniel; Britain, Nathaniel; Vermaak, Samantha; Camara, Makhtar; Diop-Ndiaye, Halimatou; Ngom-Gueye, Ndeye Fatou; Diaw, Papa A; Toure-Kane, Coumba; Sow, Papa S; Mboup, Souleymane; McShane, Helen

    2013-01-01

    Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1∶12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100,000 copies/ml. Group 2∶12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, haematology and biochemistry. Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. There were no vaccine-related Serious Adverse Events (SAEs) or clinically significant effects on HIV RNA load or CD4 count. In ART naive subjects, the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation, which contracted to baseline by 12 weeks. Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects. Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects; responses were comparable after 2 immunisations. In conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal. A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART. Clinicaltrials.gov trial identifier NCT00731471.

  19. Comparative analysis of drug resistance mutations in the human immunodeficiency virus reverse transcriptase gene in patients who are non-responsive, responsive and naive to antiretroviral therapy.

    PubMed

    Misbah, Mohammad; Roy, Gaurav; Shahid, Mudassar; Nag, Nalin; Kumar, Suresh; Husain, Mohammad

    2016-05-01

    Drug resistance mutations in the Pol gene of human immunodeficiency virus 1 (HIV-1) are one of the critical factors associated with antiretroviral therapy (ART) failure in HIV-1 patients. The issue of resistance to reverse transcriptase inhibitors (RTIs) in HIV infection has not been adequately addressed in the Indian subcontinent. We compared HIV-1 reverse transcriptase (RT) gene sequences to identify mutations present in HIV-1 patients who were ART non-responders, ART responders and drug naive. Genotypic drug resistance testing was performed by sequencing a 655-bp region of the RT gene from 102 HIV-1 patients, consisting of 30 ART-non-responding, 35 ART-responding and 37 drug-naive patients. The Stanford HIV Resistance Database (HIVDBv 6.2), IAS-USA mutation list, ANRS_09/2012 algorithm, and Rega v8.02 algorithm were used to interpret the pattern of drug resistance. The majority of the sequences (96 %) belonged to subtype C, and a few of them (3.9 %) to subtype A1. The frequency of drug resistance mutations observed in ART-non-responding, ART-responding and drug-naive patients was 40.1 %, 10.7 % and 20.58 %, respectively. It was observed that in non-responders, multiple mutations were present in the same patient, while in responders, a single mutation was found. Some of the drug-naive patients had more than one mutation. Thymidine analogue mutations (TAMs), however, were found in non-responders and naive patients but not in responders. Although drug resistance mutations were widely distributed among ART non-responders, the presence of resistance mutations in the viruses of drug-naive patients poses a big concern in the absence of a genotyping resistance test. PMID:26801790

  20. Impact of earlier combination antiretroviral therapy on outcomes in children

    PubMed Central

    Cotton, Mark F.; Rabie, Helena

    2015-01-01

    Purpose of review Early initiation of combination antiretroviral therapy (ART) in infants below 12 weeks of age reduces morbidity and mortality. A recent report of transient HIV remission in a child beginning ART from the second day of life has focused attention on very early therapy in the first days of life. Recent findings In the randomized children with HIV, early antiretroviral limited ART beginning at a median of 7.4 weeks of age lowered mortality and disease progression significantly compared with deferred ART beginning at a median of 21 weeks on study. In high-burden settings, infants initiating ART appear sicker than in children with HIV early antiretroviral and start at a later age. Many could be diagnosed on the first day of life. There are still programmatic obstacles to early diagnosis and initiation of ART in high-burden settings. There is growing but insufficient information on ART dosages in newborn infants. Summary There is now increased focus on initiating ART as postexposure prophylaxis in newborn infants at high risk of vertical transmission in the hope of limiting morbidity and dissemination of the virus. PMID:25389804

  1. Outcomes of antiretroviral therapy in children in Asia and Africa: a comparative analysis of the IeDEA pediatric multiregional collaboration

    PubMed Central

    Leroy, Valeriane; Malateste, Karen; Rabie, Helena; Lumbiganon, Pagakrong; Ayaya, Samuel; Dicko, Fatoumata; Davies, Mary-Ann; Kariminia, Azar; Wools-Kaloustian, Kara; Aka, Edmond; Phiri, Samuel; Aurpibul, Linda; Yiannoutsos, Constantin; Signaté-Sy, Haby; Mofenson, Lynne; Dabis, François

    2013-01-01

    Background We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. Methods HIV-infected children (positive PCR <18 months or positive serology ≥18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). Findings Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. Conclusion Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level. PMID:23187940

  2. The Association of Adherence to Antiretroviral Therapy with Healthcare Utilization and Costs for Medical Care

    PubMed Central

    Gardner, Edward M.; Maravi, Moises E.; Rietmeijer, Cornelis; Davidson, Arthur J.; Burman, William J.

    2009-01-01

    Background The association between antiretroviral adherence, healthcare utilization and medical costs has not been well studied. Objective To examine the relationship of adherence to antiretroviral medications to healthcare utilization and healthcare costs. Methods A retrospective cohort study was conducted using data from 325 previously antiretroviral medication-naive HIV-infected individuals initiating first antiretroviral therapy from 1997 through 2003. The setting was an inner-city safety net hospital and HIV clinic in the US. Adherence was assessed using pharmacy refill data. The average wholesale price was used for prescription costs. Healthcare utilization data and medical costs were obtained from the hospital billing database, and differences according to quartile of adherence were compared using analysis of variance (ANOVA). Multivariate logistic regression was used to assess predictors of higher annual medical costs. Sensitivity analyses were used to examine alternative antiretroviral pricing schemes. The perspective was that of the healthcare provider, and costs were in year 2005 values. Results In 325 patients followed for a mean (± SD) 3.2 (1.9) years, better adherence was associated with lower healthcare utilization but higher total medical costs. Annual non-antiretroviral medical costs were $US7612 in the highest adherence quartile versus $US10 190 in the lowest adherence quartile. However, antiretroviral costs were significantly higher in the highest adherence quartile ($US17 513 vs $US8690), and therefore the total annual medical costs were also significantly higher in the highest versus lowest adherence quartile ($US25 125 vs $US18 880). In multivariate analysis, for every 10% increase in adherence, the odds of having annual medical costs in the highest versus lowest quartile increased by 87% (odds ratio 1.87; 95% CI 1.45, 2.40). In sensitivity analyses, very low antiretroviral prices (as seen in resource-limited settings) inverted this

  3. Literacy, education and adherence to antiretroviral therapy in The Gambia.

    PubMed

    Hegazi, A; Bailey, R L; Ahadzie, B; Alabi, A; Peterson, K

    2010-11-01

    We examined the relationship of patients' literacy and education to antiretroviral therapy (ART) adherence in an urban treatment centre in The Gambia. Information on education and literacy systematically collected before ART initiation was compared against selected adherence outcomes. Formally educated patients were significantly more likely to achieve virological suppression at both six and 12 months (87% vs. 67%, OR=3.13, P=0.03; 88% vs. 63%, OR=4.49, P=0.007, respectively). Literate patients had similar benefit at 12 months (OR=3.39 P=0.03), with improved virological outcomes associated with degree of literacy (P=0.003). A trend towards similar results was seen at 6 months for Koranically educated patients; however, this was no longer apparent at 12 months. No significant correlation was seen between socio-demographic characteristics and missed appointments. Our study suggests that literacy, formal education and possibly Koranic education may impact favourably on adherence to ART.

  4. Response to antiretroviral therapy in occult hepatitis B and HIV co-infection in West Africa.

    PubMed

    Chadwick, David; Stanley, Alastair; Sarfo, Stephen; Appiah, Lambert; Ankcorn, Michael; Foster, Geraldine; Schwab, Uli; Phillips, Richard; Geretti, Anna M

    2013-01-01

    This study evaluated the outcome of first-line antiretroviral therapy among 35 Ghanaians with occult HBV/HIV co-infection, comparing them over 2 years to 120 patients with HBsAg+ HBV/HIV co-infection and 230 patients without HBV co-infection. Increases in CD4 cell count and BMI were similar, whereas elevations of hepatic transaminases were more frequent in both the occult HBV and HBsAg+ patients. Occult HBV/HIV co-infection appears not to impact adversely on response to antiretroviral therapy in Ghana. PMID:22874516

  5. Antiretroviral Therapy for HIV Infection: When to Initiate Therapy, Which Regimen to Use, and How to Monitor Patients on Therapy.

    PubMed

    Johnson, Steven C

    Antiretroviral therapy is recommended for all patients with HIV infection. The benefit of immediate antiretroviral therapy was confirmed by results from the START (Strategic Timing of Antiretroviral Treatment) trial, which showed a 57% reduction in risk for the composite end point of AIDS-related events, serious non-AIDS-related events, or death from any cause with immediate treatment in antiretroviral therapy-naive participants with CD4+ cell counts above 500/µL. Other changes in HIV care include the widespread adoption of integrase strand transfer inhibitor-based regimens. Considerations regarding when to initiate antiretroviral therapy, which initial regimens to use, and appropriate monitoring of individuals taking antiretroviral therapy are discussed. This article summarizes an IAS-USA continuing education webinar presented by Steven C. Johnson, MD, in July 2015.

  6. Managed Problem Solving for Antiretroviral Therapy Adherence: A Randomized Trial

    PubMed Central

    Gross, Robert; Bellamy, Scarlett L.; Chapman, Jennifer; Han, Xiaoyan; O’Duor, Jacqueline; Palmer, Steven C.; Houts, Peter S.; Coyne, James C.; Strom, Brian L.

    2015-01-01

    Background Adherence to antiretroviral therapy is critical to successful treatment of HIV. Few interventions have been demonstrated to improve both adherence and virological outcomes. We sought to determine whether an intervention derived from problem solving theory, Managed Problem Solving (MAPS), would improve antiretroviral outcomes. Methods We conducted a randomized investigator blind trial of MAPS compared with usual care in HIV-1 infected individuals at three HIV clinics in Philadelphia, PA. Eligible patients had plasma HIV-1 viral loads >1000 copies/ml and were initiating or changing therapy. MAPS consists of four in-person and 12 telephone-based meetings with a trained interventionist, then monthly follow-up calls for a year. Primary outcome was medication adherence measured using electronic monitors, summarized as fraction of doses taken quarterly over one year. Secondary outcome was undetectable HIV viral load over one year. We assessed 218 for eligibility, with 190 eligible and 180 enrolled, 91 randomized to MAPS and 89 to usual care. 56 participants were lost to follow-up: 33 in MAPS and 23 in usual care. Results In primary intention-to-treat analyses, the odds of being in a higher adherence category was 1.78 (95% CI:1.07–2.96) times greater for MAPS than usual care. In secondary analyses, the odds of an undetectable viral load was 1.48 (95% CI: 0.94–2.31) times greater for MAPS than usual care. In as-treated analyses, the effect of MAPS was stronger for both outcomes. There was neither a difference by prior treatment status nor change in effect over time. Conclusions MAPS is an effective antiretroviral adherence intervention over the first year with a new regimen. It was equally effective at improving adherence in treatment experienced and naïve patients and did not lose effect over time. Implementation of MAPS should be strongly considered where resources are available. Trial Registration ClinicalTrials.gov, NCT00130273 PMID:23358784

  7. Choosing Initial Antiretroviral Therapy: Current Recommendations for Initial Therapy and Newer or Investigational Agents.

    PubMed

    Gulick, Roy M

    2015-01-01

    There is general consistency among US and European guidelines regarding the initiation of antiretroviral therapy for HIV-infected individuals. Recent and ongoing trials comparing regimens may lead to reevaluation of initial treatment choices. The choice of antiretroviral regimen will also likely be affected by development, evaluation, and availability of newer drugs. This article reviews currently recommended regimens and characteristics of selected current investigational drugs, including the nucleotide analogue reverse transcriptase inhibitor tenofovir alafenamide, the nonnucleoside reverse transcriptase inhibitor doravirine, the integrase strand transfer inhibitor cabotegravir, the HIV entry inhibitor BMS-663068, and the HIV maturation inhibitor BMS-955176. This article summarizes a presentation by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in March 2015 and September 2015. PMID:26713502

  8. Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

    PubMed Central

    Zehnacker, Laura; Abe, Emuri; Mathez, Dominique; Alvarez, Jean-Claude; Leibowitch, Jacques; Azoulay, Stéphane

    2014-01-01

    Study of plasma and intracellular concentrations of atazanavir, lopinavir, nevirapine, and efavirenz was conducted on 48 patients under short cycles of antiretroviral therapy. Intracellular concentrations (IC) were still measurable for all drugs after 85 h or 110 h drug intake despite the absence of drug in plasma for atazanavir and lopinavir. A linear relationship between plasma and intracellular efavirenz was observed. Further studies to fully understand the impact of IC in the intermittent antiviral treatment are required. PMID:25431661

  9. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples.

    PubMed

    Anglemyer, Andrew; Horvath, Tara; Rutherford, George

    2013-10-16

    CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.

  10. Predicting virological decay in patients starting combination antiretroviral therapy

    PubMed Central

    2016-01-01

    Objective: Model trajectories of viral load measurements from time of starting combination antiretroviral therapy (cART), and use the model to predict whether patients will achieve suppressed viral load (≤200 copies/ml) within 6-months of starting cART. Design: Prospective cohort study including HIV-positive adults (UK Collaborative HIV Cohort Study). Methods: Eligible patients were antiretroviral naive and started cART after 1997. Random effects models were used to estimate viral load trends. Patients were randomly selected to form a validation dataset with those remaining used to fit the model. We evaluated predictions of suppression using indices of diagnostic test performance. Results: Of 9562 eligible patients 6435 were used to fit the model and 3127 for validation. Mean log10 viral load trajectories declined rapidly during the first 2 weeks post-cART, moderately between 2 weeks and 3 months, and more slowly thereafter. Higher pretreatment viral load predicted steeper declines, whereas older age, white ethnicity, and boosted protease inhibitor/non-nucleoside reverse transcriptase inhibitors based cART-regimen predicted a steeper decline from 3 months onwards. Specificity of predictions and the diagnostic odds ratio substantially improved when predictions were based on viral load measurements up to the 4-month visit compared with the 2 or 3-month visits. Diagnostic performance improved when suppression was defined by two consecutive suppressed viral loads compared with one. Conclusions: Viral load measurements can be used to predict if a patient will be suppressed by 6-month post-cART. Graphical presentations of this information could help clinicians decide the optimum time to switch treatment regimen during the first months of cART. PMID:27124894

  11. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review.

    PubMed

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-08-12

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  12. Pharmacogenetics as a tool to tailor antiretroviral therapy: A review

    PubMed Central

    Aceti, Antonio; Gianserra, Laura; Lambiase, Lara; Pennica, Alfredo; Teti, Elisabetta

    2015-01-01

    Highly active antiretroviral therapy (HAART) has substantially changed human immunodeficiency virus (HIV) infection from an inexorably fatal condition into a chronic disease with a longer life expectancy. This means that HIV patients should receive antiretroviral drugs lifelong, and the problems concerning with a chronic treatment (tolerability, side effects, adherence to treatment) have now become dominant. In this context, strategies for the treatment personalization have taken a central role in optimizing the therapeutic response and prevention of adverse drug reactions. In this setting, the study of pharmacogenetics features could be a very useful tool in clinical practice; moreover, nowadays the study of genetic profiles allows optimizations in the therapeutic management of People Living With HIV (PLWH) through the use of test introduced into clinical practice and approved by international guidelines for the adverse effects prevention such as the genetic test HLA-B*5701 to detect hypersensitivity to Abacavir. For other tests further studies are needed: CYP2B6 516 G > T testing may be able to identify patients at higher risk of Central Nervous System side effects following standard dosing of Efavirenz, UGT1A1*28 testing before initiation of antiretroviral therapy containing Atazanavir may aid in identifying individuals at risk of hyperbilirubinaemia. Pharmacogenetics represents a ​​research area with great growth potential which may be useful to guide the rational use of antiretrovirals. PMID:26279982

  13. Antiretroviral therapy reduces neurodegeneration in human immunodeficiency virus infection

    PubMed Central

    Bryant, Alex K.; Ellis, Ronald J.; Umlauf, Anya; Gouaux, Ben; Soontornniyomkij, Virawudh; Letendre, Scott L.; Achim, Cristian L.; Masliah, Eliezer; Grant, Igor; Moore, David J.

    2015-01-01

    Objective To determine the effect of virally-suppressive antiretroviral therapy on cortical neurodegeneration and associated neurocognitive impairment. Design Retrospective, postmortem observational study. Methods Clinical neuropsychological and postmortem neuropathology data were analyzed in 90 human immunodeficiency virus-infected volunteers from the general community who had never undergone antiretroviral therapy (n=7, “naïve”) or who had undergone antiretroviral therapy and whose plasma viral load was detectable (n = 64 “unsuppressed”) or undetectable (n = 19, “suppressed”) at the last clinical visit prior to death. Subjects were predominately male (74/90, 82%) with a mean age of 44.7 years (SD 9.8). Cortical neurodegeneration was quantified by measuring microtubule-associated protein (MAP2) and synaptophysin (SYP) density in midfrontal cortex tissue sections. Results The suppressed group had higher SYP density than the naïve group (p = 0.007) and higher MAP2 density than the unsuppressed group (p = 0.04). The suppressed group had lower odds of human immunodeficiency virus-associated neurocognitive disorders than naïve (OR 0.07, p = 0.03). Higher SYP was associated with lower likelihood of human immunodeficiency virus-associated neurocognitive disorders in univariable (OR 0.8, p=0.03) and multivariable models after controlling for antiretroviral treatment and brain human immunodeficiency virus p24 protein levels (OR 0.72, p=0.01). Conclusions We conclude that virally suppressive antiretroviral treatment protects against cortical neurodegeneration. Further, we find evidence supporting the causal chain from treatment-mediated peripheral and central nervous system viral load suppression to reduced neurodegeneration and improved neurocognitive outcomes. PMID:25686681

  14. Cost-effectiveness of the once-daily efavirenz/emtricitabine/tenofovir tablet compared with the once-daily elvitegravir/cobicistat/emtricitabine/tenofovir tablet as first-line antiretroviral therapy in HIV-infected adults in the US

    PubMed Central

    Juday, Timothy; Correll, Todd; Anene, Ayanna; Broder, Michael S; Ortendahl, Jesse; Bentley, Tanya

    2013-01-01

    Background February 2013 US treatment guidelines recommend the once-daily tablet of efavirenz/emtricitabine/tenofovir (Atripla®) as a preferred regimen and the once-daily tablet of elvitegravir/cobicistat/emtricitabine/tenofovir (Stribild™) as an alternative regimen for first-line treatment of human immunodeficiency virus (HIV). This study assessed the clinical and economic trade-offs involved in using Atripla compared with Stribild as first-line antiretroviral therapy in HIV-infected US adults. Methods A Markov cohort model was developed to project lifetime health-related outcomes, costs, quality-adjusted life years (QALYs), and cost-effectiveness of Stribild compared with Atripla as first-line antiretroviral therapy in HIV-1-infected US patients. Patients progressed in 12-week cycles through second-line, third-line, and nonsuppressive therapies, acquired immune deficiency syndrome, and death. Baseline characteristics and first-line virologic suppression, change in CD4 count, and adverse effects (lipid, central nervous system, rash, renal) were based on 48-week clinical trial results. These results demonstrated equivalent virologic suppression between the two regimens. Point estimates for virologic suppression (favoring Stribild) were used in the base case, and equivalency was used in the scenario analysis. Published sources and expert opinion were used to estimate costs, utilities, risk of acquired immune deficiency syndrome, mortality, subsequent-line CD4 count, clinical efficacy, and adverse events. Costs were reported in 2012 US dollars. Sensitivity analyses were conducted to assess robustness of results. Results Compared with patients initiating Atripla, patients initiating Stribild were estimated to have higher lifetime costs. Stribild added 0.041 QALYs over a lifetime at an additional cost of $6,886, producing an incremental cost-effectiveness ratio of $166,287/QALY gained. Results were most sensitive to first-line response rates, product costs, and

  15. Comparative manufacture and cell-based delivery of antiretroviral nanoformulations

    PubMed Central

    Balkundi, Shantanu; Nowacek, Ari S; Veerubhotla, Ram S; Chen, Han; Martinez-Skinner, Andrea; Roy, Upal; Mosley, R Lee; Kanmogne, Georgette; Liu, Xinming; Kabanov, Alexander V; Bronich, Tatiana; McMillan, JoEllyn; Gendelman, Howard E

    2011-01-01

    Nanoformulations of crystalline indinavir, ritonavir, atazanavir, and efavirenz were manufactured by wet milling, homogenization or sonication with a variety of excipients. The chemical, biological, immune, virological, and toxicological properties of these formulations were compared using an established monocyte-derived macrophage scoring indicator system. Measurements of drug uptake, retention, release, and antiretroviral activity demonstrated differences amongst preparation methods. Interestingly, for drug cell targeting and antiretroviral responses the most significant difference among the particles was the drug itself. We posit that the choice of drug and formulation composition may ultimately affect clinical utility. PMID:22267924

  16. Viral dynamics model with CTL immune response incorporating antiretroviral therapy.

    PubMed

    Wang, Yan; Zhou, Yicang; Brauer, Fred; Heffernan, Jane M

    2013-10-01

    We present two HIV models that include the CTL immune response, antiretroviral therapy and a full logistic growth term for uninfected CD4+ T-cells. The difference between the two models lies in the inclusion or omission of a loss term in the free virus equation. We obtain critical conditions for the existence of one, two or three steady states, and analyze the stability of these steady states. Through numerical simulation we find substantial differences in the reproduction numbers and the behaviour at the infected steady state between the two models, for certain parameter sets. We explore the effect of varying the combination drug efficacy on model behaviour, and the possibility of reconstituting the CTL immune response through antiretroviral therapy. Furthermore, we employ Latin hypercube sampling to investigate the existence of multiple infected equilibria. PMID:22930342

  17. Atazanavir/ritonavir-based combination antiretroviral therapy for treatment of HIV-1 infection in adults

    PubMed Central

    Achenbach, Chad J; Darin, Kristin M; Murphy, Robert L; Katlama, Christine

    2011-01-01

    In the past 15 years, improvements in the management of HIV infection have dramatically reduced morbidity and mortality. Similarly, rapid advances in antiretroviral medications have resulted in the possibility of life-long therapy with simple and tolerable regimens. Protease inhibitors have been important medications in regimens of combination antiretroviral therapy for the treatment of HIV. One of the recommended and commonly used therapies in this class is once-daily-administered atazanavir, pharmacologically boosted with ritonavir (atazanavir/r). Clinical studies and practice have shown these drugs, in combination with other antiretroviral agents, to be potent, safe and easy to use in a variety of settings. Atazanavir/r has minimal short-term toxicity, including benign bilirubin elevation, and has less potential for long-term complications of hyperlipidemia and insulin resistance compared with other protease inhibitors. A high genetic barrier to resistance and a favorable resistance profile make it an excellent option for initial HIV treatment or as the first drug utilized in the protease inhibitors class. Atazanavir/r is also currently being studied in novel treatment strategies, including combinations with new classes of antiretrovirals to assess nucleoside reverse transcriptase inhibitor-sparing regimens. In this article we review atazanavir/r as a treatment for HIV infection and discuss the latest information on its pharmacology, efficacy and toxicity. PMID:21731578

  18. Real-time adherence monitoring for HIV antiretroviral therapy.

    PubMed

    Haberer, Jessica E; Kahane, Josh; Kigozi, Isaac; Emenyonu, Nneka; Hunt, Peter; Martin, Jeffrey; Bangsberg, David R

    2010-12-01

    Current adherence assessments typically detect missed doses long after they occur. Real-time, wireless monitoring strategies for antiretroviral therapy may provide novel opportunities to proactively prevent virologic rebound and treatment failure. Wisepill, a wireless pill container that transmits a cellular signal when opened, was pilot tested in ten Ugandan individuals for 6 months. Adherence levels measured by Wisepill, unannounced pill counts, and self-report were compared with each other, prior standard electronic monitoring, and HIV RNA. Wisepill data was initially limited by battery life and signal transmission interruptions. Following device improvements, continuous data was achieved with median (interquartile range) adherence levels of 93% (87-97%) by Wisepill, 100% (99-100%) by unannounced pill count, 100% (100-100%) by self-report, and 92% (79-98%) by prior standard electronic monitoring. Four individuals developed transient, low-level viremia. After overcoming technical challenges, real-time adherence monitoring is feasible for resource-limited settings and may detect suboptimal adherence prior to viral rebound.

  19. Timing of Antiretroviral Therapy for HIV-1 Infection and Tuberculosis

    PubMed Central

    Havlir, D. V.; Kendall, M. A.; Ive, P.; Kumwenda, J.; Swindells, S.; Qasba, S. S.; Luetkemeyer, A. F.; Hogg, E.; Rooney, J.; Wu, X.; Hosseinipour, M. C.; Lalloo, U.; Veloso, V. G.; Some, F. F.; Kumarasamy, N.; Padayatchi, N.; Santos, B. R.; Reid, S.; Hakim, J.; Mohapi, L.; Mugyenyi, P.; Sanchez, J.; Lama, J. R.; Pape, J. W.; Sattler, F. R.; Asmelash, A.; Moko, E.; Sawe, F.; Andersen, J.; Sanne, I.

    2012-01-01

    Background Antiretroviral therapy (ART) is indicated during tuberculosis (TB) treatment of patients infected with HIV-1, but the urgency to start ART at TB diagnosis for patients of varying levels of immune compromise is not known. Methods We conducted an open label, randomized study comparing immediate (within 2 weeks of TB treatment initiation) to early (8–12 weeks) ART among HIV-1 infected patients with CD4+ lymphocytes < 250/mm3 and suspected TB. The primary study endpoint was proportion of patients who survived without an AIDS-defining illness at 48 weeks. Results 809 patients with median baseline CD4+ lymphocytes of 77 cells/mm3 and HIV-1 RNA of 5.43 log10 copies/mL were enrolled. In the immediate arm, 12.9% of patients experienced an AIDS-defining illness or death by 48 weeks compared to 16.1% in the early arm (p=0.45; 95% confidence interval (CI) for difference: −1.8%, 8.1%). In patients with screening CD4+ lymphocytes <50 cells/mm3, 15.5% of patients on the immediate arm vs. 26.6% on early ART experienced an AIDS defining illness or death (p=0.02; difference CI: 1.5%, 20.5%). TB immune reconstitution inflammatory syndrome (IRIS) was more common with immediate ART (11% vs. 5%: p=0.002). Viral suppression at 48 weeks was 74% and did not differ between arms (p=0.38). Conclusion Overall, immediate ART did not reduce AIDS-defining illnesses and death compared to early ART. For persons with CD4+ lymphocytes < 50 cells/mm3, immediate ART had 42% less AIDS defining illnesses and death compared to early ART. (ClinicalTrial.gov number NCT00108862.) PMID:22010914

  20. Correlates of non-adherence to antiretroviral therapy in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam.

    PubMed

    Jordan, M R; Obeng-Aduasare, Y; Sheehan, H; Hong, S Y; Terrin, N; Duong, D V; Trung, N V; Wanke, C; Kinh, N V; Tang, A M

    2014-08-01

    The HIV epidemic in Vietnam is concentrated, with high prevalence estimates among injection drug users and commercial sex workers. Socio-demographics, substance use and clinical correlates of antiretroviral therapy non-adherence were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy for at least 6 months in Hanoi, Vietnam. All study participants were men with a mean age of 29.9 ± 4.9 years. The median duration on antiretroviral therapy was 16.2 ± 12.7 months; 83% reported 'very good' or 'perfect' adherence in the past 30 days on a subjective one-item Likert scale at time of study enrollment; 48% of participants reported drug use within the previous 6 months, with 22% reporting current drug use. Injection drug use with or without non-injection drug use in the past 6 months (95% C.I. 2.19, 1.30-3.69) and years on antiretroviral therapy (95% C.I. 1.43, 1.14-1.78) were correlated with suboptimal adherence. These findings support Vietnam's ongoing scale-up of harm reduction programmes for injection drug users and their integration with antiretroviral therapy delivery. Moreover, results highlight the need to identify and implement new ways to support high levels of antiretroviral therapy adherence as duration on antiretroviral therapy increases.

  1. METHADONE MAINTENANCE THERAPY PROMOTES INITIATION OF ANTIRETROVIRAL THERAPY AMONG INJECTION DRUG USERS

    PubMed Central

    Uhlmann, Sasha; Milloy, M-J; Kerr, Thomas; Zhang, Ruth; Guillemi, Silvia; Marsh, David; Hogg, Robert S.; Montaner, Julio S. G.; Wood, Evan

    2010-01-01

    Aims Despite proven benefits of antiretroviral therapy (ART), many HIV-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. Design We prospectively examined a cohort of opioid-using antiretroviral-naïve HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors independently associated with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Findings Between May 1996 and April 2008, 231 antiretroviral-naïve HIV-infected opioid using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 (95% confidence interval [CI]: 25.9–35.6) per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was independently associated with more rapid uptake of antiretroviral therapy (relative hazard = 1.62 [95% CI: 1.15–2.28]; p = 0.006). Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation (odds ratio = 1.49 [95% CI: 1.07–2.08]; p = 0.019). Conclusion These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may dramatically increase uptake of HIV treatment among this population. PMID:20331553

  2. Antiretroviral Therapy for Prevention of Human Immunodeficiency Virus Infection.

    PubMed

    Kalapila, Aley G; Marrazzo, Jeanne

    2016-07-01

    Human immunodeficiency virus (HIV) infection is considered a chronic medical condition. Several new drugs are available, including fixed-dose combination tablets, that have greatly simplified combination antiretroviral therapy (ART) regimens to treat HIV, while increasing the life-expectancy of infected individuals. In the last decade, multiple well-regarded studies have established the benefits of using ART in high-risk, HIV-negative persons to prevent HIV acquisition. The primary care provider must not only understand commonly encountered issues pertaining to ART, such as toxicities and drug interactions, but also needs to be aware of using ART for HIV prevention. PMID:27235622

  3. Integrating Cervical Cancer Screening with HIV Care in Cameroon: Comparative Risk Analysis of Cervical Disease in HIV-Infected Women Receiving Antiretroviral Therapy to Women in the General Population

    PubMed Central

    Bekolo, Cavin Epie; O’Bryan, Gillian; Tchago, François Edmond; Nangue, Charlette; Bekoule, Patrick Sylvestre; Kollo, Basile

    2016-01-01

    Background While the effect of highly active antiretroviral therapy (HAART) on natural history of cervical lesions remains controversial, resource limited countries need to understand the relevance of their own data to their settings. We compared the risk of cervical disease in HAART-experienced women with that in women in the general population of Cameroon. Methods A retrospective cross sectional survey of women aged 35 years and above, attending a voluntary screening campaign for cervical cancer at the Nkongsamba Regional Hospital in Cameroon between February and May 2014. Squamous intraepithelial lesions (SIL) were determined by Pap smear. Multiple logistic regression was used to compare the odds of SIL in women on HAART to women from the community with unknown HIV status. Results Included were 302 women of whom 131(43.4%) were HIV-infected and receiving HAART on the site while 171 (56.6%) were women from the community. Cervical disease was observed in 51(16.9%) persons of whom 15 (11.5%) cases in the HAART group and 36 (21.1%) cases in the general group (p = 0.027). After controlling for age and other covariates, women in the HAART group had a 67% reduction in the odds of cervical lesions compared with the community group [adjusted odd ratio (aOR) = 0.33, 95%CI: 0.15–0.73, p = 0.006). Conclusion HIV-infected women receiving HAART have a lower risk of cancer than women in the general population. This finding may not be attributed to HAART alone but to all the health benefits derived from receiving a comprehensive HIV care. PMID:26866371

  4. 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.

  5. Leptin expression in HIV-infected patients during antiretroviral therapy

    PubMed Central

    Tiliscan, Cătălin; Aramă, Victoria; Mihăilescu, Raluca; Munteanu, Daniela Ioana; Streinu-Cercel, Adrian; Ion, Daniela Adriana; Rădulescu, Mihaela Andreea; Popescu, Cristina; Lobodan, Alina Elena; Negru, Anca Ruxandra; Aramă, Ştefan Sorin

    2015-01-01

    Background Leptin is an adipokine with complex metabolic, neuroendocrine and immune functions. Our objective was to evaluate leptin serum levels in a cohort of Romanian HIV-infected patients undergoing antiretroviral therapy in relation to their immune-virological status, lipid and glucose metabolic abnormalities and the presence of metabolic syndrome (MS). Methods We enrolled consecutive non-diabetic HIV-infected patients aged 18 and over on stable cART for at least 6 months. Blood samples were tested for: leptin, CD4 T cells count, HIV viral load and lipid panel. Results A total of 90 HIV-infected patients were included in the study: 50 males (55.6%) with a mean age of 33.3 years and 40 females with a mean age of 30.4 years. Most patients (74.4%) had HIV viral load below the limit of detection and the median CD4 count for the cohort was 476 (410) cells/cmm. More than one third of the patients (41.1%) had hypoleptinemia. The prevalence of MS was 13.3%. Hypoleptinemia was significantly more frequent in men. In a subset of patients with undetectable HIV viral load, the median leptin value was 0.6 (6.07) ng/mL in patients with poor immune recovery (CD4 count ≤ 200/cmm) compared to 2 (3.07) ng/mL for those with better immune response (CD4 count > 200/cmm), without statistical significance. The median values of leptin were similar for persons with and without MS criteria. HDL-cholesterol values were positively correlated to leptin values in a linear regression model. Conclusion A significant proportion of patients in our study presented low levels of leptin; this finding was not associated with immune and virological parameters or the presence of MS. Hypoleptinemia was significantly correlated with lower levels of HDL-cholesterol, a key cardiovascular risk factor. PMID:26405677

  6. Prevalence of oral candidiasis in HIV/AIDS children in highly active antiretroviral therapy era. A literature analysis.

    PubMed

    Gaitán-Cepeda, Luis Alberto; Sánchez-Vargas, Octavio; Castillo, Nydia

    2015-08-01

    SummaryHighly active antiretroviral therapy has decreased the morbidity and mortality related to HIV infection, including oral opportunistic infections. This paper offers an analysis of the scientific literature on the epidemiological aspects of oral candidiasis in HIV-positive children in the combination antiretroviral therapy era. An electronic databases search was made covering the highly active antiretroviral therapy era (1998 onwards). The terms used were oral lesions, oral candidiasis and their combination with highly active antiretroviral therapy and HIV/AIDS children. The following data were collected from each paper: year and country in which the investigation was conducted, antiretroviral treatment, oral candidiasis prevalence and diagnostic parameters (clinical or microbiological). Prevalence of oral candidiasis varied from 2.9% in American HIV-positive children undergoing highly active antiretroviral therapy to 88% in Chilean HIV-positive children without antiretroviral therapy. With respect to geographical location and antiretroviral treatment, higher oral candidiasis prevalence in HIV-positive children on combination antiretroviral therapy/antiretroviral therapy was reported in African children (79.1%) followed by 45.9% reported in Hindu children. In HIV-positive Chilean children on no antiretroviral therapy, high oral candidiasis prevalence was reported (88%) followed by Nigerian children (80%). Oral candidiasis is still frequent in HIV-positive children in the highly active antiretroviral therapy era irrespective of geographical location, race and use of antiretroviral therapy.

  7. When to Start Antiretroviral Therapy in Resource-limited Settings

    PubMed Central

    Walensky, Rochelle P.; Wolf, Lindsey L.; Wood, Robin; Fofana, Mariam O.; Freedberg, Kenneth A.; Martinson, Neil A.; Paltiel, A. David; Anglaret, Xavier; Weinstein, Milton C.; Losina, Elena

    2011-01-01

    Background Results of international clinical trials assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective To inform HIV treatment decisions over the short- and long-term regarding the optimal CD4 threshold at which to initiate ART in South Africa, while awaiting “when to start” trial results. Design Cost-effectiveness analysis using a computer simulation model of HIV disease. Data Sources Published data from randomized trials and observational cohorts in South Africa. Target Population HIV-infected patients in South Africa. Time Horizon Five-year and lifetime. Perspective Modified societal. Interventions No treatment, initiate ART at CD4<250/μl, and initiate ART at CD4<350/μl. Outcome Measures Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis If 10-100% of HIV-infected patients are diagnosed and linked to care, initiating ART at CD4<350/μl would reduce severe opportunistic diseases by 22,000-221,000 and deaths by 25,000-253,000 during the next 5 years, compared to initiating ART at CD4<250/μl; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART strategy increased long-term survival by at least 7.9 years, with a mean per person life expectancy of 3.8 years for no ART and 12.5 years for ART at <350/μl. Compared to initiating ART at <250/μl, initiating ART at <350/μl had an incremental cost-effectiveness ratio of $1,200/year of life saved. Results of Sensitivity Analysis Initiating ART at CD4<350/μl remained cost-effective over the next 5 years even if the probability that the trial would demonstrate superiority to earlier therapy is as low as 17%. Limitations This model does not consider the possible benefits of ART initiation at CD4>350/μl nor reduced HIV transmission. Conclusions Earlier ART initiation in South Africa will likely reduce morbidity and mortality, improve long-term survival, and be very cost

  8. Interruption of antiretroviral therapy is associated with increased plasma cystatin C

    PubMed Central

    Mocroft, A; Wyatt, C; Szczech, L; Neuhaus, J; El-Sadr, W; Tracy, R; Kuller, L; Shlipak, M; Angus, B; Klinker, H; Ross, M

    2009-01-01

    Background Cystatin C has been proposed as an alternative marker of renal function. We sought to determine if participants randomized to episodic use of antiretroviral therapy guided by CD4+ count (drug conservation; DC) had altered cystatin C levels compared to those randomised to continuous antiretroviral therapy (viral suppression; VS) in the Strategies for Management of Antiretroviral Therapy Trial, and to identify factors associated with increased cystatin C. Methods Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the DC and VS groups respectively. Logistic regression was used to model the odds of ≥ 0.15 mg/dl increase in cystatin C (1 standard deviation [SD]) in the first month after randomisation, adjusting for demographic and clinical characteristics. Results At randomisation, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the DC and VS arms respectively (p=0.29). In the first month after randomisation, 21.8% and 10.6% had ≥0.15 mg/dl increase in cystatin C in the DC and VS arm respectively (p=0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomisation. After adjustment, participants in the VS arm had significantly reduced odds of ≥0.15 mg/dl increase in cystatin C in the first month (OR 0.42; 95% CI 0.23–0.74, p=0.0023). Conclusions These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function. PMID:19050388

  9. Antiretroviral Therapies in Women after Single-Dose Nevirapine Exposure

    PubMed Central

    Lockman, S.; Hughes, M.D.; McIntyre, J.; Zheng, Y.; Chipato, T.; Conradie, F.; Sawe, F.; Asmelash, A.; Hosseinipour, M.C.; Mohapi, L.; Stringer, E.; Mngqibisa, R.; Siika, A.; Atwine, D.; Hakim, J.; Shaffer, D.; Kanyama, C.; Wools-Kaloustian, K.; Salata, R.A.; Hogg, E.; Alston-Smith, B.; Walawander, A.; Purcelle-Smith, E.; Eshleman, S.; Rooney, J.; Rahim, S.; Mellors, J.W.; Schooley, R.T.; Currier, J.S.

    2010-01-01

    BACKGROUND Peripartum administration of single-dose nevirapine reduces mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus. METHODS In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or had not taken single-dose nevirapine at least 6 months before enrollment were randomly assigned to receive antiretroviral therapy with tenofovir–emtricitabine plus nevirapine or tenofovir-emtricitabine plus lopinavir boosted by a low dose of ritonavir. The primary end point was the time to confirmed virologic failure or death. RESULTS A total of 241 women who had been exposed to single-dose nevirapine began the study treatments (121 received nevirapine and 120 received ritonavir-boosted lopinavir). Significantly more women in the nevirapine group reached the primary end point than in the ritonavir-boosted lopinavir group (26% vs. 8%) (adjusted P = 0.001). Virologic failure occurred in 37 (28 in the nevirapine group and 9 in the ritonavir-boosted lopinavir group), and 5 died without prior virologic failure (4 in the nevirapine group and 1 in the ritonavir-boosted lopinavir group). The group differences appeared to decrease as the interval between single-dose nevirapine exposure and the start of antiretroviral therapy increased. Retrospective bulk sequencing of baseline plasma samples showed nevirapine resistance in 33 of 239 women tested (14%). Among 500 women without prior exposure to single-dose nevirapine, 34 of 249 in the nevirapine group (14%) and 36 of 251 in the ritonavir-boosted lopinavir group (14%) had virologic failure or died. CONCLUSIONS In women with prior exposure to peripartum single-dose nevirapine (but not in those without prior exposure), ritonavir-boosted lopinavir plus tenofovir–emtricitabine was superior to nevirapine plus tenofovir–emtricitabine for initial antiretroviral therapy. (Funded by the National

  10. Determinants of antiretroviral therapy coverage in Sub-Saharan Africa.

    PubMed

    Furuoka, Fumitaka; Hoque, Mohammad Zahirul

    2015-01-01

    Among 35 million people living with the human immunodeficiency virus (HIV) in 2013, only 37% had access to antiretroviral therapy (ART). Despite global concerted efforts to provide the universal access to the ART treatment, the ART coverage varies among countries and regions. At present, there is a lack of systematic empirical analyses on factors that determine the ART coverage. Therefore, the current study aimed to identify the determinants of the ART coverage in 41 countries in Sub-Saharan Africa. It employed statistical analyses for this purpose. Four elements, namely, the HIV prevalence, the level of national income, the level of medical expenditure and the number of nurses, were hypothesised to determine the ART coverage. The findings revealed that among the four proposed determinants only the HIV prevalence had a statistically significant impact on the ART coverage. In other words, the HIV prevalence was the sole determinant of the ART coverage in Sub-Saharan Africa. PMID:26664812

  11. Determinants of antiretroviral therapy coverage in Sub-Saharan Africa

    PubMed Central

    Hoque, Mohammad Zahirul

    2015-01-01

    Among 35 million people living with the human immunodeficiency virus (HIV) in 2013, only 37% had access to antiretroviral therapy (ART). Despite global concerted efforts to provide the universal access to the ART treatment, the ART coverage varies among countries and regions. At present, there is a lack of systematic empirical analyses on factors that determine the ART coverage. Therefore, the current study aimed to identify the determinants of the ART coverage in 41 countries in Sub-Saharan Africa. It employed statistical analyses for this purpose. Four elements, namely, the HIV prevalence, the level of national income, the level of medical expenditure and the number of nurses, were hypothesised to determine the ART coverage. The findings revealed that among the four proposed determinants only the HIV prevalence had a statistically significant impact on the ART coverage. In other words, the HIV prevalence was the sole determinant of the ART coverage in Sub-Saharan Africa. PMID:26664812

  12. What Time is it? Adherence to Antiretroviral Therapy in Ethiopia

    PubMed Central

    Tiruneh, Yordanos M.; Wilson, Ira B.

    2016-01-01

    This study assessed adherence to antiretroviral therapy (ART) among people living with HIV/AIDS in Ethiopia and explored the sociocultural context in which they relate to their regimen requirements. Data were collected through semi-structured in-depth interviews with 105 patients on ART and observations held at the study clinic. We analyzed data using both qualitative and quantitative methods. Our findings indicate that study participants are highly adherent to dose but less adherent to dose schedule. Strict dose time instructions were reported as stressful and unrealistic. The discrepancy between adherence to dose and dose schedule could be explained by time perception, difficulty with the strictness of medication regimens, or beliefs about dose timing adherence. Care providers should acknowledge the complexities of medication practices and engage in shared decision-making to incorporate patients’ perspectives and identify effective interventions. PMID:26873491

  13. African Mitochondrial DNA Subhaplogroups and Peripheral Neuropathy during Antiretroviral Therapy

    PubMed Central

    Canter, Jeffrey A.; Robbins, Gregory K.; Selph, Doug; Clifford, David B.; Kallianpur, Asha R.; Shafer, Robert; Levy, Shawn; Murdock, Deborah G.; Ritchie, Marylyn D.; Haas, David W.; Hulgan, Todd

    2010-01-01

    Susceptibility to peripheral neuropathy during antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs) was previously associated with a European mitochondrial DNA (mtDNA) haplogroup among non-Hispanic white persons. To determine if NRTI-associated peripheral neuropathy was related to mtDNA variation in non-Hispanic black persons, we sequenced mtDNA of participants from AIDS Clinical Trials Group study 384. Of 156 non-Hispanic blacks with genomic data, 51 (33%) developed peripheral neuropathy. In a multivariate model, African mtDNA subhaplogroup L1c was an independent predictor of peripheral neuropathy (OR=3.7, 95% CI 1.1-12.0). An African mtDNA subhaplogroup is for the first time implicated in susceptibility to NRTI-associated toxicity. PMID:20402593

  14. Antiretroviral Therapy Initiation Following Policy Changes: Observations From China

    PubMed Central

    Li, Li; Ji, Guoping; Lin, Chunqing; Liang, Li-Jung; Lan, Chiao-Wen

    2016-01-01

    China’s HIV/AIDS treatment policies have been evolving over the preceding decade. This study describes patterns of antiretroviral therapy (ART) initiation for a sample of people living with HIV/AIDS (PLHIV) in rural Anhui, China, where most PLHIV were infected via paid plasma donation during the 1990s. A total of 481 PLHIV who were receiving ART were included in our analyses. Times between HIV diagnosis and the initiation of ART were examined relative to the time points when major ART-related policies changed in China. More than half (53%) of PLHIV who had been diagnosed by 2003 received ART within 6 months, whereas 93% of PLHIV who had been diagnosed in 2010 or later received ART within 6 months. The study results provide additional support that the “Four Frees and One Care” policy in 2003 and the relaxation of ART eligibility in 2010 have facilitated the initiation of treatment for PLHIV in China. PMID:27217427

  15. Outcomes of Universal Access to Antiretroviral Therapy (ART) in Georgia.

    PubMed

    Tsertsvadze, Tengiz; Chkhartishvili, Nikoloz; Sharvadze, Lali; Dvali, Natia; Chokoshvili, Otar; Gabunia, Pati; Abutidze, Akaki; Nelson, Kenrad; Dehovitz, Jack; Del Rio, Carlos

    2011-01-01

    Since 2004, Georgia achieved universal access to free antiretroviral therapy (ART). A retrospective cohort study was conducted to evaluate the outcomes of Georgia's ART program. The study included adult patients enrolled in the ART program from 2004 through 2009. Of 752 patients, 76% were men, 60% were injection drug users (IDU), 59% had a history of an AIDS-defining illness, and 53% were coinfected with hepatitis C. The median baseline CD4 cell count was 141 cells/mm(3). During followup, 152 (20%) patients died, with the majority of deaths occurring within 12 months of ART initiation. Mortality was associated with advanced immunodeficiency or the presence of incurable disease at baseline. Among patients remaining on treatment, the median CD4 gain was 216 cell/mm(3) and 86% of patients had viral load <400 copies/ml at the last clinical visit. The Georgia ART program has been successful in treating injection drug users infected with HIV.

  16. Comparisons of anemia, thrombocytopenia, and neutropenia at initiation of HIV antiretroviral therapy in Africa, Asia, and the Americas

    PubMed Central

    Firnhaber, Cynthia; Smeaton, Laura; Saukila, Nasinuku; Flanigan, Timothy; Gangakhedkar, Raman; Kumwenda, Johnstone; La Rosa, Alberto; Kumarasamy, Nagalingeswaran; De Gruttola, Victor; Hakim, James Gita; Campbell, Thomas B.

    2010-01-01

    Summary Background Hematological abnormalities are common manifestations of advanced HIV-1 infection that could affect the outcomes of highly-active antiretroviral therapy (HAART). Although most HIV-1-infected individuals live in resource-constrained countries, there is little information about the frequency of hematological abnormalities such as anemia, neutropenia, and thrombocytopenia among individuals with advanced HIV-1 disease. Methods This study compared the prevalence of pre-antiretroviral therapy hematological abnormalities among 1571 participants in a randomized trial of antiretroviral efficacy in Africa, Asia, South America, the Caribbean, and the USA. Potential covariates for anemia, neutropenia, and thrombocytopenia were identified in univariate analyses and evaluated in separate multivariable models for each hematological condition. Results The frequencies of neutropenia (absolute neutrophil count ≤ 1.3 × 109/l), anemia (hemoglobin ≤ 10 g/dl), and thrombocytopenia (platelets ≤ 125 × 109/l) at initiation of antiretroviral therapy were 14%, 12%, and 7%, respectively, and varied by country (p < 0.0001 for each). In multivariable models, anemia was associated with gender, platelet count, and country; neutropenia was associated with CD4+ lymphocyte and platelet counts; and thrombocytopenia was associated with country, gender, and chronic hepatitis B infection. Conclusions Differences in the frequency of pretreatment hematological abnormalities could have important implications for the choice of antiretroviral regimen in resource-constrained settings. PMID:20961784

  17. Cohort Profile: Antiretroviral Therapy Cohort Collaboration (ART-CC)

    PubMed Central

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D’Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan AC

    2014-01-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70 000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org). PMID:23599235

  18. Use of Third Line Antiretroviral Therapy in Latin America

    PubMed Central

    Cesar, Carina; Shepherd, Bryan E.; Jenkins, Cathy A.; Ghidinelli, Massimo; Castro, Jose Luis; Veloso, Valdiléa Gonçalves; Cortes, Claudia P.; Padgett, Denis; Crabtree-Ramirez, Brenda; Gotuzzo, Eduardo; Fink, Valeria; Duran, Adriana; Sued, Omar; McGowan, Catherine C.; Cahn, Pedro

    2014-01-01

    Background Access to highly active antiretroviral therapy (HAART) is expanding in Latin America. Many patients require second and third line therapy due to toxicity, tolerability, failure, or a combination of factors. The need for third line HAART, essential for program planning, is not known. Methods Antiretroviral-naïve patients ≥18 years who started first HAART after January 1, 2000 in Caribbean, Central and South America Network (CCASAnet) sites in Argentina, Brazil, Honduras, Mexico, and Peru were included. Clinical trials participants were excluded. Third line HAART was defined as use of darunavir, tipranavir, etravirine, enfuvirtide, maraviroc or raltegravir. Need for third line HAART was defined as virologic failure while on second line HAART. Results Of 5853 HAART initiators followed for a median of 3.5 years, 310 (5.3%) failed a second line regimen and 44 (0.8%) received a third line regimen. Cumulative incidence of failing a 2nd or starting a 3rd line regimen was 2.7% and 6.0% three and five years after HAART initiation, respectively. Predictors at HAART initiation for failing a second or starting a third line included female sex (hazard ratio [HR] = 1.54, 95% confidence interval [CI] 1.18–2.00, p = 0.001), younger age (HR = 2.76 for 20 vs. 40 years, 95% CI 1.86–4.10, p<0.001), and prior AIDS (HR = 2.17, 95% CI 1.62–2.90, p<0.001). Conclusions Third line regimens may be needed for at least 6% of patients in Latin America within 5 years of starting HAART, a substantial proportion given the large numbers of patients on HAART in the region. Improved accessibility to third line regimens is warranted. PMID:25221931

  19. Cohort profile: Antiretroviral Therapy Cohort Collaboration (ART-CC).

    PubMed

    May, Margaret T; Ingle, Suzanne M; Costagliola, Dominique; Justice, Amy C; de Wolf, Frank; Cavassini, Matthias; D'Arminio Monforte, Antonella; Casabona, Jordi; Hogg, Robert S; Mocroft, Amanda; Lampe, Fiona C; Dabis, François; Fätkenheuer, Gerd; Sterling, Timothy R; del Amo, Julia; Gill, M John; Crane, Heidi M; Saag, Michael S; Guest, Jodie; Brodt, Hans-Reinhard; Sterne, Jonathan A C

    2014-06-01

    The advent of effective combination antiretroviral therapy (ART) in 1996 resulted in fewer patients experiencing clinical events, so that some prognostic analyses of individual cohort studies of human immunodeficiency virus-infected individuals had low statistical power. Because of this, the Antiretroviral Therapy Cohort Collaboration (ART-CC) of HIV cohort studies in Europe and North America was established in 2000, with the aim of studying the prognosis for clinical events in acquired immune deficiency syndrome (AIDS) and the mortality of adult patients treated for HIV-1 infection. In 2002, the ART-CC collected data on more than 12,000 patients in 13 cohorts who had begun combination ART between 1995 and 2001. Subsequent updates took place in 2004, 2006, 2008, and 2010. The ART-CC data base now includes data on more than 70,000 patients participating in 19 cohorts who began treatment before the end of 2009. Data are collected on patient demographics (e.g. sex, age, assumed transmission group, race/ethnicity, geographical origin), HIV biomarkers (e.g. CD4 cell count, plasma viral load of HIV-1), ART regimen, dates and types of AIDS events, and dates and causes of death. In recent years, additional data on co-infections such as hepatitis C; risk factors such as smoking, alcohol and drug use; non-HIV biomarkers such as haemoglobin and liver enzymes; and adherence to ART have been collected whenever available. The data remain the property of the contributing cohorts, whose representatives manage the ART-CC via the steering committee of the Collaboration. External collaboration is welcomed. Details of contacts are given on the ART-CC website (www.art-cohort-collaboration.org).

  20. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies

    PubMed Central

    2011-01-01

    Summary Background Combination antiretroviral therapy has led to significant increases in survival and quality of life, but at a population-level the effect on life expectancy is not well understood. Our objective was to compare changes in mortality and life expectancy among HIV-positive individuals on combination antiretroviral therapy. Methods The Antiretroviral Therapy Cohort Collaboration is a multinational collaboration of HIV cohort studies in Europe and North America. Patients were included in this analysis if they were aged 16 years or over and antiretroviral-naive when initiating combination therapy. We constructed abridged life tables to estimate life expectancies for individuals on combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, stratified by sex, baseline CD4 cell count, and history of injecting drug use. The average number of years remaining to be lived by those treated with combination antiretroviral therapy at 20 and 35 years of age was estimated. Potential years of life lost from 20 to 64 years of age and crude death rates were also calculated. Findings 18 587, 13 914, and 10 854 eligible patients initiated combination antiretroviral therapy in 1996–99, 2000–02, and 2003–05, respectively. 2056 (4·7%) deaths were observed during the study period, with crude death rates decreasing from 16·3 deaths per 1000 person-years in 1996–99 to 10·0 deaths per 1000 person-years in 2003–05. Potential years of life lost per 1000 person-years also decreased over the same time, from 366 to 189 years. Life expectancy at age 20 years increased from 36·1 (SE 0·6) years to 49·4 (0·5) years. Women had higher life expectancies than men. Patients with presumed transmission via injecting drug use had lower life expectancies than those from other transmission groups (32·6 [1·1] years vs 44·7 [0·3] years in 2003–05). Life expectancy was lower in patients with lower baseline CD4 counts than in those with higher baseline counts

  1. Artemether-Lumefantrine Exposure in HIV-Infected Nigerian Subjects on Nevirapine-Containing Antiretroviral Therapy.

    PubMed

    Parikh, Sunil; Fehintola, Fatai; Huang, Liusheng; Olson, Alexander; Adedeji, Waheed A; Darin, Kristin M; Morse, Gene D; Murphy, Robert L; Taiwo, Babafemi O; Akinyinka, Olusegun O; Adewole, Isaac F; Aweeka, Francesca T; Scarsi, Kimberly K

    2015-12-01

    Coadministration of nevirapine-based antiretroviral therapy (ART) and artemether-lumefantrine is reported to result in variable changes in lumefantrine exposure. We conducted an intensive pharmacokinetic study with 11 HIV-infected adults who were receiving artemether-lumefantrine plus nevirapine-based ART, and we compared the results with those for 16 HIV-negative adult historical controls. Exposure to artemether and lumefantrine was significantly lower and dihydroartemisinin exposure was unchanged in subjects receiving nevirapine-based ART, compared with controls. Nevirapine exposure was unchanged before and after artemether-lumefantrine administration. PMID:26392500

  2. Oropharyngeal Candidiasis in the Era of Antiretroviral Therapy

    PubMed Central

    Thompson, George R.; Patel, Payal K.; Kirkpatrick, William R.; Westbrook, Steven D.; Berg, Deborah; Erlandsen, Josh; Redding, Spencer W.; Patterson, Thomas F.

    2009-01-01

    Oropharyngeal candidiasis (OPC) remains a common problem in the HIV-infected population despite the availability of antiretroviral therapy (ART). Although Candida albicans is the most frequently implicated pathogen, other Candida spp. may also cause infection. The emergence of antifungal resistance within these causative yeasts, especially in patients with recurrent oropharyngeal infection or with long-term use of antifungal therapies, requires a working knowledge of alternative antifungal agents. Identification of the infecting organism and antifungal susceptibility testing enhances the ability of clinicians to prescribe appropriate antifungal therapy. Characterization of the responsible mechanisms has improved our understanding of the development of antifungal resistance and could enhance the management of these infections. Immune reconstitution has been shown to reduce rates of oropharyngeal candidiasis but few studies have evaluated the current impact of ART on the epidemiology of oropharyngeal candidiasis and antifungal resistance in these patients. Preliminary results from an ongoing clinical study showed that in patients with advanced AIDS oral yeast colonization was extensive, occurring in 81.1% of the 122 patients studied and symptomatic infection occurred in a third. In addition, resistant yeasts were still common occurring in 25.3% of patients colonized with yeasts or with symptomatic infection. Thus, oropharyngeal candidasis remains a significant infection in advanced AIDS even with ART. Current knowledge of the epidemiology, pathogenesis, clinical presentation, treatment, and mechanisms of antifungal resistance observed in oropharyngeal candidiasis are important in managing patients with this infection and are the focus of this review. PMID:20156694

  3. Long-term immune responses and comparative effectiveness of one or two doses of 7-valent pneumococcal conjugate vaccine (PCV7) in HIV-positive adults in the era of combination antiretroviral therapy

    PubMed Central

    Cheng, Aristine; Chang, Sui-Yuan; Tsai, Mao-Song; Su, Yi-Ching; Liu, Wen-Chun; Sun, Hsin-Yun; Hung, Chien-Ching

    2016-01-01

    Introduction HIV infection impairs maintenance of immunological memory, yet few studies of HIV-positive adults receiving 7-valent pneumococcal conjugate vaccine (PCV7) have followed them beyond the first year. We determined and compared the durability of serological responses and the clinical outcomes of HIV-positive adults annually for five years following vaccination with one or two doses of PCV7. Methods In this non-randomized clinical trial, 221 pneumococcal vaccine-naïve HIV-positive adults receiving one (n=109) or two doses four weeks apart (n=112) of PCV7 between 2008 and 2010 were longitudinally followed for evaluation of significant serological response and for episodes of pneumonia and invasive pneumococcal disease. Results At the time of vaccination, the two groups were well matched for age, risk factors, combination antiretroviral therapy (cART) coverage, CD4 count and plasma HIV RNA load (PVL). At the end of five years, the CD4 counts for the one- and two-dose groups had increased from 407 and 406 to 550 and 592 cells/µL, respectively, and 82.4 and 81.6% of the participants had fully suppressed PVL. Significant immune responses to ≥2 serotypes persisted for 67.9 vs 78.6%, 64.2 vs 71.4%, 66.1 vs 71.4%, 57.8 vs 69.6% in the second, third, fourth and fifth years after one and two doses of PCV7 in the intention-to-treat analysis, respectively. In multivariate analysis, immunization with two doses of PCV7 (odds ratio (OR) 1.71, 95% confidence interval (CI) 1.10 to 2.65, p=0.016), concurrent cART (OR 2.16, 95% CI 1.16 to 4.00, p=0.015) and CD4 proliferation (OR 1.12, 95% CI 1.01 to 1.27, p=0.031) were predictive of persistent serological responses in the fifth year. Only one patient in the one-dose group had documented pneumococcal pneumonia (non-bacteraemic) and none had invasive pneumococcal disease in the 6.5 years of follow-up. Conclusions One or two doses of PCV7 achieve durable seroprotective responses in HIV-treated participants; however, two

  4. Treatment of HIV in the CNS: effects of antiretroviral therapy and the promise of non-antiretroviral therapeutics.

    PubMed

    Peluso, Michael J; Spudich, Serena

    2014-09-01

    The growing recognition of the burden of neurologic disease associated with HIV infection in the last decade has led to renewed efforts to characterize the pathophysiology of the virus within the central nervous system (CNS). The concept of the AIDS-dementia complex is now better understood as a spectrum of HIV-associated neurocognitive disorders (HAND), which range from asymptomatic disease to severe impairment. Recent work has shown that even optimally treated patients can experience not only persistent HAND, but also the development of new neurologic abnormalities despite viral suppression. This has thrown into question what the impact of antiretroviral therapy has been on the incidence and prevalence of neurocognitive dysfunction. In this context, the last few years have seen a concentrated effort to identify the effects that antiretroviral therapy has on the neurologic manifestations of HIV and to develop therapeutic modalities that might specifically alter the trajectory of HIV within the CNS.

  5. Infant peripheral blood repetitive element hypomethylation associated with antiretroviral therapy in utero

    PubMed Central

    Marsit, Carmen J; Brummel, Sean S; Kacanek, Deborah; Seage, George R; Spector, Stephen A; Armstrong, David A; Lester, Barry M; Rich, Kenneth

    2015-01-01

    The use of combination antiretroviral therapy (cART) to prevent HIV mother-to-child transmission during pregnancy and delivery is generally considered safe. However, vigilant assessment of potential risks of these agents remains warranted. Epigenetic changes including DNA methylation are considered potential mechanisms linking the in utero environment with long-term health outcomes. Few studies have examined the epigenetic effects of prenatal exposure to pharmaceutical agents, including antiretroviral therapies, on children. In this study, we examined the methylation status of the LINE-1 and ALU-Yb8 repetitive elements as markers of global DNA methylation alteration in peripheral blood mononuclear cells obtained from newborns participating in the Pediatric HIV/AIDS Cohort Study SMARTT cohort of HIV-exposed, cART-exposed uninfected infants compared to a historical cohort of HIV-exposed, antiretroviral-unexposed infants from the Women and Infants Transmission Study Cohort. In linear regression models controlling for potential confounders, we found the adjusted mean difference of AluYb8 methylation of the cART-exposed compared to the -unexposed was −0.568 (95% CI: −1.023, −0.149) and for LINE-1 methylation was −1.359 (95% CI: −1.860, −0.857). Among those exposed to cART, subjects treated with atazanavir (ATV), compared to those on other treatments, had less AluYb8 methylation (−0.524, 95% CI: −0.025, −1.024). Overall, these results suggest a small but statistically significant reduction in the methylation of these repetitive elements in an HIV-exposed, cART-exposed cohort compared to an HIV-exposed, cART-unexposed historic cohort. The potential long-term implications of these differences are worthy of further examination. PMID:26067216

  6. Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

    PubMed

    Fowler, Mary G; Qin, Min; Fiscus, Susan A; Currier, Judith S; Flynn, Patricia M; Chipato, Tsungai; McIntyre, James; Gnanashanmugam, Devasena; Siberry, George K; Coletti, Anne S; Taha, Taha E; Klingman, Karin L; Martinson, Francis E; Owor, Maxensia; Violari, Avy; Moodley, Dhayendre; Theron, Gerhard B; Bhosale, Ramesh; Bobat, Raziya; Chi, Benjamin H; Strehlau, Renate; Mlay, Pendo; Loftis, Amy J; Browning, Renee; Fenton, Terence; Purdue, Lynette; Basar, Michael; Shapiro, David E; Mofenson, Lynne M

    2016-11-01

    Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. Results The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated

  7. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

  8. Comparative effectiveness of efavirenz-based antiretroviral regimens in resource-limited settings

    PubMed Central

    Castillo-Mancilla, Jose R; Campbell, Thomas B

    2012-01-01

    Efavirenz (EFV) is a non-nucleoside widely used as first-line therapy for HIV-1 infection. Most of the research available on EFV comes from trials performed in industrialized countries and only a few studies have evaluated EFV in resource-limited settings (RLSs). In this article, we present a systematic review of the available randomized-controlled trials performed in RLSs that have compared EFV with other antiretrovirals, such as nevirapine and protease inhibitors. The data derived from these studies show that both EFV and nevirapine are adequate first-line therapy options for HIV-1 infection in RLSs, even in patients with concomitant tuberculosis. However, EFV may show a slight benefit in terms of toxicity and adverse events. By contrast, the data comparing EFV versus protease inhibitors is contradictory and further studies may be required to elucidate these discrepancies. PMID:22707879

  9. A Mathematical Model of Antiretroviral Therapy Evaluation for HIV Type 1

    NASA Astrophysics Data System (ADS)

    Raimundo, Silvia Martorano; Venturino, Ezio; Mo Yang, Hyun

    2009-09-01

    Treating HIV-infected patients with a combination of several antiretroviral drugs can lead to emergence of the drug-resistant strain. This work proposes a mathematical model to evaluate the emergence of HIV-1 drug resistant during antiretroviral therapy. The model assumes that all susceptible individuals who can be infected by the wildtype strain (sensible to the treatment) or by drug-resistant virus receive antiretroviral therapy. Patients on treatment regimen can evolve to a state of success or failure and for the individuals in therapeutic fail the therapeutic schema is changed. The analysis of system is performed. The existence and stability of the steady states are considered. We address an analytical expression for the reproductive number in a community where antiretroviral therapy are widely used to treat HIV and where both drug sensitive and drug resistant strains are co-circulating.

  10. Effects of combination antiretroviral therapies on the risk for myocardial infarction among HIV patients

    PubMed Central

    Brouwer, Emily S.; Napravnik, Sonia; Eron, Joseph J; Stalzer, Brant; Floris-Moore, Michelle; Simpson, Ross J; Stürmer, Til

    2014-01-01

    Background Cohort studies have demonstrated greater risk of myocardial infarction (MI) associated with specific antiretroviral use, while meta-analyses of randomized controlled trials have not. These differences may be due to inherent biases in the observational study design or to the limited duration of randomized trials. We conducted a new-user, active-comparator cohort study emulating a randomized controlled trial comparing initiation of several antiretrovirals as part of combination antiretroviral therapy (cART) and MI. Methods We included North Carolina (NC) Medicaid beneficiaries infected with HIV between 2002 and 2008 who were previously untreated with cART. We compared hazard ratios (HRs) and 95% confidence intervals (CIs) of MI between abacavir and tenofovir recipients, and lopinavir-ritonavir or atazanavir recipients and non-nucleoside-reverse-transcriptase-inhibitor (NNRTI) recipients. We adjusted for confounding through inverse-probability-weighting methods. Results There were 3,481 NC Medicaid new cART recipients who contributed 6,399 person-years and experienced 38 MI events. Receiving abacavir compared with tenofovir as part of cART was associated with an increased rate of MI unadjusted (HR= 2.70 [95% CI= 1.24 - 5.91]; HR= 2.05 [0.72 - 5.86]). Point estimates also suggest a relationship between receipt of atazanavir or lopinavir-ritonavir compared with an NNRTI and MI, although, estimates were imprecise. Conclusions We found an increased rate of MI among patients initiating abacavir compared with tenofovir although the association was decreased after confounding adjustment. Without a very large prospective comparative clinical trial, a much larger observational study of patients initiating cART would be needed to better define this apparent association. PMID:24713880

  11. [Antiretroviral therapy in human immunodeficiency virus infection: an update].

    PubMed

    Chaix, F; Goujard, C

    2009-06-01

    Since the onset of the human immunodeficiency virus (HIV) epidemic, the care of infected patients improved dramatically. Whereas the disease was almost always fatal, the development of new drugs and new therapeutic strategies now allow a prolonged survival. However, the complexity of patient care is increasing and physicians face new clinical events and treatment toxicities. Recent molecules and follow-up according to the recent French recommendations will be presented here. The objectives of the treatment is to decrease mortality and morbidity of the HIV infection, by restoring near normal CD4+ T cell counts and qualitative T CD4+ responses, associated with a sustained reduction in viral replication. This objective must be reached by minimizing toxicity of antiretroviral drugs. Newly developed drugs that are better-tolerated and new therapeutic classes should improve outcome at all stages of HIV infection. Whereas viral eradication remains unrealistic and protective vaccines will not be soon available, direct consequences of long term HIV infection and issues related to an ageing HIV infected population raise up new research topics. Prevention of new infections, improvement in the precocity of care by a better-targeted screening and assessment of therapy before an established immune deficiency appear as the main priorities for the coming years. PMID:19237230

  12. Development of HIV reservoir targeted long acting nanoformulated antiretroviral therapies.

    PubMed

    Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

    2014-01-01

    Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection.

  13. Development of HIV Reservoir Targeted Long Acting Nanoformulated Antiretroviral Therapies

    PubMed Central

    Edagwa, Benson J; Zhou, Tian; McMillan, JoEllyn M; Liu, Xin-Ming; Gendelman, Howard E

    2014-01-01

    Human immunodeficiency virus (HIV) infection commonly results in a myriad of comorbid conditions secondary to immune deficiency. Infection also affects broad organ system function. Although current antiretroviral therapy (ART) reduces disease morbidity and mortality through effective control of peripheral viral load, restricted infection in HIV reservoirs including gut, lymphoid and central nervous system tissues, is not eliminated. What underlies these events is, in part, poor ART penetrance into each organ across tissue barriers, viral mutation and the longevity of infected cells. We posit that one means to improve these disease outcomes is through nanotechnology. To this end, this review discusses a broad range of cutting-edge nanomedicines and nanomedicine platforms that are or can be used to improve ART delivery. Discussion points include how polymer-drug conjugates, dendrimers, micelles, liposomes, solid lipid nanoparticles and polymeric nanoparticles can be harnessed to best yield cell-based delivery systems. When completely developed, such nanomedicine platforms have the potential to clear reservoirs of viral infection. PMID:25174930

  14. Namibian prisoners describe barriers to HIV antiretroviral therapy adherence.

    PubMed

    Shalihu, Nauyele; Pretorius, Louise; van Dyk, Agnes; Vander Stoep, Ann; Hagopian, Amy

    2014-01-01

    Little is available in scholarly literature about how HIV-positive prisoners, especially in low-income countries, access antiretroviral therapy (ART) medication. We interviewed 18 prisoners at a large prison in Namibia to identify barriers to medication adherence. The lead nurse researcher was a long-standing clinic employee at the prison, which afforded her access to the population. We identified six significant barriers to adherence, including (1) the desire for privacy and anonymity in a setting where HIV is strongly stigmatized; (2) the lack of simple supports for adherence, such as availability of clocks; (3) insufficient access to food to support the toll on the body of ingesting taxing ART medications; (4) commodification of ART medication; (5) the brutality and despair in the prison setting, generally leading to discouragement and a lack of motivation to strive for optimum health; and (6) the lack of understanding about HIV, how it is transmitted, and how it is best managed. Because most prisoners eventually transition back to communitysettings when their sentences are served, investments in prison health represent important investments in public health. PMID:24499371

  15. Common mental health problems and antiretroviral therapy adherence.

    PubMed

    Nel, Adriaan; Kagee, Ashraf

    2011-11-01

    This paper reviews the literature on various mental health problems and their impact on adherence to antiretroviral therapy (ART). Depression, anxiety disorders, and disorders related to substance abuse were identified as key role-players influencing adherence. The severity of symptoms related to these disorders was found to be inversely related to ART adherence, with the possible exception of post-traumatic stress disorder (PTSD). PTSD was found to have both positive and negative implications for adherence, with severity of symptoms ranging from health-protective concern to disabling distress. Possible solutions aimed at addressing the adverse effects of mental health problems on adherence are discussed. Routine screening in ART settings is suggested in settings where follow-up of positive screen scores are possible, along with the necessary interventions to resolve the disorder of concern. Suggested interventions include utilising psychotherapeutic treatment, both in isolation and in conjunction with medication, to address mental health problems. Furthermore, finding effective ways of marshalling social support is recommended for ensuring optimal adherence, and possibly mitigating the adverse effects of mental health problems. Further research is needed to find feasible ways of identifying, assessing and treating patients with mental health problems in resource-constrained settings where HIV prevalence is highest.

  16. Antiretroviral Therapy and Central Nervous System HIV-1 Infection

    PubMed Central

    Price, Richard W.; Spudich, Serena

    2008-01-01

    Central nervous system (CNS) HIV-1 infection begins during primary viremia and continues throughout the course of untreated systemic infection. While frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection is not usually clinically apparent. In a minority of patients, CNS HIV-1 infection evolves late in the course of systemic infection into encephalitis, which compromises brain function and presents clinically as AIDS dementia complex (ADC). Combination highly active antiretroviral therapy (HAART) has had a major impact on all aspects of HIV-1 CNS infection and disease. In those with asymptomatic infection, HAART usually effectively suppresses CSF HIV-1 and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, HAART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Treatment has similarly reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection, and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention. PMID:18447615

  17. Reactive arthritis responding to antiretroviral therapy in an HIV-1-infected individual.

    PubMed

    Scott, C; Brand, A; Natha, M

    2012-05-01

    Reactive arthritis (ReA) is an autoimmune seronegative spondyloarthropathy that occurs in response to a urogenital or enteric infection. Several studies have reported a link between ReA and HIV infection. We report a case of an HIV-1-infected patient diagnosed with a disabling ReA who failed to respond to conventional therapy but whose symptoms resolved rapidly after starting antiretroviral therapy (ART). Clinicians may not be cognizant to this phenomenon and so this case report serves to remind clinicians that initiation of antiretroviral therapy should be considered in HIV-infected patients with ReA who are refractory to standard therapy.

  18. Virological Response and Antiretroviral Drug Resistance Emerging during Antiretroviral Therapy at Three Treatment Centers in Uganda

    PubMed Central

    Kaleebu, Pontiano; Kirungi, Wilford; Watera, Christine; Asio, Juliet; Lyagoba, Fred; Lutalo, Tom; Kapaata, Anne A.; Nanyonga, Faith; Parry, Chris M.; Magambo, Brian; Nazziwa, Jamirah; Nannyonjo, Maria; Hughes, Peter; Hladik, Wolfgang; Ruberantwari, Anthony; Namuwenge, Norah; Musinguzi, Joshua; Downing, Robert; Katongole-Mbidde, Edward

    2015-01-01

    Background With the scale-up of antiretroviral therapy (ART), monitoring programme performance is needed to maximize ART efficacy and limit HIV drug resistance (HIVDR). Methods We implemented a WHO HIVDR prospective survey protocol at three treatment centers between 2012 and 2013. Data were abstracted from patient records at ART start (T1) and after 12 months (T2). Genotyping was performed in the HIV pol region at the two time points. Results Of the 425 patients enrolled, at T2, 20 (4.7%) had died, 66 (15.5%) were lost to follow-up, 313 (73.6%) were still on first-line, 8 (1.9%) had switched to second-line, 17 (4.0%) had transferred out and 1 (0.2%) had stopped treatment. At T2, 272 out of 321 on first and second line (84.7%) suppressed below 1000 copies/ml and the HIV DR prevention rate was 70.1%, just within the WHO threshold of ≥70%. The proportion of participants with potential HIVDR was 20.9%, which is higher than the 18.8% based on pooled analyses from African studies. Of the 35 patients with mutations at T2, 80% had M184V/I, 65.7% Y181C, and 48.6% (54.8% excluding those not on Tenofovir) had K65R mutations. 22.9% had Thymidine Analogue Mutations (TAMs). Factors significantly associated with HIVDR prevention at T2 were: baseline viral load (VL) <100,000 copies/ml [Adjusted odds ratio (AOR) 3.13, 95% confidence interval (CI): 1.36–7.19] and facility. Independent baseline predictors for HIVDR mutations at T2 were: CD4 count <250 cells/μl (AOR 2.80, 95% CI: 1.08–7.29) and viral load ≥100,000 copies/ml (AOR 2.48, 95% CI: 1.00–6.14). Conclusion Strengthening defaulter tracing, intensified follow-up for patients with low CD4 counts and/or high VL at ART initiation together with early treatment initiation above 250 CD4 cells/ul and adequate patient counselling would improve ART efficacy and HIVDR prevention. The high rate of K65R and TAMs could compromise second line regimens including NRTIs. PMID:26700639

  19. Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

    PubMed Central

    Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

    2006-01-01

    OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

  20. Antiretroviral Therapy for the Prevention of HIV-1 Transmission.

    PubMed

    Cohen, Myron S; Chen, Ying Q; McCauley, Marybeth; Gamble, Theresa; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kumwenda, Johnstone; Grinsztejn, Beatriz; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; Santos, Breno R; Mayer, Kenneth H; Hoffman, Irving F; Eshleman, Susan H; Piwowar-Manning, Estelle; Cottle, Leslie; Zhang, Xinyi C; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Faesen, Sharlaa; Eron, Joseph; Gallant, Joel; Havlir, Diane; Swindells, Susan; Elharrar, Vanessa; Burns, David; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David D; Essex, Max; Hudelson, Sarah E; Redd, Andrew D; Fleming, Thomas R

    2016-09-01

    Background An interim analysis of data from the HIV Prevention Trials Network (HPTN) 052 trial showed that antiretroviral therapy (ART) prevented more than 96% of genetically linked infections caused by human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. ART was then offered to all patients with HIV-1 infection (index participants). The study included more than 5 years of follow-up to assess the durability of such therapy for the prevention of HIV-1 transmission. Methods We randomly assigned 1763 index participants to receive either early or delayed ART. In the early-ART group, 886 participants started therapy at enrollment (CD4+ count, 350 to 550 cells per cubic millimeter). In the delayed-ART group, 877 participants started therapy after two consecutive CD4+ counts fell below 250 cells per cubic millimeter or if an illness indicative of the acquired immunodeficiency syndrome (i.e., an AIDS-defining illness) developed. The primary study end point was the diagnosis of genetically linked HIV-1 infection in the previously HIV-1-negative partner in an intention-to-treat analysis. Results Index participants were followed for 10,031 person-years; partners were followed for 8509 person-years. Among partners, 78 HIV-1 infections were observed during the trial (annual incidence, 0.9%; 95% confidence interval [CI], 0.7 to 1.1). Viral-linkage status was determined for 72 (92%) of the partner infections. Of these infections, 46 were linked (3 in the early-ART group and 43 in the delayed-ART group; incidence, 0.5%; 95% CI, 0.4 to 0.7) and 26 were unlinked (14 in the early-ART group and 12 in the delayed-ART group; incidence, 0.3%; 95% CI, 0.2 to 0.4). Early ART was associated with a 93% lower risk of linked partner infection than was delayed ART (hazard ratio, 0.07; 95% CI, 0.02 to 0.22). No linked infections were observed when HIV-1 infection was stably suppressed by ART in the index participant. Conclusions The early initiation of ART led to a sustained

  1. Association between HIV in pregnancy and antiretroviral therapy, including protease inhibitors and low birth weight infants.

    PubMed Central

    Goldstein, P J; Smit, R; Stevens, M; Sever, J L

    2000-01-01

    OBJECTIVE: To determine the incidence of low birth weight infants born to HIV seropositive women and to demonstrate any effects of antiretroviral therapy on birth weight. METHODS: Retrospective review of all obstetrical medical records from January 1, 1995 through June 30, 1998 to identify HIV seropositive women. We evaluated their antiretroviral therapy, CD4 counts, and birth weights of their newborns. We conducted detailed review of the clinical and laboratory findings for the HIV-infected untreated patients, women who received ZDV antepartum alone, and those who received PIs as part of antiretroviral treatment. RESULTS: The frequency of low birth weight infants was significantly increased in HIV seropositive compared to HIV seronegative parturients. Low birth weight infants were more frequent among HIV infected women with lower CD4 counts but the association was not statistically significant. Women who received no antepartum treatment, antepartum only ZDV, and those treated with PIs had significantly more low birth weight infants than did comparison groups. HIV seropositive women also had high frequencies of several obstetrical risk factors for low birth weight infants. CONCLUSION: The present study showed a significantly increased frequency of low birth weight infants among HIV infected women and especially the subgroups of infected women who received no antepartum treatment, antepartum ZDV only, and those treated with PIs. This association, however, may be related to the presence of many other preterm obstetrical risk factors noted in this study. Increasing numbers of HIV seropositive women are being treated with PIs according to the Centers for Disease Control (CDC) guidelines. If PIs are a cause of low birth weight infants, women taking these drugs may have incremental risk of low birth weight. PMID:10805364

  2. Transcriptional Changes in CD8+ T Cells During Antiretroviral Therapy Intensified With Raltegravir

    PubMed Central

    Ouyang, Zhengyu; Buzon, Maria J.; Zheng, Lu; Sun, Hong; Yu, Xu G.; Bosch, Ronald J.; Mellors, John W.; Eron, Joseph J.; Gandhi, Rajesh T.; Lichterfeld, Mathias

    2015-01-01

    Background. Intensification of antiretroviral therapy with raltegravir does not affect levels of residual human immunodeficiency virus (HIV)-1 viremia, but it has led to increased levels of episomal HIV-1 DNA in some patients, suggesting antiviral activity against otherwise unresponsive components of the viral reservoir. Effects of raltegravir on host cells remain less well understood. Methods. We used comprehensive and unbiased microarray-based transcriptional profiling to analyze gene expression changes in CD8+ T cells from participants in a randomized clinical trial (AIDS Clinical Trials Group [ACTG] A5244) comparing raltegravir-intensified to nonintensified antiretroviral therapy. Results. Although raltegravir intensification failed to induce statistically significant changes in HIV-1 DNA or residual plasma viremia, we observed significant increases in the expression intensity of 121 host gene transcripts. In functional annotations of these transcripts, we found that they were mainly involved in glucose and carbohydrate metabolism, immune regulation, control of cell proliferation, and tumor suppression. Two of the raltegravir-responsive gene transcripts were statistically correlated with levels of residual HIV-1 RNA, but none of the remaining 119 transcripts were associated with immunologic or virologic characteristics of the study patients. Conclusions. Together, these findings demonstrate that raltegravir intensification can induce previously unrecognized, statistically significant gene expression changes in host CD8+ T lymphocytes. PMID:26380343

  3. Cellular Responses and Tissue Depots for Nanoformulated Antiretroviral Therapy

    PubMed Central

    Martinez-Skinner, Andrea L.; Araínga, Mariluz A.; Puligujja, Pavan; Palandri, Diana L.; Baldridge, Hannah M.; Edagwa, Benson J.; McMillan, JoEllyn M.; Mosley, R. Lee; Gendelman, Howard E.

    2015-01-01

    Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, CD3, CD11b, F4/80, and GR-1 antibodies. The localization of nanoATV within leukocyte cell subsets was determined by confocal microscopy. Combined FACS and ultra-performance liquid chromatography tandem mass-spectrometry assays determined nanoATV carriages by cell-based vehicles. A robust granulocyte, but not peritoneal macrophage nanoATV response paralleled zymosan A treatment. ATV levels were highest at sites of injection in peritoneal or muscle macrophages, dependent on the injection site. The spleen and liver served as nanoATV tissue depots while drug levels in lymph nodes were higher than those recorded in plasma. Dual polymer and cell labeling demonstrated a nearly exclusive drug reservoir in macrophages within the liver and spleen. Overall, nanoART induces innate immune responses coincident with rapid tissue macrophage distribution. Taken together, these works provide avenues for therapeutic development designed towards chemical eradication of human immunodeficiency viral infection. PMID:26716700

  4. The Survival Benefits of Antiretroviral Therapy in South Africa

    PubMed Central

    April, Michael D.; Wood, Robin; Berkowitz, Bethany K.; Paltiel, A. David; Anglaret, Xavier; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2014-01-01

    Background. We sought to quantify the survival benefits attributable to antiretroviral therapy (ART) in South Africa since 2004. Methods. We used the Cost-Effectiveness of Preventing AIDS Complications–International model (CEPAC) to simulate 8 cohorts of human immunodeficiency virus (HIV)–infected patients initiating ART each year during 2004–2011. Model inputs included cohort-specific mean CD4+ T-cell count at ART initiation (112–178 cells/µL), 24-week ART suppressive efficacy (78%), second-line ART availability (2.4% of ART recipients), and cohort-specific 36-month retention rate (55%–71%). CEPAC simulated survival twice for each cohort, once with and once without ART. The sum of the products of per capita survival differences and the total numbers of persons initiating ART for each cohort yielded the total survival benefits. Results. Lifetime per capita survival benefits ranged from 9.3 to 10.2 life-years across the 8 cohorts. Total estimated population lifetime survival benefit for all persons starting ART during 2004–2011 was 21.7 million life-years, of which 2.8 million life-years (12.7%) had been realized by December 2012. By 2030, benefits reached 17.9 million life-years under current policies, 21.7 million life-years with universal second-line ART, 23.3 million life-years with increased linkage to care of eligible untreated patients, and 28.0 million life-years with both linkage to care and universal second-line ART. Conclusions. We found dramatic past and potential future survival benefits attributable to ART, justifying international support of ART rollout in South Africa. PMID:24307741

  5. Alcohol use disorders and antiretroviral therapy among prisoners in Argentina

    PubMed Central

    Alpert, Michael; Wickersham, Jeffrey A.; Vázquez, Mariana; Altice, Frederick L.

    2013-01-01

    Purpose While Argentina has significantly improved access to HIV care and antiretroviral therapy (ART) for both the general population and prisoners, the prevalence of alcohol use disorders (AUDs) among HIV-infected prisoners and their relationship to accessing ART in Argentina is currently unknown. This study aims to characterize the substance abuse patterns of HIV-infected prisoners in Argentina and to assess the independent correlates of receipt of pre-incarceration ART. Design/methodology/approach An anonymous, cross-sectional survey of 100 HIV-infected federal prisoners was conducted in the Buenos Aires municipality from July–December 2010. AUDs were assessed using the AUDIT scale. Findings A majority (63 per cent) of participants met criteria for AUDs, 45 per cent of subjects were diagnosed with HIV in prison and one-quarter had initiated ART during the current incarceration. In addition, over one-third (35 per cent) of participants did not receive ART during the pre-incarceration period despite receiving it upon incarceration. This correlated significantly with the presence of having an AUD (AOR 0.20, 95 per cent CI 0.06–0.74, p = 0.016). Practical implications AUDs are prevalent among HIV-infected prisoners in Argentina and are significantly related to negative secondary HIV prevention and treatment outcomes. While Argentina has provided an exemplary model of HIV-related health care reform within its prisons, future efforts to provide screening and treatment for AUDs are needed to improve the health of the nation’s incarcerated population. Originality/value This paper is the first to describe pre-incarceration drug and alcohol use disorders and issues related to access to ART among prisoners in Argentina. PMID:24772187

  6. A pilot study of health beliefs and attitudes concerning measures of antiretroviral adherence among prisoners receiving directly observed antiretroviral therapy.

    PubMed

    White, Becky L; Wohl, David A; Hays, Ron D; Golin, Carol E; Liu, Honghu; Kiziah, C Nichole; Simpson, Gregory; Kaplan, Andrew H

    2006-06-01

    High level adherence to antiretroviral therapy (ART) is required to achieve and maintain suppression of HIV replication. Although directly observed therapy (DOT) has been suggested as an intervention to improve adherence, there is a paucity of data describing the attitudes and beliefs regarding DOT for ART among HIV-infected individuals. This study was designed to evaluate the acceptability and psychometric properties of a survey instrument for use in assessing barriers and facilitators of adherence to ART DOT in prison. From July 1, 1999 to April 1, 2000, we piloted an interviewer-administered questionnaire to assess health beliefs and attitudes regarding HIV treatment among 65 HIV-infected prison inmates receiving one or more of their antiretrovirals via directly observed therapy (DOT). The first 24 participants were administered the questionnaire to determine the feasibility of surveying prisoners in a correctional setting. There were no adherence data collected on these participants. The remaining 41 participants had their adherence measured in addition to receiving the questionnaire. Thirty-one were included in the final analysis because 10 did not complete the study. Multiple antiretroviral adherence measures (electronic device medication monitoring [eDEM] caps, medication administration records [MARs], and pill counts) were assessed among a subset of the participants (n = 31) and correlated to the instrument response items. The median internal consistency reliability coefficient for the multi-item scales was 0.79. The strongest correlation between inmates' beliefs and their adherence was between "positive beliefs about protease inhibitors" and the MAR adherence measure (r = 0.72; p < 0.001). This study provides preliminary support for the psychometric properties of the survey in this correctional setting. PMID:16789854

  7. Antiretroviral Therapy as HIV Prevention: Status and Prospects

    PubMed Central

    Venkatesh, Kartik K.

    2010-01-01

    As antiretroviral treatment of HIV infection has become increasingly accessible, attention has focused on whether these drugs can used for prevention because of increased tolerability of newer medications, decreased cost, and the limitations of other approaches. We review the status of antiretroviral HIV prevention, including chemoprophylaxis, as well as the effects of treatment of infected individuals on prevention. It is possible that the life-saving agents that have transformed the natural history of AIDS can be a critical component of HIV prevention efforts, but their ultimate role in affecting HIV transmission dynamics remains to be defined. PMID:20724682

  8. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    PubMed

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/μL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients. PMID:24756590

  9. Ophthalmic manifestations of HIV in the highly active anti-retroviral therapy era.

    PubMed

    Mowatt, L

    2013-01-01

    HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/μL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/μL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/μL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients.

  10. Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

    PubMed Central

    Tavel, Jorge A.

    2010-01-01

    Background The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4+ counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009). Conclusions IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells. Trial Registration ClinicalTrials.gov NCT00110812 PMID:20186278

  11. Magnetic resonance imaging evaluation of lipodystrophy in HIV-positive patients receiving highly active antiretroviral therapy.

    PubMed

    Eichler, K; Bickel, T M; Klauke, S; Eisen, J; Vogl, T J; Zangos, S

    2015-07-01

    We evaluated retrospectively an automated method for the separate detection of subcutaneous and visceral fat in the abdominal region by magnetic resonance studies in HIV-positive patients on highly active antiretroviral therapy. The patients were divided into four different groups: lipoatrophy, lipohypertrophy, mixed and the control group. The use of software for the automated detection of abdominal compartment visceral adipose tissue (VAT), total adipose tissue (TAT) and subcutaneous adipose tissue (SAT) was compared to manual evaluation methods (fuzzy C-mean). The results of ROC analysis showed that the parameters, particularly the VAT, are better than the VAT/TAT and at identifying patients with the symptoms of abdominal fat accumulation. A sensitivity of 80.3% and a specificity of 79.5% resulted from a threshold VAT value of >87 cm(2). Moreover, the manual evaluation method was shown to provide greater values for VAT and the VAT/TAT ratio than those given by the automated method. In the present study, a rapid MRI protocol for the detection and assessment of the course of lipodystrophy was presented and tested on a group of patients with signs of HALS, as well as on an antiretroviral naïve control group.

  12. [Ergotism due to simultaneous use of ergot alkaloids and high activity antiretroviral therapy].

    PubMed

    Cifuentes M, Daniel; Blanco L, Sergio; Ramírez F, Camila

    2016-06-01

    High activity antiretroviral therapy may exacerbate the activity of ergot alkaloids due to an inhibition of cytochrome P450. We report a 57 years old female with AIDS treated with lamivudine, zidovudine, atazanavir, ritonavir and cotrimoxazole presenting with ischemic signs in the four limbs. There was acrocyanosis and weak radial and ulnar pulses. A family member referred that the patient used ergot alkaloids for headaches. An ergotism due to the simultaneous use of ergot alkaloids and antiretroviral therapy was suspected. The latter was discontinued and intravenous nitroglycerin, nifedipine and pentoxifyline were started with good results. PMID:27598502

  13. Is early antiretroviral therapy initiation useful in HIV(+) adults without co-infections?

    PubMed

    Chauriye, Verónica; Monsalve, Ximena

    2015-12-02

    HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects.

  14. Is early antiretroviral therapy initiation useful in HIV(+) adults without co-infections?

    PubMed

    Chauriye, Verónica; Monsalve, Ximena

    2015-01-01

    HIV infection is a worldwide epidemic. Antiretroviral therapy has dramatically changed the outcome of the disease but there is still controversy about the best time to initiate it, especially in patients with CD4 counts over 350 cells/µL. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including four pertinent randomized controlled trials overall. We concluded early initiation of antiretroviral therapy probably reduces mortality, risk of opportunistic infections and tuberculosis, but increases the risk of important adverse effects. PMID:26639366

  15. Can antiretroviral therapy be used to prevent sexual transmission of human immunodeficiency virus type 1?

    PubMed

    Hosseinipour, Mina; Cohen, Myron S; Vernazza, Pietro L; Kashuba, Angela D M

    2002-05-15

    Approximately 5 million people annually are newly infected with human immunodeficiency virus (HIV). Although education, behavior modification, and promotion of condom use are effective transmission-prevention measures, the severity of the pandemic demands that all possible prevention strategies be explored. Antiretroviral therapy has the potential to decrease sexual transmission of HIV type 1 by reducing levels of HIV RNA and thus decreasing the risk that infected persons will transmit the disease or by its use as preexposure or postexposure prophylaxis. In this article, we explore the rationale for using antiretroviral therapy to prevent sexual transmission of HIV, as well as the limitations of this approach. PMID:11981736

  16. Depo-medroxyprogesterone in women on antiretroviral therapy: effective contraception and lack of clinically significant interactions.

    PubMed

    Cohn, S E; Park, J-G; Watts, D H; Stek, A; Hitti, J; Clax, P A; Yu, S; Lertora, J J L

    2007-02-01

    We conducted an open-label, steady-state pharmacokinetic (PK) study of drug interactions among HIV-infected women treated with depo-medroxyprogesterone acetate (DMPA) while on nucleoside analogues plus nelfinavir (N=21), efavirenz (N=17), or nevirapine (N=16); or nucleosides only or no antiretroviral therapy as a control group (N=16). PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PKs and within-subject comparisons of ARV PKs before and 4 weeks after DMPA dosing. Plasma progesterone levels were measured at baseline and at 2, 4, 6, 8, 10, and 12 weeks after DMPA dosing. There were no significant changes in MPA area under the concentration curve, peak or trough concentrations, or apparent clearance in the nelfinavir, efavirenz, or nevirapine groups compared to the control group. Minor changes in nelfinavir and nevirapine drug exposure were seen after DMPA, but were not considered clinically significant. Suppression of ovulation was maintained.

  17. Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta-Analysis

    PubMed Central

    Low, Andrea J.; Mburu, Gitau; Welton, Nicky J.; May, Margaret T.; Davies, Charlotte F.; French, Clare; Turner, Katy M.; Looker, Katharine J.; Christensen, Hannah; McLean, Susie; Rhodes, Tim; Platt, Lucy; Hickman, Matthew; Guise, Andy; Vickerman, Peter

    2016-01-01

    Background. Human immunodeficiency virus (HIV)–infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. Methods. We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I2 statistic. Results. We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32–2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17–2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41–3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63–.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21–1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65–1.25). Conclusions. These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID. PMID:27343545

  18. Regression of both oral mucocele and parotid swellings, following antiretroviral therapy.

    PubMed

    Syebele, Kabunda

    2010-01-01

    HIV-salivary gland associated disease is a well accepted concept in the HIV-related literature. Parotid swellings, especially in its cystic benign lymphoepithelial form, have been largely reported. Oral mucoceles (ranulas) were also associated with HIV in some publications. The exact nature of this link between mucoceles and HIV is still to be clarified. The mainstream treatment of most of parotid pathologies and oral mucoceles remains surgical approach. Strong evidences do, however, exist about lymphopithelial lesions of parotid glands that have been successfully treated with antiretroviral drugs. We present a case of intraoral mucocele, coexisting with bilateral parotid gland lymphoepithelial lesions, on a 2-year-old HIV-positive patient. Both parotid gland swellings and the sublingual mucocele have completely regressed following antiretroviral therapy. No surgical intervention was required. Conversely to benign lymphoepithelial lesions of parotid glands, the regression of oral mucocele on HIV-positive patient, following antiretroviral drugs therapy appears to be a rare phenomenon.

  19. [SSRI AND BONE METABOLISM IN HIV + PATIENTS WITH ANTIRETROVIRAL THERAPY].

    PubMed

    Mazzoglio y Nabar, Martín J; Muñiz, Milagros María; Mejías Delamano, Alexis A; Muñoz, Santiago; Magrath Guimet, Nahuel

    2015-01-01

    We report a series of 9 male HIV + patients, average age of 41.2 years, viral load negative (<50 copies RNA/ml), treated with antiretroviral (nucleoside and non-nucleoside inhibitors of reverse transcriptase) without systemic infections, the CNS diseases or marker or corticoidoterapia in progress. Were evaluated and supported by their infectologists interconsultation during the period October 2008-October 2013 by depressive syndrome. Psychotherapeutic and psychiatric treatment was initiated with SSRIs and clonazepam; Neuroimaging control and biochemical laboratory studies at baseline and 2 months of treatment were conducted. In the course of psychopharmacological treatment not suffer fractures due to falls and alterations were detected in bone metabolism markers and images. He studied with endocrinology and interdisciplinary medical clinic, decided to withdraw the SSRIs with normalization of biochemical values and psychotherapeutic treatment was continued. We will raise the associations between the use of SSRIs, disturbances of bone metabolism with clinical correlation and possible drug interactions between antidepressants and antiretroviral. PMID:26650557

  20. 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

  1. Modulation of HCV Replication After Combination Antiretroviral Therapy in HCV/HIV Coinfected Patients

    PubMed Central

    Sherman, Kenneth E.; Guedj, Jeremie; Shata, Mohamed Tarek; Blackard, Jason T.; Rouster, Susan D.; Castro, Mario; Feinberg, Judith; Sterling, Richard K.; Goodman, Zachary; Aronow, Bruce J.; Perelson, Alan S.

    2015-01-01

    The hepatitis C virus (HCV) is an important contributor to morbidity and mortality in patients coinfected with human immunodeficiency virus (HIV). Coinfection results in increased HCV replication and more rapid rates of liver disease progression. The effect of HIV combination antiretroviral therapy (cART) on HCV replication has not been studied in depth. To address this issue, we enrolled a small cohort of HCV/HIV coinfected patients into a cART initiation trial, and used dynamic modeling combined with evaluation of immune responses and microarray profiles to determine how effective treatment of HIV affects HCV. Treatment with cART resulted in HCV flare and alanine aminotransferase (ALT) increase (2× or more increase from baseline) in a subset of treated patients. Subjects with evidence of hepatic injury (increased ALT) were more likely to have HCV-specific immune responses directed against HCV epitopes. Over time, HCV viral loads declined. Reproducible and biologically important gene expression changes occurred in patients who underwent successful cART, particularly with respect to downregulation of genes with known antiviral roles. Our findings suggest that the effective suppression of HIV by cART initiates a cascade of early and late events in treated patients with HCV. Early events involving downregulation of interferon-stimulated genes may lead to transiently increased viral replication and hepatic injury. At later time points, HCV viral load declines to levels comparable to those seen in the setting of HCV monoinfection. These findings support early antiretroviral therapy in those with HCV/HIV coinfection. PMID:25101888

  2. Highly Active Antiretroviral Therapy and Adverse Birth Outcomes Among HIV-Infected Women in Botswana

    PubMed Central

    Chen, Jennifer Y.; Ribaudo, Heather J.; Souda, Sajini; Parekh, Natasha; Ogwu, Anthony; Lockman, Shahin; Powis, Kathleen; Dryden-Peterson, Scott; Creek, Tracy; Jimbo, William; Madidimalo, Tebogo; Makhema, Joseph; Essex, Max; Shapiro, Roger L

    2012-01-01

    Background. It is unknown whether adverse birth outcomes are associated with maternal highly active antiretroviral therapy (HAART) in pregnancy, particularly in resource-limited settings. Methods. We abstracted obstetrical records at 6 sites in Botswana for 24 months. Outcomes included stillbirths (SBs), preterm delivery (PTD), small for gestational age (SGA), and neonatal death (NND). Among human immunodeficiency virus (HIV)–infected women, comparisons were limited to HAART exposure status at conception, and those with similar opportunities for outcomes. Comparisons were adjusted for CD4+ lymphocyte cell count. Results. Of 33 148 women, 32 113 (97%) were tested for HIV, of whom 9504 (30%) were HIV infected. Maternal HIV was significantly associated with SB, PTD, SGA, and NND. Compared with all other HIV-infected women, those continuing HAART from before pregnancy had higher odds of PTD (adjusted odds ratio [AOR], 1.2; 95% confidence interval [CI], 1.1, 1.4), SGA (AOR, 1.8; 95% CI, 1.6, 2.1) and SB (AOR, 1.5; 95% CI, 1.2, 1.8). Among women initiating antiretroviral therapy in pregnancy, HAART use (vs zidovudine) was associated with higher odds of PTD (AOR, 1.4; 95% CI, 1.2, 1.8), SGA (AOR, 1.5; 95% CI, 1.2, 1.9), and SB (AOR, 2.5; 95% CI, 1.6, 3.9). Low CD4+ was independently associated with SB and SGA, and maternal hypertension during pregnancy with PTD, SGA, and SB. Conclusions. HAART receipt during pregnancy was associated with increased PTD, SGA, and SB. PMID:23066160

  3. The consequences of post-election violence on antiretroviral HIV therapy in Kenya

    PubMed Central

    Pyne-Mercier, Lee D.; John-Stewart, Grace C.; Richardson, Barbra A.; Kagondu, Njeri L.; Thiga, Joan; Noshy, Haidy; Kist, Nadia; Chung, Michael H.

    2012-01-01

    Over 1000 individuals were killed and 600,000 were displaced during post-election violence (PEV) in Kenya in 2008. Antiretroviral therapy (ART) depends on continuous access to medications which may have been interrupted due to PEV. In a mixed-methods retrospective review, treatment interruption of ART during PEV was measured among 2534 HIV-positive adults attending the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya. Clients experiencing treatment interruption were compared between the PEV period (30 December 2007 to 28 February 2008) and the same time period one year earlier. Treatment interruption was defined as visiting the pharmacy ≥48 hours after antiretrovirals were calculated to have been completed. Despite clinical services remaining open throughout the PEV period, more clients (16.1%) experienced treatment interruption than during the comparison period (10.2%). Mean daily pharmacy visits were significantly lower (87 vs. 104; p < 0.006) and more variable (p = 0.03) during PEV. Among clients present at both periods (n = 1605), the odds of treatment interruption were 71% higher during PEV (95% confidence interval [CI], 34–118%). In multivariate analysis, men (odds ratio [OR], 1.37; 95% CI, 1.07–1.76) and clients traveling ≥3 hours to clinic (OR, 1.86; 95% CI, 1.28–2.71) were significantly more likely to experience treatment interruption. Clients affected by PEV were interviewed about factors associated with treatment interruption using semi-structured methods. Clients described fear, lack of transportation, and violence as contributing to treatment interruption. Widespread violence associated with the 2007 election in Kenya revealed the dependence of HIV patients on a stable civil society and infrastructure to access medications. Without the ability to maintain consistent HIV therapy, some patients face rapid treatment failure. HIV programs should have appropriate contingency plans wherever political instability may occur. Peace may be

  4. Antiretroviral therapy, labor productivity, and gender: a longitudinal cohort study of tea pluckers in Kenya

    PubMed Central

    LARSON, Bruce. A.; FOX, Matthew P.; BII, Margaret; ROSEN, Sydney; ROHR, Julia; SHAFFER, Douglas; SAWE, Fredrick; WASUNNA, Monique; SIMON, Jonathon L.

    2014-01-01

    Objective To estimate the impact of antiretroviral therapy (ART) on labor productivity and income using detailed employment data from two large tea plantations in western Kenya for HIV-infected tea pluckers who initiated ART. Design Longitudinal study using primary data on key employment outcomes for a group of HIV-infected workers receiving anti-retroviral therapy (ART) and workers in the general workforce. Methods We used nearest-neighbor matching methods to estimate the impacts of HIV/AIDS and ART among 237 HIV-positive pluckers on ART (index group) over a four year period (2 years pre- and post-ART) on four monthly employment outcomes—days plucking tea, total kilograms harvested, total days working, and total labor income. Outcomes for the index group were compared to those for a matched reference group from the general workforce. Results We observed a rapid deterioration in all four outcomes for HIV-infected subjects in the period before ART initiation and then a rapid improvement after treatment initiation. By 18–24 months after treatment initiation, the index group harvested 8% (males) and 19% (females) less tea than reference subjects. The index group earned 6% (males) and 9% (females) less income from labor than reference subjects. Women’s income would have dropped further if they had not been able to offset their decline in tea plucking by spending more time on non-plucking assignments. Conclusions HIV-infected workers experienced long-term income reductions before and after initiating ART. The implications of such long-term impacts in low-income countries have not been adequately addressed. PMID:23014516

  5. Hepatic steatosis in HIV-HCV coinfected patients receiving antiretroviral therapy is associated with HCV-related factors but not antiretrovirals

    PubMed Central

    2012-01-01

    Background In HIV and hepatitis C virus (HCV) coinfected patients, the role of antiretroviral therapy (ART) on hepatic steatosis (HS) remains controversial. Methods HIV/HCV coinfected patients receiving ART and previously untreated for HCV who underwent a liver biopsy were included. Cumulative duration of exposure to each antiretroviral was recorded up to liver biopsy date. Logistic regression analyses evaluated factors associated with steatosis and its severity. Results 184 patients were included: median age 41years, 84% male, 89% Caucasian, 61% with a past history of intravenous drug use. HCV genotypes were 1 (55%), 2 (6%), 3 (26%), and 4 (13%). Median HCV-RNA was 6.18 log10 IU/ml. HIV-RNA was undetectable (<400 copies/ml) in 67% of patients. Median CD4 count was 321/mm3. All patients had been exposed to nucleoside reverse transcriptase inhibitors (median cumulative exposure 56months); 126 received protease inhibitors (23months), and 79 non-nucleoside reverse transcriptase inhibitors (16months). HS was observed in 102 patients (55%): 41% grade 1; 5% grade 2, and 9% grade 3. In multivariate analysis, HCV genotype 3 and HCV viral load were moderately associated with mild steatosis but strongly with grade 2-3 steatosis. After adjustment for the period of biopsy, no association was detected between HS and exposure to any antiretroviral class or drug, or duration of ART globally or comparing genotype 3 to others. Conclusions Among our ART-treated HIV-HCV cohort predominantly infected with genotype 1, 55% of patients had HS which was associated with HCV-related factors, but not ART class or duration of exposure. PMID:22490728

  6. Magnitude of adverse drug reaction and associated factors among HIV-infected adults on antiretroviral therapy in Hiwot Fana specialized university hospital, eastern Ethiopia

    PubMed Central

    Weldegebreal, Fitsum; Mitiku, Habtamu; Teklemariam, Zelalem

    2016-01-01

    Introduction Human immunodefiecency virus infected patients did not adhere correctly to their Antiretroviral Therapy because of the drugs adverse effects. Thus, continuous evaluation of the adverse effect of Antiretroviral Therapy will help to make more effective treatment. The aim of this study was to assess the prevalence of Adverse Drug Reaction and associated factors on Antiretroviral Therapy among Human immunodefiecency virus infected Adults at Hiwot Fana Specialized University Hospital, Eastern Ethiopia. Methods A Hospital based retrospective study was conducted among 358 of adult patients clinical records on antiretroviral Therapy from April1 to June30, 2014. Results The overall prevalence of Adverse Drug Reaction among Human immunodefiecency virus infected patients on antiretroviral Therapy was 17.0%. Of reported Adverse Drug Reaction, 80.3%, 18% and 1.7% occurred in patients on Stavudine, Zidovudine and Tenofovir based regimens respectively. The common Adverse Drug Reaction were lipodystrophy (fat change) (49.2%), numbness/tingling (27.9%), peripheral neuropathy (18%) and (8.2%) anaemia (8.2%). Patients on Stavudine containing regimens were more likely to develop Adverse Drug Reaction compared to Zidovudine (AOR = 0.212, 95% CI 0.167, 0.914, p<0.001) and Tenofovir (AOR=0.451, 95% CI 0.532, 0.948, p<0.001). Conclusion The overall prevalence of Adverse Drug Reaction among Human immunodefiecency virus infected patients in this study was 17% and more common on those patients taking Stavudine based regimen. Lipodystrophy and peripheral neuropathy were significantly associated with stavudine-based regimens, while anaemia was significantly associated with zidovudine based regimens. Thus regular clinical and laboratory monitoring of patients on Antiretroviral Therapy should be strengthened. PMID:27800108

  7. A Systematic Review Comparing Antiretroviral Adherence Descriptive and Intervention Studies

    PubMed Central

    Sandelowski, Margarete; Voils, Corrine I.; Chang, Yunkyung; Lee, Eun-Jeong

    2009-01-01

    We examined the extent to which studies aimed at testing interventions to improve antiretroviral adherence have targeted the facilitators of and barriers known to affect adherence. Of the 88 reports reviewed, 41 were reports of descriptive studies conducted with U.S. HIV-positive women and 47 were reports of intervention studies conducted with U.S. HIV-positive persons. We extracted from the descriptive studies all findings addressing any factor linked to antiretroviral adherence and from the intervention studies, information on the nature of the intervention, the adherence problem targeted, the persons targeted for the intervention, and the intervention outcomes desired. We discerned congruence between the prominence of substance abuse as a factor identified in the descriptive studies as a barrier to adherence and its prominence as the problem most addressed in those reports of intervention studies that specified the problems targeted for intervention. We also discerned congruence between the prominence of family and provider support as factors identified in the descriptive studies as facilitators of adherence and the presence of social support as an intervention component and outcome variable. Less discernible in the reports of intervention studies was specific attention to other factors prominent in the descriptive studies, which may be due to the complex nature of the problem, individualistic and rationalist slant of interventions, or simply the ways interventions were presented. Our review raises issues about niche standardization and intervention tailoring, targeting, and fidelity. PMID:20024751

  8. Growth and HIV-free survival of HIV-exposed infants in Malawi: A randomized trial of two complementary feeding interventions in the context of maternal antiretroviral therapy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to compare the growth of HIV-exposed children receiving 1 of 2 complementary foods after prevention of mother-to-child HIV transmission through maternal lifelong antiretroviral therapy (ART). In rural Malawi, 280 HIV-infected pregnant women were consecutively identifi...

  9. Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings

    PubMed Central

    Peterson, Kevin; Jallow, Sabelle; Rowland-Jones, Sarah L.; de Silva, Thushan I.

    2011-01-01

    HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in significant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard first-line regimens for HIV-1 in many low-income settings, have no effect on HIV-2. Nucleoside analogues alone are not sufficiently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not sufficiently effective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations. PMID:21490779

  10. Central nervous system HIV infection in "less-drug regimen" antiretroviral therapy simplification strategies.

    PubMed

    Ferretti, Francesca; Gianotti, Nicola; Lazzarin, Adriano; Cinque, Paola

    2014-02-01

    Less-drug regimens (LDR) refer to combinations of either two antiretroviral drugs or ritonavir-boosted protease inhibitor (PI) monotherapy. They may represent a simplification strategy in patients with persistently suppressed human immunodeficiency virus (HIV) viremia, with the main benefits of reducing drug-related toxicities and costs. Systemic virological efficacy of LDR is slightly lower as compared with combined antiretroviral therapy (cART), but patients with failure do not usually develop drug resistance and resuppress HIV replication after reintensification. A major concern of LDR is the lower efficacy in the virus reservoirs, especially in the central nervous system (CNS), where viral compartmentalization and independent evolution of infection may lead to CNS viral escape, often associated with neurologic symptoms. The authors reviewed studies of virological and functional CNS efficacy of LDR, particularly of boosted PI monotherapy regimens, for which more information is available. Symptomatic viral CSF escape was observed mainly in PI/r monotherapy patients with plasma failure and low nadir CD4+ cell counts, and resolved upon reintroduction of triple drug cART, whereas asymptomatic viral failure in CSF was not significantly more frequent in patients on PI/r monotherapy compared with patients on standard cART. In addition, there was no difference in functional outcomes between PI monotherapy and cART patients, irrespective of CSF viral escape. More data are needed on the CNS effect of dual ART regimens and, in general, on long-term efficacy of LDR. Simplification with LDR may be an attractive option in patients with suppressed viral load, if they are well selected and monitored for potential CNS complications.

  11. HIV Cure Strategies: How Good Must They Be to Improve on Current Antiretroviral Therapy?

    PubMed Central

    Sax, Paul E.; Sypek, Alexis; Berkowitz, Bethany K.; Morris, Bethany L.; Losina, Elena; Paltiel, A. David; Kelly, Kathleen A.; Seage, George R.; Walensky, Rochelle P.; Weinstein, Milton C.; Eron, Joseph; Freedberg, Kenneth A.

    2014-01-01

    Background We examined efficacy, toxicity, relapse, cost, and quality-of-life thresholds of hypothetical HIV cure interventions that would make them cost-effective compared to life-long antiretroviral therapy (ART). Methods We used a computer simulation model to assess three HIV cure strategies: Gene Therapy, Chemotherapy, and Stem Cell Transplantation (SCT), each compared to ART. Efficacy and cost parameters were varied widely in sensitivity analysis. Outcomes included quality-adjusted life expectancy, lifetime cost, and cost-effectiveness in dollars/quality-adjusted life year ($/QALY) gained. Strategies were deemed cost-effective with incremental cost-effectiveness ratios <$100,000/QALY. Results For patients on ART, discounted quality-adjusted life expectancy was 16.4 years and lifetime costs were $591,400. Gene Therapy was cost-effective with efficacy of 10%, relapse rate 0.5%/month, and cost $54,000. Chemotherapy was cost-effective with efficacy of 88%, relapse rate 0.5%/month, and cost $12,400/month for 24 months. At $150,000/procedure, SCT was cost-effective with efficacy of 79% and relapse rate 0.5%/month. Moderate efficacy increases and cost reductions made Gene Therapy cost-saving, but substantial efficacy/cost changes were needed to make Chemotherapy or SCT cost-saving. Conclusions Depending on efficacy, relapse rate, and cost, cure strategies could be cost-effective compared to current ART and potentially cost-saving. These results may help provide performance targets for developing cure strategies for HIV. PMID:25397616

  12. Acute hypophosphataemia and hypokalaemia in a patient starting antiretroviral therapy in Zambia-a new context for refeeding syndrome?

    PubMed

    Nyirenda, Christopher; Zulu, Isaac; Kabagambe, Edmond K; Bagchi, Shashwatee; Potter, Dara; Bosire, Claire; Krishnasami, Zipporah; Heimburger, Douglas C

    2009-01-01

    High mortality rates have been reported in the first 90 days of antiretroviral therapy in Zambia and other low-income countries. We report a case of acute hypophosphataemia and hypokalaemia in the first week of antiretroviral therapy in a patient with extreme AIDS wasting. Given its occurrence in an extremely wasted patient, it may be physiologically similar to refeeding syndrome but other causes could be relevant as well. Acute hypophosphataemia may contribute to early antiretroviral therapy associated mortality in low-income countries.

  13. Plasma Sclerostin in HIV-Infected Adults on Effective Antiretroviral Therapy.

    PubMed

    Erlandson, Kristine M; O'Riordan, MaryAnn; Hileman, Corrilynn O; Rapaport, Eric; Labbato, Danielle; Campbell, Thomas B; McComsey, Grace A

    2015-07-01

    Sclerostin is linked to bone physiology and cardiovascular disease through the Wnt/β-catenin signaling pathway. The goal of this study was to determine if sclerostin is related to bone physiology and cardiovascular disease during antiretroviral treatment in HIV-infected persons. This was a cross-sectional analysis from study entry into the Stopping Atherosclerosis and Treating Unhealthy bone with RosuvastatiN in HIV (SATURN) trial, an ongoing randomized trial comparing rosuvastatin to placebo in HIV-infected adults on antiretroviral therapy. Plasma sclerostin was measured at study entry by ELISA from participants with available samples. Spearman correlation and multivariable linear regression were used to test relationships between sclerostin and bone density or bone turnover and cardiovascular disease. Among 139 HIV-infected participants (median age 46 years, CD4 lymphocyte count 614 cells/μl), the median plasma sclerostin level was 444.1 (IQR 330.3, 570.1) pg/ml. Correlations were detected between sclerostin and age (r=0.26), lumbar spine Z-score (r=0.31), RANKL (r=-0.21), carotid intima-media thickness (CIMT, r=0.19), and sVCAM-1 (r=0.27), p<0.05. No significant correlations were detected between sclerostin and current (r=0.006) or nadir CD4 count (r=0.11). While associations between sclerostin, lumbar spine Z-score, and sVCAM-1 were robust to covariate adjustment (p<0.01), association with CIMT was no longer significant (p=0.08). Our findings provide preliminary support for a relationship between sclerostin and bone mineral density in HIV-infected persons. The Wnt/β-catenin pathway should be investigated as a potential mechanism for loss of bone mineral density in treated HIV infection. PMID:25919636

  14. Interventions for Enhancing Adherence to Antiretroviral Therapy (ART): A Systematic Review of High Quality Studies

    PubMed Central

    Sivaramalingam, Bhairavi; Navarro, Tamara; Hobson, Nicholas; Keepanasseril, Arun; Wilczynski, Nancy J.; Haynes, R. Brian

    2015-01-01

    Abstract We sought to review the effectiveness of interventions designed to improve adherence to antiretroviral therapy (ART) from studies included in a recent Cochrane review that reported a clinical and an adherence outcome, with at least 80% follow-up for 6 months or more. Data were extracted independently and in duplicate, with an adjudicator for disagreements. Risk of bias was assessed using the Cochrane Risk of Bias tool. Of 182 relevant studies in the Cochrane review, 49 were related to ART. Statistical pooling was not warranted due to heterogeneity in interventions, participants, treatments, adherence measures and outcomes. Many studies had high risk of bias in elements of design and outcome ascertainment. Only 10 studies improved both adherence and clinical outcomes. These used the following interventions: adherence counselling (two studies); a once-daily regimen (compared to twice daily); text messaging; web-based cognitive behavioral intervention; face-to-face multi-session intensive behavioral interventions (two studies); contingency management; modified directly observed therapy; and nurse-delivered home visits combined with telephone calls. Patient-related adherence interventions were the most frequently tested. Uniform adherence measures and higher quality studies of younger populations are encouraged. PMID:25825938

  15. Displacement and HIV: Factors Influencing Antiretroviral Therapy Use by Ethnic Shan Migrants in Northern Thailand.

    PubMed

    Murray, Jordan K; DiStefano, Anthony S; Yang, Joshua S; Wood, Michele M

    2016-01-01

    Migrant populations face increased HIV vulnerabilities, including limited access to antiretroviral therapy. Civil conflict in Myanmar has displaced thousands of people from the minority Shan ethnic group into northern Thailand, where they bear a disproportionate HIV burden. To identify barriers and facilitators of antiretroviral therapy use in this population, we conducted a rapid ethnographic assessment and case study with a clinical sample of Shan migrants receiving treatment for HIV in a district hospital in Chiang Mai, Thailand, Thai nurses providing their care, and health care administrators (n = 23). Barriers included fears of arrest and deportation, communication difficulties, perceived social marginalization, limited HIV knowledge, and lack of finances. Facilitating factors included hospital-based migrant registration services and community outreach efforts involving support group mobilization, referral practices, and radio broadcasts. These findings provided a contextualized account to inform policies, community interventions, and nursing practice to increase treatment access for minority migrant groups. PMID:27188762

  16. HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy

    PubMed Central

    Agosto, Luis M.; Uchil, Pradeep D.; Mothes, Walther

    2015-01-01

    The human immunodeficiency virus (HIV) spreads more efficiently in vitro when infected cells directly contact uninfected cells to form virological synapses. A hallmark of virological synapses is that viruses can be transmitted at a higher multiplicity of infection (MOI) that, in vitro, results in a higher number of proviruses. Whether HIV also spreads by cell-cell contact in vivo is a matter of debate. Here we discuss recent data that suggest that contact-mediated transmission largely manifests itself in vivo as CD4+ T cell depletion. The assault of a cell by a large number of incoming particles is likely efficiently sensed by the innate cellular surveillance to trigger cell death. The large number of particles transferred across virological synapses has also been implicated in reduced efficacy of antiretroviral therapies. Thus, antiretroviral therapies must remain effective against the high MOI observed during cell-to-cell transmission to inhibit both viral replication and the pathogenesis associated with HIV infection. PMID:25766144

  17. Genital HSV Shedding among Kenyan Women Initiating Antiretroviral Therapy

    PubMed Central

    Manguro, Griffins O.; Masese, Linnet N.; Deya, Ruth W.; Magaret, Amalia; Wald, Anna; McClelland, R. Scott; Graham, Susan M.

    2016-01-01

    Objectives Genital ulcer disease (GUD) prevalence increases in the first month of antiretroviral treatment (ART), followed by a return to baseline prevalence by month 3. Since most GUD is caused by herpes simplex virus type 2 (HSV-2), we hypothesized that genital HSV detection would follow a similar pattern after treatment initiation. Methods We conducted a prospective cohort study of 122 HSV-2 and HIV-1 co-infected women with advanced HIV disease who initiated ART and were followed closely with collection of genital swab specimens for the first three months of treatment. Results At baseline, the HSV detection rate was 32%, without significant increase in genital HSV detection noted during the first month or the third month of ART. HIV-1 shedding declined during this period; no association was also noted between HSV and HIV-1 shedding during this period. Conclusion Because other studies have reported increased HSV detection in women initiating ART and we have previously reported an increase in GUD during early ART, it may be prudent to counsel HIV-1 infected women initiating ART that HSV shedding in the genital tract may continue after ART initiation. PMID:27683204

  18. Low incidence of abacavir hypersensitivity reaction among African children initiating antiretroviral therapy.

    PubMed

    Nahirya-Ntege, Patricia; Musiime, Victor; Naidoo, Bethany; Bakeera-Kitaka, Sabrina; Nathoo, Kusum; Munderi, Paula; Mugyenyi, Peter; Kekitiinwa, Adeodata; Bwakura-Dangarembizi, Mutsa F; Crawley, Jane

    2011-06-01

    Hypersensitivity reactions are reported in approximately 5% of adults receiving abacavir, but there are few published data in children. Among 1150 African children receiving antiretroviral therapy in a randomized trial, suspected hypersensitivity reactions to abacavir were rare (0.3%; 95% CI, 0.01-0.9). Patients were managed successfully through the provision of clear guidelines and education of clinical staff, children, and their caregivers.

  19. Neuropathic and neurocongnitive complications of antiretroviral therapy among HIV-infected patients.

    PubMed

    Suvada, Jose

    2013-09-01

    The neurologic events related to antiretroviral therapy (ART) in HIV-infected ART-naive patients are relatively common. Side effects of ART and complications of HIV infection may overlap significantly. Establishing etiology of neurologic (neuropathy and neuropathic pain, changes in cognition, dementia, and myelopathy) and psychiatric (neurocognitive disorders, depression, anxiety, substance abuse and dependence, and others) complications can present a significant challenge. It has long been documented that neurologic and psychological side effects can occur with many of the agents used to treat HIV infection. Particularly, efavirenz from the non-nucleoside reverse transcriptase inhibitor (NNRTI) has been associated with neurologic and psychological complaints that may be difficult to differentiate from pre-existing mental illness, substance abuse, and HIV-related neuropsychiatric symptoms. Peripheral neuropathy (PN) of at least 6 different types is a well-known adverse effect of treatment with nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-infected patients. Lack of dealing with early stages of neurologic and psychological side effects of HIV infection and Highly Active Anti-retroviral Therapy (HAART) are observed in daily practice. The purpose of this article is to identify the neurologic, neuropsychiatric and psychiatric complications related to HIV and anti-retroviral therapy, to discuss current knowledge about these disorders, and to suggest strategies for their diagnosis and management.

  20. Advance Care Planning and HIV Infection in the Era of Antiretroviral Therapy: A Review.

    PubMed

    Sangarlangkarn, Aroonsiri; Merlin, Jessica S; Tucker, Rodney O; Kelley, Amy S

    In the era of antiretroviral therapy, HIV infection has become a chronic illness with associated multimorbidity, and practitioners are faced with an emerging population of HIV-infected patients with evolving needs for advance care planning (ACP), defined as communication between individuals and their proxies to plan for future health care decisions. This article provides a review of original research studies on ACP in HIV-infected adults in the era of antiretroviral therapy (1996-present) from PubMed, EMBASE, and PsycINFO. Eleven studies conducted between 1996 and 2015 met the selection criteria, with study sizes ranging from 9 to 2864 participants. Most studies consisted of white men in outpatient settings and had poorly defined definitions of ACP. Prevalence of ACP was variable (36%-54% had end-of-life communication, 8%-47% had advance directives). Lack of ACP was most commonly associated with low income, followed by lower severity of illness, low education level, black or Hispanic race, female sex, younger age, injection drug use, and social isolation. Practitioners reported limited time or energy and inadequate preparation or training as barriers to ACP. Existing literature on ACP in the era of antiretroviral therapy is limited, but shows that ACP prevalence in HIV-infected individuals is variable depending on socioeconomic factors, severity of illness, and practitioner resources and training. More research is needed to increase ACP among HIV-infected individuals. PMID:27398771

  1. The Impact of Non-Antiretroviral Polypharmacy on the Continuity of Antiretroviral Therapy (ART) Among HIV Patients.

    PubMed

    Krentz, Hartmut B; Gill, M John

    2016-01-01

    Improved survival achieved by many patients with HIV/AIDS has complicated their medical care as increasing numbers of co-morbidities leads to polypharmacy, increased pill burdens, and greater risks of drug-drug interactions potentially compromising antiretroviral treatment (ART). We examined the impact of non-antiretroviral polypharmacy on ART for all adults followed at the Southern Alberta Clinic, Calgary, Canada. Polypharmacy was defined as ≥5 daily medications. We compared the impact of polypharmacy on continuous (i.e., remaining on same ART for ≥6 months) vs. non-continuous (i.e., discontinuing or switching ART) ART dosing frequency, number of ART pills, number of non-ART medications, and age. Of 1190 (89.5%) patients on ART, 95% were on three-drug regimens, 63.9% on QD ART, and 62% ≥3 ART pills daily; 32.2% were experiencing polypharmacy. Polypharmacy was associated with lower CD4, AIDS, >180 months living with HIV, higher numbers of ART pills, and older age (all p < 0.01); 32.1% stopped or switched ART. Polypharmacy increased the risk for non-continuous ART (36.8% vs. 30.0%; p < 0.01). Non-continuous ART increased with daily ART pill count but not increased age. Non-adherence and adverse effects accounted for the majority of non-continuous ART. We found a strong association between polypharmacy and non-continuous ART, potentially leading to effective ART being compromised. Collaborative approaches are needed to anticipate the negative impacts of polypharmacy.

  2. Adverse drug reactions associated with antiretroviral therapy in South Africa.

    PubMed

    Birbal, Sumeshni; Dheda, Mukesh; Ojewole, Elizabeth; Oosthuizen, Frasia

    2016-09-01

    South Africa has one of the highest prevalences of HIV and AIDS in the world. HIV/AIDS patients face countless challenges, one of which is the risk of adverse drug reactions (ADRs). This study aimed to describe the ADRs reported in South Africa with reference to the type of ADRs, antiretrovirals (ARVs) implicated, seriousness of the ADRs and patient demographics associated with specific ADRs. A retrospective quantitative study was carried out using ADR reports submitted to the National Department of Health (NDoH) from 1 January 2010 to 31 December 2014. A descriptive and inferential analysis was carried out to determine the strength of the relationships between different variables. A total of 2 489 reports were analysed. This study found evidence of ADRs among patients on regimens based on stavudine (n = 1 256, 50.46%), efavirenz (n = 572, 22.98%), zidovudine (n = 209, 8.40%), tenofovir (n = 203, 8.16%) and nevirapine (n = 153, 6.15%). The 10 most common ADRs reported with the use of ARVs were peripheral neuropathy (n = 472, 19%), lipodystrophy (n = 471, 18.9%), serious skin reactions (n = 266, 10.7%), gynaecomastia (n = 219, 8.8%), renal failure (n = 140, 5.6%), dizziness (n = 133, 5.3%), hyperlactatemia (n = 118, 4.7%), psychosis/hallucinations (n = 47, 1.9%), sleep disturbances (n = 44, 1.8%) and vomiting (n = 44, 1.8%). Female patients were more likely to experience peripheral neuropathy, lipodystrophy, skin rash, anaemia and hyperlactatemia, while male patients were more prone to experience gynaecomastia and peripheral neuropathy. In addition, patients aged 30-44 years reported the most ADRs. Most reactions resulted from the use of stavudine, efavirenz, zidovudine, nevirapine and tenofovir in the population groups identified in this study. PMID:27681148

  3. Cost-Effectiveness of Tenofovir as First-Line Antiretroviral Therapy in India

    PubMed Central

    Bender, Melissa A.; Kumarasamy, Nagalingeswaran; Mayer, Kenneth H.; Wang, Bingxia; Walensky, Rochelle P.; Flanigan, Timothy; Schackman, Bruce R.; Scott, Callie A.; Lu, Zhigang; Freedberg, Kenneth A.

    2011-01-01

    Background World Health Organization guidelines for antiretroviral treatment (ART) in resource-limited settings recommend either stavudine or tenofovir as part of initial therapy. We evaluated the clinical outcomes and cost-effectiveness of first-line ART using tenofovir in India, compared to current practice using stavudine or zidovudine. Methods We used a state-transition model of HIV disease to examine strategies using different nucleoside reverse transcriptase inhibitors, combined with lamivudine and nevirapine, compared to no ART: 1) stavudine; 2) stavudine, with substitution by zidovudine after six months; 3) zidovudine; 4) tenofovir. Data were from the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India and published studies. Results Discounted mean per person survival was 36.9 months (40.1 months undiscounted) with no ART, 115.5 months (145.3) with stavudine-containing ART, 115.6 months (145.5) with stavudine and six-month zidovudine substitution, 115.7 months (145.6) with zidovudine-containing ART, and 125.9 months (162.2) with initial tenofovir. Discounted lifetime medical costs were $610 with no ART and ranged from $5,560 with stavudine-containing ART to $5,720 with zidovudine-containing ART. Initial tenofovir had an incremental cost-effectiveness ratio of $670/year of life saved compared to no ART and was more economically efficient than the other regimens. Results were most sensitive to variations in the costs of first-line tenofovir, access to additional ART after failure, mean initial CD4 count, and quality of life adjustment. Conclusions Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards, and should be considered for initial therapy for HIV-infected patients in India. PMID:20043752

  4. Population-level associations between antiretroviral therapy scale-up and all-cause mortality in South Africa.

    PubMed

    Larson, Elysia; Bendavid, Eran; Tuoane-Nkhasi, Maletela; Mbengashe, Thobile; Goldman, Thurma; Wilson, Melinda; Klausner, Jeffrey D

    2014-08-01

    Our aim was to describe the association between increasing access to antiretroviral therapy and all-cause mortality in South Africa from 2005 to 2009. We undertook a longitudinal, population-level study, using antiretroviral monitoring data reported by PEPFAR implementing partners and province-level and national all-cause mortality records from Statistics South Africa (provider of official South African government statistics) to analyse the association between antiretroviral therapy and mortality. Using mixed effects models with a random intercept for province, we estimated the contemporaneous and lagging association between antiretroviral therapy and all-cause mortality in South Africa. We also conducted subgroup analyses and estimated the number of deaths averted. For each 100 HIV-infected individuals on antiretroviral therapy reported by PEPFAR implementing partners in South African treatment programmes, there was an associated 2.9 fewer deaths that year (95% CI: 1.5, 4.2) and 6.3 fewer deaths the following year (95% CI: 4.6, 8.0). The associated decrease in mortality the year after treatment reporting was seen in both adults and children, and men and women. Treatment provided from 2005 to 2008 was associated with 28,305 deaths averted from 2006 to 2009. The scale-up of antiretroviral therapy in South Africa was associated with a significant reduction in national all-cause mortality.

  5. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with HIV in Latin America

    PubMed Central

    Duarte, Horacio A.; Harris, D. Robert; Tassiopoulos, Katherine; Leister, Erin; Negrini, Silvia Fabiana Biason de Moura; Ferreira, Flavia Faleiro; Cruz, Maria Leticia Santos; Pinto, Jorge; Allison, Susannah; Hazra, Rohan

    2016-01-01

    Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of HIV-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with HIV viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8–9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in this population. PMID:25743569

  6. CD4+ and viral load outcomes of antiretroviral therapy switch strategies after virologic failure of combination antiretroviral therapy in perinatally HIV-infected youth in the United States

    PubMed Central

    Fairlie, Lee; Karalius, Brad; Patel, Kunjal; van Dyke, Russell B.; Hazra, Rohan; Hernán, Miguel A.; Siberry, George K.; Seage, George R.; Agwu, Allison; Wiznia, Andrew

    2015-01-01

    Objective: This study compared 12-month CD4+ and viral load outcomes in HIV-infected children and adolescents with virological failure, managed with four treatment switch strategies. Design: This observational study included perinatally HIV-infected (PHIV) children in the Pediatric HIV/AIDS Cohort Study (PHACS) and Pediatric AIDS Clinical Trials (PACTG) Protocol 219C. Methods: Treatment strategies among children with virologic failure were compared: continue failing combination antiretroviral therapy (cART); switch to new cART; switch to drug-sparing regimen; and discontinue all ART. Mean changes in CD4+% and viral load from baseline (time of virologic failure) to 12 months follow-up in each group were evaluated using weighted linear regression models. Results: Virologic failure occurred in 939 out of 2373 (40%) children. At 12 months, children switching to new cART (16%) had a nonsignificant increase in CD4+% from baseline, 0.59 percentage points [95% confidence interval (95% CI) −1.01 to 2.19], not different than those who continued failing cART (71%) (−0.64 percentage points, P = 0.15) or switched to a drug-sparing regimen (5%) (1.40 percentage points, P = 0.64). Children discontinuing all ART (7%) experienced significant CD4+% decline −3.18 percentage points (95% CI −5.25 to −1.11) compared with those initiating new cART (P = 0.04). All treatment strategies except discontinuing ART yielded significant mean decreases in log10VL by 12 months, the new cART group having the largest drop (−1.15 log10VL). Conclusion: In PHIV children with virologic failure, switching to new cART was associated with the best virological response, while stopping all ART resulted in the worst immunologic and virologic outcomes and should be avoided. Drug-sparing regimens and continuing failing regimens may be considered with careful monitoring. PMID:26182197

  7. High levels of Zinc-α-2-Glycoprotein among Omani AIDS patients on combined antiretroviral therapy

    PubMed Central

    Hasson, Sidgi Syed Anwer; Al-Balushi, Mohammed Saeed; Al Yahmadi, Muzna Hamed; Al-Busaidi, Juma Zaid; Said, Elias Antony; Othman, Mohammed Shafeeq; Sallam, Talal Abdullah; Idris, Mohammed Ahmad; Al-Jabri, Ali Abdullah

    2014-01-01

    Objective To investigate the levels of zinc-α-2-glycoprotein (ZAG) among Omani AIDS patients receiving combined antiretroviral therapy (cART). Methods A total of 80 Omani AIDS patients (45 males and 35 females), average age of 36 years, who were receiving cART at the Sultan Qaboos University Hospital (SQUH), Muscat, Oman, were tested for the levels of ZAG. In addition, 80 healthy blood donors (46 males and 34 females), average age of 26 years, attending the SQUH Blood Bank, were tested in parallel as a control group. Measurement of the ZAG levels was performed using a competitive enzyme-linked immunosorbent assay and in accordance with the manufacturer's instructions. Results The ZAG levels were found to be significantly higher among AIDS patients compared to the healthy individuals (P=0.033). A total of 56 (70%) of the AIDS patients were found to have higher levels of ZAG and 16 (20%) AIDS patients were found to have high ZAG levels, which are significantly (P>0.031) associated with weight loss. Conclusions ZAG levels are high among Omani AIDS patients on cART and this necessitates the measurement of ZAG on routine basis, as it is associated with weight loss. PMID:25183329

  8. Tailored nutrition education and food assistance improve adherence to HIV antiretroviral therapy: evidence from Honduras.

    PubMed

    Martinez, Homero; Palar, Kartika; Linnemayr, Sebastian; Smith, Alexandria; Derose, Kathryn Pitkin; Ramírez, Blanca; Farías, Hugo; Wagner, Glenn

    2014-10-01

    Food insecurity and malnutrition negatively affect adherence to antiretroviral therapy (ART) and are associated with poor HIV clinical outcomes. We examined the effect of providing household food assistance and nutrition education on ART adherence. A 12-month prospective clinical trial compared the effect of a monthly household food basket (FB) plus nutrition education (NE) versus NE alone on ART adherence on 400 HIV patients at four clinics in Honduras. Participants had been receiving ART for an average of 3.7 years and were selected because they had suboptimal adherence. Primary outcome measures were missed clinic appointments, delayed prescription refills, and self-reported missed doses of ART. These three adherence measures improved for both groups over 12 months (p < 0.01), mostly within 6 months. On-time prescription refills improved for the FB plus NE group by 19.6 % more than the group receiving NE alone after 6 months (p < 0.01), with no further change at 12 months. Change in missed appointments and self-reported missed ART doses did not significantly differ by intervention group.

  9. Correlates of Antiretroviral Therapy Adherence among HIV-Infected Older Adults

    PubMed Central

    McCoy, Katryna; Waldrop-Valverde, Drenna; Balderson, Benjamin H.; Mahoney, Christine; Catz, Sheryl

    2016-01-01

    Background Despite the success of antiretroviral therapy (ART), HIV-infected older African Americans experience higher mortality rates compared to their white counterparts. This disparity may be partly attributable to the differences in ART adherence by different racial and gender groups. The purpose of this study was to describe demographic, psychosocial, and HIV disease-related factors that influence ART adherence and to determine whether race and gender impact ART adherence among HIV-infected adults aged 50 years and older. Methods This descriptive study involved a secondary analysis of baseline data from 426 participants in “PRIME,” a telephone-based ART adherence and quality-of-life intervention trial. Logistic regression was used to examine the association between independent variables and ART adherence. Results Higher annual income and increased self-efficacy were associated with being ≥95% ART adherent. Race and gender were not associated with ART adherence. Conclusion These findings indicated that improvements in self-efficacy for taking ART may be an effective strategy to improve adherence regardless of race or gender. PMID:27071744

  10. Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy

    PubMed Central

    Rizzardi, G. Paolo; Harari, Alexandre; Capiluppi, Brunella; Tambussi, Giuseppe; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Chave, Jean-Philippe; Lazzarin, Adriano; Pantaleo, Giuseppe

    2002-01-01

    Primary HIV-1 infection causes extensive immune activation, during which CD4+ T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4+ T cell levels, both in terms of percentage and absolute numbers. The increase in CD4+ T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8+ or CD4+ T cell responses. At week 48, the proportion of IFN-γ–secreting CD4+ and CD4+CCR7– T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection. PMID:11877476

  11. HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

    PubMed Central

    Morse, Caryn G.; Voss, Joachim G.; Rakocevic, Goran; McLaughlin, Mary; Vinton, Carol L.; Huber, Charles; Hu, Xiaojun; Yang, Jun; Huang, Da Wei; Logun, Carolea; Danner, Robert L.; Rangel, Zoila G.; Munson, Peter J.; Orenstein, Jan M.; Rushing, Elisabeth J.; Lempicki, Richard A.; Dalakas, Marinos C.; Kovacs, Joseph A.

    2012-01-01

    Background. Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Methods. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)–based ART, and HIV-negative controls. Results. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+/HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. Conclusions. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART. PMID:22476717

  12. Maximizing the benefits of antiretroviral therapy for key affected populations

    PubMed Central

    Grubb, Ian R; Beckham, Sarah W; Kazatchkine, Michel; Thomas, Ruth M; Albers, Eliot R; Cabral, Mauro; Lange, Joep; Vella, Stefano; Kurian, Manoj; Beyrer, Chris

    2014-01-01

    Introduction Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services. Discussion Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed. Conclusions Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm

  13. The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy

    PubMed Central

    Wyatt, Christina M.; Morgello, Susan; Katz-Malamed, Rebecca; Wei, Catherine; Klotman, Mary E.; Klotman, Paul E.; D’Agati, Vivette D.

    2009-01-01

    With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal pathology found in a prospective cohort of antiretroviral-experienced patients (the Manhattan HIV Brain Bank) who had consented to postmortem organ donation. Nearly one-third of 89 kidney tissue donors had chronic kidney disease, and evidence of some renal pathology was found in 75. The most common diagnoses were arterionephrosclerosis, HIV-associated nephropathy and glomerulonephritis. Other diagnoses included pyelonephritis, interstitial nephritis, diabetic nephropathy, fungal infection and amyloidosis. Excluding 2 instances of acute tubular necrosis, slightly over one-third of the cases would have been predicted using current diagnostic criteria for chronic kidney disease. Based on semi-quantitative analysis of stored specimens, pre-mortem microalbuminuria testing could have identified an additional 12 cases. Future studies are needed to evaluate the cost-effectiveness of more sensitive methods for defining chronic kidney disease, in order to identify HIV-infected patients with early kidney disease who may benefit from antiretroviral therapy and other interventions known to delay disease progression and prevent complications. PMID:19052538

  14. Adherence to HIV/AIDS antiretroviral therapy among drug users: A qualitative study in Iran

    PubMed Central

    Hosseini, Zahra; Eftkhar, Hasan; Nedjat, Saharnaz; Ebadi, Abbas; Abbasian, Ladan; Zamani, Fereshte; Aghamollaei, Teamur; Shojaeizade, Davood

    2016-01-01

    Background: The introduction of antiretroviral therapy has caused a remarkable decrease in the occurrence of diseases and mortality among HIV-positive patients, while this success has not been achieved among injection addicts due to a low adherence to antiretroviral medicine. This study aims at clarifying the important factors affecting adherence to treatment in addicts suffering from HIV. Materials and Methods: In this qualitative research, data were gathered through in-depth interviews and field notes, and were interpreted through content analysis in the form of constant comparison. The participants were 16 drug addicts living with HIV/AIDS. Most of them had records of imprisonment and were receiving Highly Active Antiretroviral Therapy (HAART) drug treatments in the AIDS center of Imam Khomeini Hospital complex, affiliated to Tehran University of Medical Sciences. Sampling was started in a purposive method and was continued until data were saturated. Results: Four main categories including psychological reactions, contradictory beliefs, perceived support, and individual and environmental barriers were extracted from the data, each having some sub-categories. Conclusions: The obtained results indicated that adherence to the treatment of HIV is not constant and mono-dimensional, but is a function of different factors. Hence, an individual having feeble adherence in a specific time and under specific circumstances may show desirable adherence under a different circumstance. Thus, treatment of addicts living with HIV/AIDS requires physical, psychological, and social attention along with drug treatments. PMID:26985220

  15. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics

    PubMed Central

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-01-01

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  16. Can antiretroviral therapy be tailored to each human immunodeficiency virus-infected individual? Role of pharmacogenomics.

    PubMed

    Asensi, Victor; Collazos, Julio; Valle-Garay, Eulalia

    2015-08-12

    Pharmacogenetics refers to the effect of single nucleotide polymorphisms (SNPs) within human genes on drug therapy outcome. Its study might help clinicians to increase the efficacy of antiretroviral drugs by improving their pharmacokinetics and pharmacodynamics and by decreasing their side effects. HLAB*5701 genotyping to avoid the abacavir-associated hypersensitivity reaction (HSR) is a cost-effective diagnostic tool, with a 100% of negative predictive value, and, therefore, it has been included in the guidelines for treatment of human immunodeficiency virus (HIV) infection. HALDRB*0101 associates with nevirapine-induced HSR. CYP2B6 SNPs modify efavirenz plasma levels and their genotyping help decreasing its central nervous system, hepatic and HSR toxicities. Cytokines SNPs might influence the development of drug-associated lipodystrophy. APOA5, APOB, APOC3 and APOE SNPs modify lipids plasma levels and might influence the coronary artery disease risk of HIV-infected individuals receiving antiretroviral therapy. UGT1A1*28 and ABCB1 (MDR1) 3435C > T SNPs modify atazanavir plasma levels and enhance hyperbilirubinemia. Much more effort needs to be still devoted to complete large prospective studies with multiple SNPs genotyping in order to reveal more clues about the role played by host genetics in antiretroviral drug efficacy and toxicity. PMID:26279978

  17. Annual cost of antiretroviral therapy among three service delivery models in Uganda

    PubMed Central

    Vu, Lung; Waliggo, Samuel; Zieman, Brady; Jani, Nrupa; Buzaalirwa, Lydia; Okoboi, Stephen; Okal, Jerry; Borse, Nagesh N; Kalibala, Samuel

    2016-01-01

    Introduction In response to the increasing burden of HIV, the Ugandan government has employed different service delivery models since 2004 that aim to reduce costs and remove barriers to accessing HIV care. These models include community-based approaches to delivering antiretroviral therapy (ART) and delegating tasks to lower-level health workers. This study aimed to provide data on annual ART cost per client among three different service delivery models in Uganda. Methods Costing data for the entire year 2012 were retrospectively collected as part of a larger task-shifting study conducted in three organizations in Uganda: Kitovu Mobile (KM), the AIDS Support Organisation (TASO) and Uganda Cares (UC). A standard cost data capture tool was developed and used to retrospectively collect cost information regarding antiretroviral (ARV) drugs and non-ARV drugs, ART-related lab tests, personnel and administrative costs. A random sample of four TASO centres (out of 11), four UC clinics (out of 29) and all KM outreach units were selected for the study. Results Cost varied across sites within each organization as well as across the three organizations. In addition, the number of annual ART visits was more frequent in rural areas and through KM (the community distribution model), which played a major part in the overall annual ART cost. The annual cost per client (in USD) was $404 for KM, $332 for TASO and $257 for UC. These estimates were lower than previous analyses in Uganda or the region compared to data from 2001 to 2009, but comparable with recent estimates using data from 2010 to 2013. ARVs accounted for the majority of the total cost, followed by personnel and operational costs. Conclusions The study provides updated data on annual cost per ART visit for three service delivery models in Uganda. These data will be vital for in-country budgetary efforts to ensure that universal access to ART, as called for in the 2015 World Health Organization (WHO) guidelines, is

  18. Hybrid data capture for monitoring patients on highly active antiretroviral therapy (HAART) in urban Botswana.

    PubMed Central

    Bussmann, Hermann; Wester, C. William; Ndwapi, Ndwapi; Vanderwarker, Chris; Gaolathe, Tendani; Tirelo, Geoffrey; Avalos, Ava; Moffat, Howard; Marlink, Richard G.

    2006-01-01

    Individual patient care and programme evaluation are pivotal for the success of antiretroviral treatment programmes in resource-limited countries. While computer-aided documentation and data storage are indispensable for any large programme, several important issues need to be addressed including which data are to be collected, who collects it and how it is entered into an electronic database. We describe a patient-monitoring approach, which uses patient encounter forms (in hybrid paper + electronic format) based on optical character recognition, piloted at Princess Marina Hospital in Gaborone, Botswana's first public highly active antiretroviral therapy (HAART) outpatient clinic. Our novel data capture approach collects "key" data for tracking patient and programme outcomes. It saves physician time and does not detract from clinical care. PMID:16501730

  19. Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

    PubMed Central

    May, Margaret T.; Vehreschild, Janne; Obel, Niels; Gill, Michael John; Crane, Heidi; Boesecke, Christoph; Samji, Hasina; Grabar, Sophie; Cazanave, Charles; Cavassini, Matthias; Shepherd, Leah; d’Arminio Monforte, Antonella; Smit, Colette; Saag, Michael; Lampe, Fiona; Hernando, Vicky; Montero, Marta; Zangerle, Robert; Justice, Amy C.; Sterling, Timothy; Miro, Jose; Ingle, Suzanne; Sterne, Jonathan A. C.

    2016-01-01

    Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes. PMID:27525413

  20. Neuromuscular complications of human immunodeficiency virus infection and antiretroviral therapy.

    PubMed Central

    Miller, R G

    1994-01-01

    At least 4 distinct peripheral neuropathy syndromes occur in patients infected with the human immunodeficiency virus. The most common, painful sensory neuropathy, may be related to the viral infection or may be medication induced and is treated symptomatically. The other 3, chronic inflammatory demyelinating polyradiculoneuropathy, mononeuropathy multiplex (some patients), and the progressive polyradiculopathies related to the acquired immunodeficiency syndrome, may all respond to appropriate therapy. Both inflammatory myopathy and zidovudine myopathy also abate with early diagnosis and treatment. PMID:8048229

  1. Patient attrition from the HIV antiretroviral therapy program at two hospitals in Haiti

    PubMed Central

    Puttkammer, Nancy H.; Zeliadt, Steven B.; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Coq, Nancy Rachel Labbé; Raphael, Nernst Atwood; Sherr, Kenneth; Tegger, Mary; Yuhas, Krista; Barnhart, Scott

    2016-01-01

    Objective To identify factors associated with antiretroviral therapy (ART) attrition among patients initiating therapy in 2005–2011 at two large, public-sector department-level hospitals, and to inform interventions to improve ART retention. Methods This retrospective cohort study used data from the iSanté electronic medical record (EMR) system. The study characterized ART attrition levels and explored the patient demographic, clinical, temporal, and service utilization factors associated with ART attrition, using time-to-event analysis methods. Results Among the 2 023 patients in the study, ART attrition on average was 17.0 per 100 person-years (95% confidence interval (CI): 15.8–18.3). In adjusted analyses, risk of ART attrition was up to 89% higher for patients living in distant communes compared to patients living in the same commune as the hospital (hazard ratio: 1.89, 95%CI: 1.54–2.33; P < 0.001). Hospital site, earlier year of ART start, spending less time enrolled in HIV care prior to ART initiation, receiving a non-standard ART regimen, lacking counseling prior to ART initiation, and having a higher body mass index were also associated with attrition risk. Conclusions The findings suggest quality improvement interventions at the two hospitals, including: enhanced retention support and transportation subsidies for patients accessing care from remote areas; counseling for all patients prior to ART initiation; timely outreach to patients who miss ART pick-ups; “bridging services” for patients transferring care to alternative facilities; routine screening for anticipated interruptions in future ART pick-ups; and medical case review for patients placed on non-standard ART regimens. The findings are also relevant for policymaking on decentralization of ART services in Haiti. PMID:25563149

  2. Food Insecurity, Dietary Diversity, and Body Mass Index of HIV-Infected Individuals on Antiretroviral Therapy in Rural Haiti.

    PubMed

    Rebick, Gabriel W; Franke, Molly F; Teng, Jessica E; Gregory Jerome, J; Ivers, Louise C

    2016-05-01

    Food rations are increasingly offered as part of HIV programs in resource-poor settings, often targeted solely to those with under-nutrition by low body mass index (BMI). This practice does not consider food insecurity, another important risk factor for poor outcomes in people living with HIV/AIDS (PLWH). We analyzed factors associated with low BMI and severe food insecurity in 523 PLWH receiving antiretroviral therapy in rural Haiti using logistic regression. Food insecurity was present in 89 % of individuals. Among those with severe food insecurity, 86 % had a BMI ≥ 18.5 kg/m(2). Severe food insecurity was associated with illiteracy [adjusted odds ratio (AOR) 1.79, p = 0.005], having no income (AOR 1.58, p = 0.04), and poverty (p < 0.001). Compared with those with little to no food insecurity, individuals with severe food insecurity had a less diverse diet. We found that food insecurity was highly prevalent in PLWH receiving antiretroviral therapy in rural Haiti. Using BMI as a sole criterion for food supplementation in HIV programs can exclude highly vulnerable individuals who may benefit from such support.

  3. Novel Codon Insert in HIV Type 1 Clade B Reverse Transcriptase Associated with Low-Level Viremia During Antiretroviral Therapy

    PubMed Central

    Gianella, Sara; Vazquez, Homero; Ignacio, Caroline; Zweig, Adam C.; Richman, Douglas D.; Smith, Davey M.

    2014-01-01

    Abstract We investigated the pol genotype in two phylogenetically and epidemiologically linked partners, who were both experiencing persistent low-level viremia during antiretroviral therapy. In one partner we identified a new residue insertion between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding region (HXB2 numbering). We then investigated the potential impact of identified mutations in RT and antiretroviral binding affinity using a novel computational approach. PMID:24020934

  4. Discontinuation of Initial Antiretroviral Therapy in Clinical Practice: Moving Toward Individualized Therapy

    PubMed Central

    Di Biagio, Antonio; Cozzi-Lepri, Alessandro; Angarano, Gioacchino; Gori, Andrea; Quirino, Tiziana; De Luca, Andrea; Costantini, Andrea; Mussini, Cristina; Rizzardini, Giuliano; Castagna, Antonella; Antinori, Andrea; d'Arminio Monforte, Antonella

    2016-01-01

    Background: Study aim was to estimate the rate and identify predictors of discontinuation of first combination antiretroviral therapy (cART) in recent years. Methods: Patients who initiated first cART between January 2008 and October 2014 were included. Discontinuation was defined as stop of at least 1 drug of the regimen, regardless of the reason. All causes of discontinuation were evaluated and 3 main endpoints were considered: toxicity, intolerance, and simplification. Predictors of discontinuation were examined separately for all 3 endpoints. Kaplan–Meier analysis was used for the outcome discontinuation of ≥1 drug regardless of the reason. Cox regression analysis was used to identify factors associated with treatment discontinuation because of the 3 reasons considered. Results: A total of 4052 patients were included. Main reason for stopping at least 1 drug were simplification (29%), intolerance (21%), toxicity (19%), other causes (18%), failure (8%), planned discontinuation (4%), and nonadherence (2%). In a multivariable Cox model, predictors of discontinuation for simplification were heterosexual transmission (P = 0.007), being immigrant (P = 0.017), higher nadir lymphocyte T CD4+ cell (P = 0.011), and higher lymphocyte T CD8+ cell count (P = 0.025); for discontinuation due to intolerance: the use of statins (P = 0.029), higher blood glucose levels (P = 0.050). About toxicity: higher blood glucose levels (P = 0.010) and the use of zidovudine/lamivudine as backbone (P = 0.044). Conclusions: In the late cART era, the main reason for stopping the initial regimen is simplification. This scenario reflects the changes in recommendations aimed to enhance adherence and quality of life, and minimize drug toxicity. PMID:26871881

  5. Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy

    PubMed Central

    Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho

    2016-01-01

    Objectives To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. Method This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The “Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral” (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Results Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. Conclusion A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test. PMID:27695297

  6. Loss to Clinic and Five-Year Mortality among HIV-Infected Antiretroviral Therapy Initiators

    PubMed Central

    Edwards, Jessie K.; Cole, Stephen R.; Westreich, Daniel; Moore, Richard; Mathews, Christopher; Geng, Elvin; Eron, Joseph J.; Mugavero, Michael J.

    2014-01-01

    Missing outcome data due to loss to follow-up occurs frequently in clinical cohort studies of HIV-infected patients. Censoring patients when they become lost can produce inaccurate results if the risk of the outcome among the censored patients differs from the risk of the outcome among patients remaining under observation. We examine whether patients who are considered lost to follow up are at increased risk of mortality compared to those who remain under observation. Patients from the US Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who newly initiated combination antiretroviral therapy between January 1, 1998 and December 31, 2009 and survived for at least one year were included in the study. Mortality information was available for all participants regardless of continued observation in the CNICS. We compare mortality between patients retained in the cohort and those lost-to-clinic, as commonly defined by a 12-month gap in care. Patients who were considered lost-to-clinic had modestly elevated mortality compared to patients who remained under observation after 5 years (risk ratio (RR): 1.2; 95% CI: 0.9, 1.5). Results were similar after redefining loss-to-clinic as 6 months (RR: 1.0; 95% CI: 0.8, 1.3) or 18 months (RR: 1.2; 95% CI: 0.8, 1.6) without a documented clinic visit. The small increase in mortality associated with becoming lost to clinic suggests that these patients were not lost to care, rather they likely transitioned to care at a facility outside the study. The modestly higher mortality among patients who were lost-to-clinic implies that when we necessarily censor these patients in studies of time-varying exposures, we are likely to incur at most a modest selection bias. PMID:25010739

  7. Self-perception of knowledge and adherence reflecting the effectiveness of antiretroviral therapy

    PubMed Central

    Dagli-Hernandez, Carolina; Lucchetta, Rosa Camila; de Nadai, Tales Rubens; Galduróz, José Carlos Fernandez; Mastroianni, Patricia de Carvalho

    2016-01-01

    Objectives To evaluate which indirect method for assessing adherence best reflects highly active antiretroviral therapy (HAART) effectiveness and the factors related to adherence. Method This descriptive, cross-sectional study was performed in 2012 at a reference center of the state of São Paulo. Self-report (simplified medication adherence questionnaire [SMAQ]) and drug refill parameters were compared to the viral load (clinical parameter of the effectiveness of pharmacotherapy [EP]) to evaluate the EP. The “Cuestionario para la Evaluación de la Adhesión al Tratamiento Antiretroviral” (CEAT-VIH) was used to evaluate factors related to adherence and the EP and, complementarily, patient self-perception of adherence was compared to the clinical parameter of the EP. Results Seventy-five patients were interviewed, 60 of whom were considered as adherent from the clinical parameter of the EP and ten were considered as adherent from all parameters. Patient self-perception about adherence was the instrument that best reflected the EP when compared to the standardized self-report questionnaire (SMAQ) and drug refill parameter. The level of education and the level of knowledge on HAART were positively correlated to the EP. Forgetfulness, alcohol use, and lack of knowledge about the medications were the factors most frequently reported as a cause of nonadherence. Conclusion A new parameter of patient self-perception of adherence, which is a noninvasive, inexpensive instrument, could be applied and assessed as easily as self-report (SMAQ) during monthly drug refill, since it allows monitoring adherence through pharmaceutical assistance. Therefore, patient adherence to HAART could be evaluated using self-perception (CEAT-VIH) and the viral load test.

  8. Dynamics of the HIV infection under antiretroviral therapy: A cellular automata approach

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; Coutinho, Sérgio; Zorzenon dos Santos, Rita Maria; de Figueirêdo, Pedro Hugo

    2013-10-01

    The dynamics of human immunodeficiency virus infection under antiretroviral therapy is investigated using a cellular automata model where the effectiveness of each drug is self-adjusted by the concentration of CD4+ T infected cells present at each time step. The effectiveness of the drugs and the infected cell concentration at the beginning of treatment are the control parameters of the cell population’s dynamics during therapy. The model allows describing processes of mono and combined therapies. The dynamics that emerges from this model when considering combined antiretroviral therapies reproduces with fair qualitative agreement the phases and different time scales of the process. As observed in clinical data, the results reproduce the significant decrease in the population of infected cells and a concomitant increase of the population of healthy cells in a short timescale (weeks) after the initiation of treatment. Over long time scales, early treatment with potent drugs may lead to undetectable levels of infection. For late treatment or treatments starting with a low density of CD4+ T healthy cells it was observed that the treatment may lead to a steady state in which the T cell counts are above the threshold associated with the onset of AIDS. The results obtained are validated through comparison to available clinical trial data.

  9. Associations among the use of highly active antiretroviral therapy, oral candidiasis, oral Candida species and salivary immunoglobulin A in HIV-infected children

    PubMed Central

    Pomarico, Luciana; Ferraz Cerqueira, Daniella; de Araujo Soares, Rosangela Maria; Ribeiro de Souza, Ivete Pomarico; Barbosa de Araujo Castro, Gloria Fernanda; Socransky, Sigmund; Haffajee, Anne; Palmier Teles, Ricardo

    2009-01-01

    Objectives To examine the impact of antiretroviral therapy on the prevalence of oral candidiasis, recovery of oral Candida species (spp) and salivary levels of total secretory immunoglobulin A (SIgA) and Candida-specific SIgA in human immunodeficiency virus (HIV)-infected children. Methods Sixty six HIV-positive and 40 HIV-negative children were cross-sectionally examined for the presence of oral lesions. Whole stimulated saliva samples were collected for the identification of Candida spp using culture and measurement of total and specific SIgA using enzyme-linked immunosorbent assay (ELISA). Results HIV-positive children had a higher prevalence of oral candidiasis (p < 0.05); higher frequency of detection of Candida spp (p < 0.05) and higher levels of total (p < 0.05) and Candida-specific SIgA (p < 0.001) than did HIV-negative children. Among HIV-positive subjects, antiretroviral users had lower viral loads (p < 0.001), lower levels of Candida spp (p < 0.05) and total SIgA (p < 0.05) compared with antiretroviral non-users. Conclusions The use of antiretroviral therapy was associated with decreases in the prevalence of oral candidiasis. This diminished exposure to Candida spp was accompanied by decreases in levels of total and Candida-specific SIgA. PMID:19615660

  10. Antiretroviral therapy CNS penetration and HIV-1–associated CNS disease

    PubMed Central

    Winston, A.; Walsh, J.; Post, F.; Porter, K.; Gazzard, B.; Fisher, M.; Leen, C.; Pillay, D.; Hill, T.; Johnson, M.; Gilson, R.; Anderson, J.; Easterbrook, P.; Bansi, L.; Orkin, C.; Ainsworth, J.; Palfreeman, A.; Gompels, M.; Phillips, A.N.; Sabin, C.A.

    2011-01-01

    Objective: The impact of different antiretroviral agents on the risk of developing or surviving CNS disease remains unknown. The aim of this study was to investigate whether using antiretroviral regimens with higher CNS penetration effectiveness (CPE) scores was associated with reduced incidence of CNS disease and improved survival in the UK Collaborative HIV Cohort (CHIC) Study. Methods: Adults without previous CNS disease, who commenced combination antiretroviral therapy (cART) between 1996 and 2008, were included (n = 22,356). Initial and most recent cART CPE scores were calculated. CNS diseases were HIV encephalopathy (HIVe), progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis (TOXO), and cryptococcal meningitis (CRYPTO). Incidence rates and overall survival were stratified by CPE score. A multivariable Poisson regression model was used to identify independent associations. Results: The median (interquartile range) CPE score for initial cART regimen increased from 7 (5–8) in 1996–1997 to 9 (8–10) in 2000–2001 and subsequently declined to 6 (7–8) in 2006–2008. Differences in gender, HIV acquisition risk group, and ethnicity existed between CPE score strata. A total of 251 subjects were diagnosed with a CNS disease (HIVe 80; TOXO 59; CRYPTO 56; PML 54). CNS diseases occurred more frequently in subjects prescribed regimens with CPE scores ≤4, and less frequently in those with scores ≥10; however, these differences were nonsignificant. Initial and most recent cART CPE scores ≤4 were independently associated with increased risk of death. Conclusion: Clinical status at time of commencing cART influences antiretroviral selection and CPE score. This information should be considered when utilizing CPE scores for retrospective analyses. PMID:21339496

  11. Outcomes of antiretroviral therapy among younger versus older adolescents and adults in an urban clinic, Zimbabwe

    PubMed Central

    Takarinda, K. C.; Owiti, P.; Mutasa-Apollo, T.; Mugurungi, O.; Buruwe, L.; Reid, A. J.

    2016-01-01

    Setting: A non-governmental organisation-supported clinic offering health services including antiretroviral therapy (ART). Objective: To compare ART retention between younger (age 10–14 years) vs. older (age 15–19 years) adolescents and younger (age 20–29 years) vs. older (age ⩾30 years) adults and determine adolescent- and adult-specific attrition-associated factors among those initiated on ART between 2010 and 2011. Design: Retrospective cohort study. Results: Of 110 (7%) adolescents and 1484 (93%) adults included in the study, no differences in retention were observed between younger vs. older adolescents at 6, 12 and 24 months. More younger adolescents were initiated with body mass index <16 kg/m2 compared with older adolescents (64% vs. 47%; P = 0.04). There were more females (74% vs. 52%, P < 0.001) and fewer patients initiating ART with CD4 count ⩽350 cells/mm3 (77% vs. 81%, P = 0.007) among younger vs. older adults. Younger adults demonstrated more attrition than older adults at all time-points. No attrition risk factors were observed among adolescents. Attrition-associated factors among adults included being younger, having a lower CD4 count and advanced human immunodeficiency virus disease at initiation, and initiation on a stavudine-based regimen. Conclusion: Younger adults demonstrated greater attrition and may require more attention. We were unable to demonstrate differences in attrition among younger vs. older adolescents. Loss to follow-up was the main reason for attrition across all age groups. Overall, earlier presentation for ART care appears important for improved ART retention among adults. PMID:27358802

  12. Clinical Outcome of HIV-Infected Patients with Discordant Virological and Immunological Response to Antiretroviral Therapy

    PubMed Central

    Zoufaly, A.; an der Heiden, M.; Kollan, C.; Bogner, J. R.; Fätkenheuer, G.; Wasmuth, J. C.; Stoll, M.; Hamouda, O.

    2011-01-01

    Background. A subgroup of human immunodeficiency virus type 1 (HIV-1)–infected patients with severe immunodeficiency show persistently low CD4+ cell counts despite sustained viral suppression. It is unclear whether this immuno-virological discordance translates into an increased risk for clinical events. Methods. Data analysis from a large multicenter cohort incorporating 14,433 HIV-1–infected patients in Germany. Treatment-naive patients beginning antiretroviral therapy (ART) with CD4+ cell counts <200 cells/μL who achieved complete and sustained viral suppression <50 copies/mL (n = 1318) were stratified according to the duration of immuno-virological discordance (failure to achieve a CD4+ cell count ≥200 cells/μL). Groups were compared by descriptive and Poisson statistics. The time-varying discordance status was analyzed in a multivariable Cox model. Results. During a total of 5038 person years of follow-up, 42 new AIDS events occurred. The incidence rate of new AIDS events was highest in the initial 6 months of complete viral suppression (immuno-virological discordance group, 55.06; 95% confidence interval [CI], 30.82–90.82; and immune responder group, 24.54; 95% CI, 10.59–48.35) and decreased significantly by 65% per year in patients with immuno-virological discordance (incidence risk ratio, 0.35; 95% CI, 0.14–0.92; P = .03). Immuno-virological discordance and prior AIDS diagnosis were independently associated with new AIDS events (hazard ratio, 3.10; 95% CI, 1.09–8.82; P = .03). Conclusion. Compared with immune responders, patients with immuno-virological discordance seem to remain at increased risk for AIDS. Absolute risk is greatly reduced after the first 6 months of complete viral suppression. PMID:21208929

  13. T-Cell Subsets Predict Mortality in Malnourished Zambian Adults Initiating Antiretroviral Therapy

    PubMed Central

    Chisenga, Caroline C.; Filteau, Suzanne; Siame, Joshua; Chisenga, Molly; Prendergast, Andrew J.; Kelly, Paul

    2015-01-01

    Objective To estimate the prognostic value of T-cell subsets in Zambian patients initiating antiretroviral therapy (ART), and to assess the impact of a nutritional intervention on T-cell subsets. Methods This was a sub-study of a randomised clinical trial of a nutritional intervention for malnourished adults initiating ART. Participants in a randomised controlled trial (NUSTART trial) were enrolled between April and December 2012. Participants received lipid-based nutritional supplement either with or without additional vitamins and minerals. Immunophenotyping was undertaken at baseline and, in survivors, after 12 weeks of ART to characterize T-cell subsets using the markers CD3, CD4, CD8, CD45RA, CCR7, CD28, CD57, CD31, α4β7, Ki67, CD25 and HLA-DR. Univariate and multivariate survival analysis was performed, and responses to treatment were analysed using the Wicoxon rank-sum test. Results Among 181 adults, 36 (20%) died by 12 weeks after starting ART. In univariate analysis, patients who died had fewer proliferating, more naïve and fewer gut homing CD4+ T-cells compared to survivors; and more senescent and fewer proliferating CD8+ T-cells. In a multivariate Cox regression model high naïve CD4+, low proliferating CD4+, high senescent CD8+ and low proliferating CD8+ subsets were independently associated with increased risk of death. Recent CD4+ thymic emigrants increased less between recruitment and 12 weeks of ART in the intervention group compared to the control group. Conclusions Specific CD4+ T-cell subsets are of considerable prognostic significance for patients initiating ART in Zambia, but only thymic output responded to this nutritional intervention. PMID:26083409

  14. Cost-effectiveness of anti-retroviral therapy at a district hospital in southern Ethiopia

    PubMed Central

    Bikilla, Asfaw Demissie; Jerene, Degu; Robberstad, Bjarne; Lindtjørn, Bernt

    2009-01-01

    Background As the resource implications of expanding anti-retroviral therapy (ART) are likely to be large, there is a need to explore its cost-effectiveness. So far, there is no such information available from Ethiopia. Objective To assess the cost-effectiveness of ART for routine clinical practice in a district hospital setting in Ethiopia. Methods We estimated the unit cost of HIV-related care from the 2004/5 fiscal year expenditure of Arba Minch Hospital in southern Ethiopia. We estimated outpatient and inpatient service use from HIV-infected patients who received care and treatment at the hospital between January 2003 and March 2006. We measured the health effect as life years gained (LYG) for patients receiving ART compared with those not receiving such treatment. The study adopted a health care provider perspective and included both direct and overhead costs. We used Markov model to estimate the lifetime costs, health benefits and cost-effectiveness of ART. Findings ART yielded an undiscounted 9.4 years expected survival, and resulted in 7.1 extra LYG compared to patients not receiving ART. The lifetime incremental cost is US$2,215 and the undiscounted incremental cost per LYG is US$314. When discounted at 3%, the additional LYG decreases to 5.5 years and the incremental cost per LYG increases to US$325. Conclusion The undiscounted and discounted incremental costs per LYG from introducing ART were less than the per capita GDP threshold at the base year. Thus, ART could be regarded as cost-effective in a district hospital setting in Ethiopia. PMID:19615069

  15. Adherence to highly active antiretroviral therapy impact on clinical and economic outcomes for Medicaid enrollees with HIV and hepatitis C co-infection

    PubMed Central

    Zhang, Shun; Rust, George; Cardarelli, Kathryn; Felizzola, Jesus; Fransua, Mesfin; Stringer, Harold G.

    2016-01-01

    We examined the impact of antiretroviral treatment adherence among Hepatitis C co-infected HIV patients on survival and clinical outcomes. We analyzed Medicaid claims data from fourteen southern states from 2005-2007, comparing survival and clinical outcomes and cost of treatment for HIV and hepatitis-C co-infected patients (N=4,115) at different levels of adherence to antiretroviral therapy.More than one in five patients (20.5%) showed less than 50% adherence to antiretroviral treatment, but there were no racial-ethnic or gender disparities. Significant survival benefit was demonstrated at each incremental level of adherence to antiretroviral therapy (one-year mortality ranging from 3.5% in the highest adherence group to 26.0% in the lowest). Low adherence patients also had higher rates of hospitalization and emergency department visits. Relative to patients with high (>95%) ART-adherence, those with less than 25% treatment adherence had four-fold greater risk of death (adjusted odds ratio 4.22 [95% CI, 3.03,5.87]). Non-drug Medicaid expenditures were lower for high adherence patients, but cost of medications drove total Medicaid expenditures higher for high-adherence patients. Cost per quality-adjusted life year (QALY) saved (relative to the <25% low-adherence group) ranged from $21,874 for increasing adherence to 25-50% to $37,229 for increasing adherence to 75-95%. Adherence to antiretroviral therapy for patients with HIV and hepatitis C co-infection is associated with lower adverse clinical outcomes at a Medicaid cost per QALY commensurate with other well-accepted treatment and prevention strategies. Further research is needed to identify interventions which can best achieve optimal ART adherence at a population scale. PMID:25814041

  16. Chronic Kidney Disease and Antiretroviral Therapy in HIV-Positive Individuals: Recent Developments.

    PubMed

    Achhra, Amit C; Nugent, Melinda; Mocroft, Amanda; Ryom, Lene; Wyatt, Christina M

    2016-06-01

    Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted protease inhibitors (PI/rs), have been associated with increased risk of CKD. However, the CKD risk attributable to these agents is overall small, especially in those with low baseline risk of CKD and normal renal function. CKD risk in HIV-positive individuals can be further minimized by timely identification of those with worsening renal function and discontinuation of potentially nephrotoxic agents. Clinicians can use several monitoring tools, including the D:A:D risk score and routine measurements of estimated glomerular filtration (eGFR) and proteinuria, to identify high-risk individuals who may require an intervention. Tenofovir alafenamide (TAF), a TDF alternative, promises to be safer in terms of TDF-associated kidney and bone toxicity. While the short-term data on TAF does indicate lower eGFR decline and lower risk of proteinuria (vs. TDF), long-term data on renal safety of TAF are still awaited. Promising results have also emerged from recent trials on alternative dual-therapy antiretroviral regimens which exclude the nucleoside(tide) reverse transcriptase class as well as possibly the PI/rs, thereby reducing the drug burden, and possibly the toxicity. However, long-term safety or benefits of these dual-therapy regimens are still unclear and will need to be studied in future prospective studies. Finally, addressing risk factors such as hypertension and diabetes will continue to be important in this population. PMID:27130284

  17. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy

    PubMed Central

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART. PMID:26933317

  18. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    PubMed

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART.

  19. Antiretroviral therapy adherence in persons with HIV/AIDS in Cuba.

    PubMed

    Aragonés, Carlos; Sánchez, Lizet; Campos, Jorge R; Pérez, Jorge

    2011-04-01

    INTRODUCTION Cuba has an HIV prevalence of 0.1% in the population aged 15 to 49 years, very low despite increased incidence in recent years. In 2001, domestically-produced generic antiretroviral therapy was introduced and there has been complete coverage since 2003. In 2006, 1986 people with HIV/AIDS were receiving ART; by 2009, that figure reached 5034. Adherence to antiretroviral therapy is fundamental: nonadherence leads to treatment failure, development of resistance, progression to AIDS, and death. OBJECTIVE Measure levels of treatment adherence and its predictive factors in persons with HIV/AIDS receiving antiretroviral therapy in 2006 in Cuba. METHODS A cross-sectional study was carried out in 2006 of Cuban HIV-positive individuals receiving antiretroviral therapy. A sample size of 876 was calculated using two-stage sampling (first by strata, and then by simple random sampling in each stratum). An anonymous structured questionnaire was administered to participants. Reporting of doses taken on each of the three days and in the week preceding the survey was recoded into five categories. Participants were considered highly adherent if they reported taking ≥95.0% of their medication as prescribed. Reasons for nonadherence were described and logistic regression modeling used to develop hypotheses on associations between high adherence and its predictive factors. RESULTS Interviews were obtained with 847 individuals, 70.6% of whom self reported high adherence. There were no significant differences between highly adherent and less adherent patients with regard to sex, place of residence, treatment setting, time of diagnosis, or length of treatment. Variables associated with high adherence were communication with the specialist physician, change in treatment, memory, self-efficacy, as well as commitment to and opinions about treatment. CONCLUSIONS In Cuba, where treatment is free of charge to patients, adherence is good. Treatment adherence might be improved by

  20. Point of care testing for antiretroviral therapy-related lactic acidosis in resource-poor settings.

    PubMed

    Ivers, Louise C; Mukherjee, Joia S

    2006-03-21

    Lactic acidosis is a rare but potentially life-threatening complication of antiretroviral therapy (ART) and is commonly considered in the differential diagnosis of patients on ART. In the developing world, definitive diagnosis by laboratory measurement of lactate may be impossible. Point-of-care devices are available that provide simple, accurate measurements of lactic acid levels at relatively low cost. Their use in an HIV treatment programme in rural Haiti has greatly assisted clinical decision-making in patients with symptoms suggestive of lactic acidosis. PMID:16514312

  1. Pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in the era of antiretroviral therapy.

    PubMed

    Velásquez, Jorge N; Ledesma, Bibiana A; Nigro, Monica G; Vittar, Natalia; Rueda, Nestor; De Carolis, Luis; Figueiras, Olga; Carnevale, Silvana; Corti, Marcelo

    2016-01-01

    Toxoplasmosis is a severe opportunistic infection in patients infected with the human immunodeficiency virus (HIV). The lung is a major site of infection after the central nervous system. In this report we described two cases of pneumonia due to Toxoplasma gondii infection in HIV patients with antiretroviral therapy. Clinical and radiological abnormalities are not specific. Pulmonary toxoplasmosis should be considered in HIV-infected patients with late stage of HIV, CD4 count less than 100 cells/µl and a poor adherence to HAART. PMID:26933317

  2. A tale of two futures: HIV and antiretroviral therapy in San Francisco.

    PubMed

    Blower, S M; Gershengorn, H B; Grant, R M

    2000-01-28

    The effect of antiretroviral therapy (ART) in preventing human immunodeficiency virus (HIV) infections and averting acquired immunodeficiency syndrome (AIDS) deaths in the San Francisco gay community over the next 10 years was predicted. A transmission model was coupled with a statistical approach that enabled inclusion of a high degree of uncertainty in the potential treatment effects of ART (in terms of infectivity and survival), increase in risky behavior, and rate of emergence of drug resistance. Increasing the usage of ART in San Francisco would decrease the AIDS death rate and could substantially reduce the incidence rate. PMID:10649998

  3. The charms and challenges of antiretroviral therapy in Uganda: the DART experience.

    PubMed

    Nyanzi-Wakholi, Barbara; Lara, Antonieta Medina; Munderi, Paula; Gilks, Charles

    2012-01-01

    Antiretroviral therapy (ART) improves the quality of life of people living with HIV/AIDS. However, adherence remains a challenge. A total of eight focus group discussions (FGD) were conducted with participants from a randomised controlled trial that monitored strategies for managing ART in African adults: Development of Antiretroviral Therapy. All FGD participants had received ART for at least one year. Perceived benefits of ART were key motivators for adherence. These benefits included improved physical health, restored self-esteem, acceptance in the community and hope for a longer and healthier life and reduced fear of HIV/AIDS-related death. Barriers to adherence included a high pill burden, ART side effects and socio-economic constraints, including lack of food and safe water for taking the pills. Visible ART side effects and involvement in an exclusively HIV/AIDS clinic could expose their HIV status, thus exacerbating stigma. Gender and socio-economic differences were found in the variety of strategies employed to ensure adherence. ART was perceived as improving the overall quality of life of recipients; however, it is crucial for ART programmes to be gender and socio-economic cognizant in order to enhance adherence to a lifelong therapy.

  4. Adjunctive and Long-Acting Nanoformulated Antiretroviral Therapies for HIV-associated neurocognitive disorders

    PubMed Central

    Gendelman, Howard E.; Gelbard, Harris A.

    2014-01-01

    Purpose of review This review focuses on current and future strategies to modulate neuroinflammation while reducing residual viral burden in the central nervous system (CNS). This has been realized by targeted long acting antiretroviral nano- and adjunctive therapies being developed for HIV infected people. Our ultimate goal is to eliminate virus from its CNS reservoirs and, in so doing, reverse the cognitive and motor dysfunctions seen in HIV-associated neurocognitive disorders (HAND). Recent findings Herein, we highlight our laboratories development of adjunctive and nanomedicine therapies for HAND. An emphasis is placed on drug-drug interactions that target both the viral life cycle and secretory pro-inflammatory neurotoxic factors and signaling pathways. Summary Antiretroviral therapy (ART) has improved the quality and duration of life for people living with HIV-1. A significant long-term comorbid illness is HAND. Symptoms, while reduced in severity, are common. Disease occurs, in part, through continued low-level viral replication inducing secondary glial neuroinflammatory activities. Our recent works and those of others have seen disease attenuated in animal models through the use of adjunctive and long-acting reservoir targeted nanoformulated ART. The translation of these inventions from animals to humans is the focus of this review. PMID:25226025

  5. Substance abuse, adherence with antiretroviral therapy, and clinical outcomes among HIV-infected individuals

    PubMed Central

    Lucas, Gregory M.

    2010-01-01

    Substance abuse and addiction are highly prevalent in HIV-infected individuals. Substance abuse is an important comorbidity that affects the delivery and outcomes of HIV medical management. In this paper I will review data examining the associations between substance abuse and HIV treatment and potential strategies to improve outcomes in this population that warrant further investigation. Current - but not past - substance abuse adversely affects engagement in care, acceptance of antiretroviral therapy, adherence with therapy, and long-term persistence in care. Substance abuse treatment appears to facilitate engagement in HIV care, and access to evidence-based treatment for substance abuse is central to addressing the HIV epidemic. Strategies that show promise for HIV-infected substance abusers include integrated treatment models, directly observed therapy, and incentive-based interventions. PMID:20888839

  6. Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration

    PubMed Central

    2005-01-01

    Background The genetic differences among HIV-1 subtypes may be critical to clinical management and drug resistance surveillance as antiretroviral treatment is expanded to regions of the world where diverse non-subtype-B viruses predominate. Methods and Findings To assess the impact of HIV-1 subtype and antiretroviral treatment on the distribution of mutations in protease and reverse transcriptase, a binomial response model using subtype and treatment as explanatory variables was used to analyze a large compiled dataset of non-subtype-B HIV-1 sequences. Non-subtype-B sequences from 3,686 persons with well characterized antiretroviral treatment histories were analyzed in comparison to subtype B sequences from 4,769 persons. The non-subtype-B sequences included 461 with subtype A, 1,185 with C, 331 with D, 245 with F, 293 with G, 513 with CRF01_AE, and 618 with CRF02_AG. Each of the 55 known subtype B drug-resistance mutations occurred in at least one non-B isolate, and 44 (80%) of these mutations were significantly associated with antiretroviral treatment in at least one non-B subtype. Conversely, of 67 mutations found to be associated with antiretroviral therapy in at least one non-B subtype, 61 were also associated with antiretroviral therapy in subtype B isolates. Conclusion Global surveillance and genotypic assessment of drug resistance should focus primarily on the known subtype B drug-resistance mutations. PMID:15839752

  7. Pre-Antiretroviral Therapy Serum Selenium Concentrations Predict WHO Stages 3, 4 or Death but not Virologic Failure Post-Antiretroviral Therapy

    PubMed Central

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M.; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R.; Cardoso, Sandra W.; Sugandhavesa, Patcharaphan; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

    2014-01-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28–99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86–95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30–9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

  8. Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.

    PubMed

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

    2014-11-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium. PMID:25401501

  9. Pre-antiretroviral therapy serum selenium concentrations predict WHO stages 3, 4 or death but not virologic failure post-antiretroviral therapy.

    PubMed

    Shivakoti, Rupak; Gupte, Nikhil; Yang, Wei-Teng; Mwelase, Noluthando; Kanyama, Cecilia; Tang, Alice M; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Berendes, Sima; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

    2014-11-01

    A case-cohort study, within a multi-country trial of antiretroviral therapy (ART) efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings (PEARLS)), was conducted to determine if pre-ART serum selenium deficiency is independently associated with human immunodeficiency virus (HIV) disease progression after ART initiation. Cases were HIV-1 infected adults with either clinical failure (incident World Health Organization (WHO) stage 3, 4 or death by 96 weeks) or virologic failure by 24 months. Risk factors for serum selenium deficiency (<85 μg/L) pre-ART and its association with outcomes were examined. Median serum selenium concentration was 82.04 μg/L (Interquartile range (IQR): 57.28-99.89) and serum selenium deficiency was 53%, varying widely by country from 0% to 100%. In multivariable models, risk factors for serum selenium deficiency were country, previous tuberculosis, anemia, and elevated C-reactive protein. Serum selenium deficiency was not associated with either clinical failure or virologic failure in multivariable models. However, relative to people in the third quartile (74.86-95.10 μg/L) of serum selenium, we observed increased hazards (adjusted hazards ratio (HR): 3.50; 95% confidence intervals (CI): 1.30-9.42) of clinical failure but not virologic failure for people in the highest quartile. If future studies confirm this relationship of high serum selenium with increased clinical failure, a cautious approach to selenium supplementation might be needed, especially in HIV-infected populations with sufficient or unknown levels of selenium.

  10. Rates and cost of hospitalisation before and after initiation of antiretroviral therapy in urban and rural settings in South Africa

    PubMed Central

    Meyer-Rath, Gesine; Brennan, Alana T; Fox, Matthew P; Modisenyane, Tebogo; Tshabangu, Nkeko; Mohapi, Lerato; Rosen, Sydney; Martinson, Neil

    2013-01-01

    Few studies have compared hospitalisations before and after antiretroviral therapy (ART) initiation in the same patients. We analysed the cost of hospitalisations among 3,906 adult patients in two South African hospitals, 30% of whom initiated ART. Hospitalisations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count <100 cells/mm3 when compared to 200–350 cells/mm3 in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95% confidence interval, CI, 85–158) for patients on ART and USD 72 (95% CI, 56–89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalisation before and immediately after ART initiation. PMID:23187948

  11. Rates and cost of hospitalization before and after initiation of antiretroviral therapy in urban and rural settings in South Africa.

    PubMed

    Meyer-Rath, Gesine; Brennan, Alana T; Fox, Matthew P; Modisenyane, Tebogo; Tshabangu, Nkeko; Mohapi, Lerato; Rosen, Sydney; Martinson, Neil

    2013-03-01

    Few studies have compared hospitalizations before and after antiretroviral therapy (ART) initiation in the same patients. We analyzed the cost of hospitalizations among 3906 adult patients in 2 South African hospitals, 30% of whom initiated ART. Hospitalizations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count, 100 cells/mm(3) when compared with 200–350 cells/mm(3) in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95%confidence interval, 85 to 158) for patients on ART and USD 72(95% confidence interval, 56 to 89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalization before and immediately after ART initiation. PMID:23187948

  12. Depression During Pregnancy and the Postpartum Among HIV-Infected Women on Antiretroviral Therapy in Uganda

    PubMed Central

    Matthews, Lynn T.; Ashaba, Scholastic; Tsai, Alexander C.; Kanters, Steve; Robak, Magdalena; Psaros, Christina; Kabakyenga, Jerome; Boum, Yap; Haberer, Jessica E.; Martin, Jeffrey N.; Hunt, Peter W.; Bangsberg, David R.

    2014-01-01

    Background: Among HIV-infected women, perinatal depression compromises clinical, maternal, and child health outcomes. Antiretroviral therapy (ART) is associated with lower depression symptom severity but the uniformity of effect through pregnancy and postpartum periods is unknown. Methods: We analyzed prospective data from 447 HIV-infected women (18–49 years) initiating ART in rural Uganda (2005–2012). Participants completed blood work and comprehensive questionnaires quarterly. Pregnancy status was assessed by self-report. Analysis time periods were defined as currently pregnant, postpartum (0–12 months post-pregnancy outcome), or non–pregnancy-related. Depression symptom severity was measured using a modified Hopkins Symptom Checklist 15, with scores ranging from 1 to 4. Probable depression was defined as >1.75. Linear regression with generalized estimating equations was used to compare mean depression scores over the 3 periods. Results: At enrollment, median age was 32 years (interquartile range: 27–37), median CD4 count was 160 cells per cubic millimeter (interquartile range: 95–245), and mean depression score was 1.75 (s = 0.58) (39% with probable depression). Over 4.1 median years of follow-up, 104 women experienced 151 pregnancies. Mean depression scores did not differ across the time periods (P = 0.75). Multivariable models yielded similar findings. Increasing time on ART, viral suppression, better physical health, and “never married” were independently associated with lower mean depression scores. Findings were consistent when assessing probable depression. Conclusions: Although the lack of association between depression and perinatal periods is reassuring, high depression prevalence at treatment initiation and continued incidence across pregnancy and non–pregnancy-related periods of follow-up highlight the critical need for mental health services for HIV-infected women to optimize both maternal and perinatal health. PMID:25436816

  13. Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

    PubMed Central

    Warshaw, Meredith G.; Miller, William C.; Castro, Hannah; Fiscus, Susan A.; Harper, Lynda M.; Harrison, Linda J.; Klein, Nigel J.; Lewis, Joanna; Melvin, Ann J.; Tudor-Williams, Gareth; McKinney, Ross E.

    2014-01-01

    BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation. METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization “mild” immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years. RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with “severe” immunosuppression, more children with “mild” immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or “advanced” immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with “mild” immunosuppression at any age or “advanced” immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%). CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks. PMID:25266426

  14. Short Communication: Persistence of HIV Antibody Avidity in the Presence of Antiretroviral Therapy.

    PubMed

    Curtis, Kelly A; Price, Krystin Ambrose; Niedzwiedz, Philip; Masciotra, Silvina; Owen, Michele

    2016-06-01

    The effects of antiretroviral therapy (ART) on the performance of HIV incidence assays have been well documented. To improve upon current assay approaches or focus the development of future assays, studies are needed to characterize the effects of ART on all candidate HIV incidence assays. In this study, we compared the performance of three antibody avidity-based HIV incidence assays, the Limiting Antigen (LAg), Bio-Rad Avidity, and HIV-1 Multiplex assays, using a well-defined cohort of recent HIV-1 seroconverters composed of ART-naive HIV-1-infected individuals and those who received ART early or delayed in the course of infection. Differences in the performance of all three avidity-based incidence assays were noted with study subjects who received ART. The LAg assay and Multiplex total antibody measurements (nMFI) exhibited similar kinetics in reactivity, as these assays tended to fluctuate with changes in viral load. In the early ART group, all seven subjects remained recent by both assays at time points >1 year postseroconversion, and assay values declined dramatically postdelayed ART initiation. In contrast, the two-well, antibody-dissociation avidity assays, Bio-Rad Avidity and Multiplex avidity index (AI) measurements, continued to mature in the early ART group, although blunted relative to the ART-naive group, and assay values remained stable after delayed ART initiation. In summary, although the HIV incidence assays evaluated in this study are all designed to measure antibody avidity, each assay is affected differently by ART-induced virus suppression, presumably because of the distinct assay formats and procedures for measuring avidity.

  15. Effects of Co-Trimoxazole on Microbial Translocation in HIV-1-Infected Patients Initiating Antiretroviral Therapy.

    PubMed

    Vesterbacka, Jan; Barqasho, Babilonia; Häggblom, Amanda; Nowak, Piotr

    2015-08-01

    Microbial translocation (MT) contributes to immune activation during HIV-1 infection, and persists after initiation of antiretroviral therapy (ART). We investigated whether levels of MT markers are influenced by the use of co-trimoxazole (TMP-SMX) in HIV-1 patients. Plasma samples were obtained from HIV-1-infected patients initiating ART with (n=13) or without (n=13) TMP-SMX prophylaxis. Markers of MT [lipopolysaccharide-binding protein (LBP), lipopolysaccharide (LPS), soluble CD14 (sCD14), and intestinal fatty acid binding protein (I-FABP)] were assessed at baseline (BL), at 1 month, and at 1 year by the Limulus Amebocyte Lysate Assay or ELISA. BL levels of LBP were elevated in both categories of patients; they were highest in patients starting ART and TMP-SMX (median, μg/ml: 36.7 vs. 4.3, respectively, p=0.001) and correlated inversely with CD4(+) T cell counts (ρ=-0.65; p=0.005). Patients receiving ART and TMP-SMX had a significant reduction in LBP between BL and 1 year (median, μg/ml: 36.7 vs. 11.1; p=0.003). In contrast, levels of LPS at BL were lower in patients starting ART and TMP-SMX compared to those without TMP-SMX (median, pg/ml: 221 vs. 303 respectively; p=0.002) and did not change at 1 year. The increased BL levels of sCD14 had declined in both groups at 1 year. No difference in I-FABP levels was found between BL and 1 year. Concomitant use of ART and TMP-SMX reduces microbial translocation markers LBP and sCD14, probably due to its impact on the gut microbiota. Effective ART for 1 year does not restore gut-blood barrier dysfunction. PMID:26059763

  16. Integrated Pre-Antiretroviral Therapy Screening and Treatment for Tuberculosis and Cryptococcal Antigenemia

    PubMed Central

    Pac, Lincoln; Horwitz, Mara; Namutebi, Anne Marion; Auerbach, Brandon J.; Semeere, Aggrey; Namulema, Teddy; Schwarz, Miriam; Bbosa, Robert; Muruta, Allan; Meya, David; Manabe, Yukari C.

    2015-01-01

    Objective To demonstrate the feasibility of integrated screening for cryptococcal antigenemia and tuberculosis (TB) prior to antiretroviral therapy (ART) initiation and to assess disease specific and all-cause mortality in the first 6 months of follow-up. Methods We enrolled a cohort of HIV-infected, ART-naïve adults with CD4 counts ≤ 250 cells/µL in rural Uganda who were followed for 6 months after ART initiation. All subjects underwent screening for TB; those with CD4 ≤ 100 cells/µL also had cryptococcal antigen (CrAg) screening. For those who screened positive, standard treatment for TB or preemptive treatment for cryptococcal infection was initiated, followed by ART two weeks later. Results Of 540 participants enrolled, pre-ART screening detected 10.6% (57/540) with prevalent TB and 6.8% (12/177 with CD4 count ≤ 100 cells/µL) with positive serum CrAg. After ART initiation, 13 (2.4%) patients were diagnosed with TB and one patient developed cryptococcal meningitis. Overall 7.2% of participants died (incidence rate 15.6 per 100 person years at risk). Death rates were significantly higher among subjects with TB and cryptococcal antigenemia compared to subjects without these diagnoses. In multivariate analysis, significant risk factors for mortality were male sex, baseline anemia of hemoglobin ≤ 10 mg/dL, wasting defined as body mass index ≤ 15.5 kg/m2, and opportunistic infections (TB, positive serum CrAg). Conclusion Pre-ART screening for opportunistic infections detects many prevalent cases of TB and cryptococcal infection. However, severely immunosuppressed and symptomatic HIV patients continue to experience high mortality after ART initiation. PMID:25761234

  17. Short Communication: Persistence of HIV Antibody Avidity in the Presence of Antiretroviral Therapy.

    PubMed

    Curtis, Kelly A; Price, Krystin Ambrose; Niedzwiedz, Philip; Masciotra, Silvina; Owen, Michele

    2016-06-01

    The effects of antiretroviral therapy (ART) on the performance of HIV incidence assays have been well documented. To improve upon current assay approaches or focus the development of future assays, studies are needed to characterize the effects of ART on all candidate HIV incidence assays. In this study, we compared the performance of three antibody avidity-based HIV incidence assays, the Limiting Antigen (LAg), Bio-Rad Avidity, and HIV-1 Multiplex assays, using a well-defined cohort of recent HIV-1 seroconverters composed of ART-naive HIV-1-infected individuals and those who received ART early or delayed in the course of infection. Differences in the performance of all three avidity-based incidence assays were noted with study subjects who received ART. The LAg assay and Multiplex total antibody measurements (nMFI) exhibited similar kinetics in reactivity, as these assays tended to fluctuate with changes in viral load. In the early ART group, all seven subjects remained recent by both assays at time points >1 year postseroconversion, and assay values declined dramatically postdelayed ART initiation. In contrast, the two-well, antibody-dissociation avidity assays, Bio-Rad Avidity and Multiplex avidity index (AI) measurements, continued to mature in the early ART group, although blunted relative to the ART-naive group, and assay values remained stable after delayed ART initiation. In summary, although the HIV incidence assays evaluated in this study are all designed to measure antibody avidity, each assay is affected differently by ART-induced virus suppression, presumably because of the distinct assay formats and procedures for measuring avidity. PMID:26887862

  18. Importance of Baseline Prognostic Factors With Increasing Time Since Initiation of Highly Active Antiretroviral Therapy

    PubMed Central

    2012-01-01

    Background The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods We analyzed data on 20,379 treatment-naive HIV-1–infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count <25 cells/µL had persistently higher progression rates than individuals with a baseline CD4 count >350 cells/µL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART. PMID:18043315

  19. Normal Myocardial Flow Reserve in HIV-Infected Patients on Stable Antiretroviral Therapy

    PubMed Central

    Knudsen, Andreas; Christensen, Thomas E.; Ghotbi, Adam Ali; Hasbak, Philip; Lebech, Anne-Mette; Kjær, Andreas; Ripa, Rasmus Sejersten

    2015-01-01

    Abstract Studies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population. In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ≤1.5, borderline >1.5 to 2.0, or normal >2.0. Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37–68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36–68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress. PMID:26512605

  20. Drug-Resistant Tuberculosis among HIV-Infected Patients Starting Antiretroviral Therapy in Durban, South Africa

    PubMed Central

    Hom, Jeffrey K.; Wang, Bingxia; Chetty, Senica; Giddy, Janet; Mazibuko, Matilda; Allen, Jenny; Walensky, Rochelle P.; Losina, Elena; Freedberg, Kenneth A.; Bassett, Ingrid V.

    2012-01-01

    Objective To estimate the prevalence of drug-resistant tuberculosis (TB) and describe the resistance patterns in patients commencing antiretroviral therapy (ART) in an HIV clinic in Durban, South Africa. Design Cross-sectional cohort study. Methods Consecutive HIV-infected adults (≥18y/o) initiating HIV care were enrolled from May 2007–May 2008, regardless of signs or symptoms of active TB. Prior TB history and current TB treatment status were self-reported. Subjects expectorated sputum for culture (MGIT liquid and 7H11 solid medium). Positive cultures were tested for susceptibility to first- and second-line anti-tuberculous drugs. The prevalence of drug-resistant TB, stratified by prior TB history and current TB treatment status, was assessed. Results 1,035 subjects had complete culture results. Median CD4 count was 92/µl (IQR 42–150/µl). 267 subjects (26%) reported a prior history of TB and 210 (20%) were receiving TB treatment at enrollment; 191 (18%) subjects had positive sputum cultures, among whom the estimated prevalence of resistance to any antituberculous drug was 7.4% (95% CI 4.0–12.4). Among those with prior TB, the prevalence of resistance was 15.4% (95% CI 5.9–30.5) compared to 5.2% (95% CI 2.1–8.9) among those with no prior TB. 5.1% (95% CI 2.4–9.5) had rifampin or rifampin plus INH resistance. Conclusions The prevalence of TB resistance to at least one drug was 7.4% among adults with positive TB cultures initiating ART in Durban, South Africa, with 5.1% having rifampin or rifampin plus INH resistance. Improved tools for diagnosing TB and drug resistance are urgently needed in areas of high HIV/TB prevalence. PMID:22912845

  1. Antiretroviral therapy adherence strategies used by patients of a large HIV clinic in Lesotho.

    PubMed

    Axelsson, Johanna Maria; Hallager, Sofie; Barfod, Toke S

    2015-01-01

    A high degree of adherence to antiretroviral therapy (ART) in patients infected with human immunodeficiency virus (HIV) is necessary for long term treatment effects. This study explores the role of timing of ART intake, the information patients received from health workers, local adherence patterns, barriers to and facilitators of ART among 28 HIV-positive adults at the Senkatana HIV Clinic in Maseru, Lesotho. This qualitative, semi-structured interview study was carried out during February and March of 2011 and responses were analyzed inspired by the Grounded Theory method. Results were then compared and discussed between the authors and the main themes that emerged were categorized. The majority of the respondents reported having missed one or more doses of medicine in the past and it was a widespread belief among patients that they were required to skip the dose of ART if they were "late". The main barriers to adherence were interruptions of daily routines or leaving the house without sufficient medicine. The use of mobile phone alarms, phone clocks and support from family and friends were major facilitators of adherence. None of the patients reported to have been counseled on family support or the use of mobile phones as helpful methods in maintaining or improving adherence to ART. Being on-time with ART was emphasized during counseling by health workers. In conclusion, patients should be advised to take the dose as soon as they remember instead of skipping the dose completely when they are late. Mobile phones and family support could be subjects to focus on during future counseling particularly with the growing numbers of mobile phones in Africa and the current focus on telemedicine. PMID:26825572

  2. Effect of Different Types of Exercise in HIV + Mozambican Women Using Antiretroviral Therapy

    PubMed Central

    Mangona, Lucília; Daca, Timóteo; Tchonga, Francisco; Bule, Odete; Bhatt, Nilesh; Jani, Ilesh; Damasceno, Albertino; Prista, António

    2015-01-01

    The aim of this study was to evaluate and compare the effect of two types of exercises interventions on the regularity and health-related physical fitness in HIV-infected individuals who use antiretroviral therapy (ART). A total of 53 HIV+ African women (mean age=39.5±8.4 years) on ART participated in the study. Subjects were randomly divided into 3 groups, namely, formal exercise (FEG), playful exercise (PEG) and control (CG). During 12 weeks, the exercise groups underwent a program of 1-hour duration with a frequency of 3 times a week. The FEG performed a protocol that included 20 minutes of exercise, cycling at 60 % of V̇O2peak, increasing to 75 % and 85 % in the 4th and 8th weeks, respectively, and a muscular endurance circuit consisted of 6 exercises at 15 repetitions per minute (RM). The PEG followed a program consisting of active games. Before and after the intervention the participants were submitted to a clinical evaluation including immunological parameters (CD4+), cardiovascular risk factors, physical fitness and anthropometry. Comparison of somatic variables before and after the program showed no exercise effect. Immunological and cardiovascular variables were also independent of the exercise group. The main effect was found in cardiorespiratory fitness: exercise groups increased significantly in V̇O2peak (FEG=14.7 %; PEG=11.1 %) with no significant differences in CG. The percentage of high attendance was identical between the two groups. It was concluded that there is no contraindication for exercise in this type of population and the beneficial effect was mainly in cardiorespiratory fitness, regardless of the type of exercise performed. PMID:26587077

  3. Effectiveness of Hormonal Contraception in HIV-Infected Women using Antiretroviral Therapy: A Prospective Study

    PubMed Central

    Pyra, Maria; Heffron, Renee; Mugo, Nelly R.; Nanda, Kavita; Thomas, Katherine K.; Celum, Connie; Kourtis, Athena P.; Were, Edwin; Rees, Helen; Bukusi, Elizabeth; Baeten, Jared M.

    2015-01-01

    Objective To assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. Methods Using data from 5,153 HIV-infected women followed prospectively one to three years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral, or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHR) and test interactions between each method and ART use. Results During follow-up, 9% of women ever used implants, 40% used injectables, and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART (aHR 0.06, 95% CI 0.01-0.45) and not on ART (aHR 0.05, 95% CI 0.02-0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed non-statistically significant reduced effectiveness when concurrently using efavirenz. Conclusion Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use. PMID:26544706

  4. Cholelithiasis and Nephrolithiasis in HIV-Positive Patients in the Era of Combination Antiretroviral Therapy

    PubMed Central

    Lin, Kuan-Yin; Liao, Sih-Han; Liu, Wen-Chun; Cheng, Aristine; Lin, Shu-Wen; Chang, Sui-Yuan; Tsai, Mao-Song; Kuo, Ching-Hua; Wu, Mon-Ro; Wang, Hsiu-Po; Hung, Chien-Ching; Chang, Shan-Chwen

    2015-01-01

    Objectives This study aimed to describe the epidemiology and risk factors of cholelithiasis and nephrolithiasis among HIV-positive patients in the era of combination antiretroviral therapy. Methods We retrospectively reviewed the medical records of HIV-positive patients who underwent routine abdominal sonography for chronic viral hepatitis, fatty liver, or elevated aminotransferases between January 2004 and January 2015. Therapeutic drug monitoring of plasma concentrations of atazanavir was performed and genetic polymorphisms, including UDP-glucuronosyltransferase (UGT) 1A1*28 and multidrug resistance gene 1 (MDR1) G2677T/A, were determined in a subgroup of patients who received ritonavir-boosted or unboosted atazanavir-containing combination antiretroviral therapy. Information on demographics, clinical characteristics, and laboratory testing were collected and analyzed. Results During the 11-year study period, 910 patients who underwent routine abdominal sonography were included for analysis. The patients were mostly male (96.9%) with a mean age of 42.2 years and mean body-mass index of 22.9 kg/m2 and 85.8% being on antiretroviral therapy. The anchor antiretroviral agents included non-nucleoside reverse-transcriptase inhibitors (49.3%), unboosted atazanavir (34.4%), ritonavir-boosted lopinavir (20.4%), and ritonavir-boosted atazanavir (5.5%). The overall prevalence of cholelithiasis and nephrolithiasis was 12.5% and 8.2%, respectively. Among 680 antiretroviral-experienced patients with both baseline and follow-up sonography, the crude incidence of cholelithiasis and nephrolithiasis was 4.3% and 3.7%, respectively. In multivariate analysis, the independent factors associated with incident cholelithiasis were exposure to ritonavir-boosted atazanavir for >2 years (adjusted odds ratio [AOR], 6.29; 95% confidence interval [CI], 1.12–35.16) and older age (AOR, 1.04; 95% CI, 1.00–1.09). The positive association between duration of exposure to ritonavir

  5. Early antiretroviral therapy: rationale, protease inhibitor-sparing regimens and once daily dosing.

    PubMed

    Gatell, J M

    1998-01-01

    In 1998 it seems reasonable and widely accepted that all human immunodeficiency virus type 1 (HIV-1)-infected patients willing to be treated may benefit from receiving antiretroviral therapy. Only those with undetectable plasma HIV-1 RNA, normal CD4 lymphocyte counts and lack of markers of immunological system activation may be possible exceptions. The rationale supporting the early initiation of antiretroviral therapy are (i) data on viral dynamics; (ii) preliminary data pointing toward a better and a quicker restoration of immune function when treatment is initiated in very early stages (during or within a few weeks or months of acute symptomatic or asymptomatic HIV-1 infection); (iii) the lack of a stable viral load set-point even in patients in the early stages (CD4 > 500 cells/mm3) who have a very low viral load (< 5000 copies/ml); (iv) the relatively high likelihood of clinical progression at mid-term of the approximately 50-75% of patients in very early disease stages (CD4 > 500 cells/mm3) who have a plasma viral load above 5000 to 10,000 HIV-1 RNA copies/ml; (v) data from the Spanish Earth-1 study, which used a composite endpoint (virological, immunological or clinical progression), demonstrating that even in these very early stages of HIV-1 disease any antiretroviral therapy (double or triple combination) was better than no treatment. Even in early disease stages, a triple combination is needed to achieve a durable and profound virological and immunological response. In addition, the combination of stavudine plus didanosine has several advantages and can be considered one of the best double nucleoside combinations to combine with a protease inhibitor or with a non-nucleoside reverse transcriptase inhibitor. The INCAS study and the preliminary results of the ongoing Spanish SCAN study have demonstrated the possibility of protease inhibitor-sparing combinations for initial antiretroviral treatment, at least in selected patient subsets, such as those with a

  6. Patient- and population-level health consequences of discontinuing antiretroviral therapy in settings with inadequate HIV treatment availability

    PubMed Central

    2012-01-01

    Background In resource-limited settings, HIV budgets are flattening or decreasing. A policy of discontinuing antiretroviral therapy (ART) after HIV treatment failure was modeled to highlight trade-offs among competing policy goals of optimizing individual and population health outcomes. Methods In settings with two available ART regimens, we assessed two strategies: (1) continue ART after second-line failure (Status Quo) and (2) discontinue ART after second-line failure (Alternative). A computer model simulated outcomes for a single cohort of newly detected, HIV-infected individuals. Projections were fed into a population-level model allowing multiple cohorts to compete for ART with constraints on treatment capacity. In the Alternative strategy, discontinuation of second-line ART occurred upon detection of antiretroviral failure, specified by WHO guidelines. Those discontinuing failed ART experienced an increased risk of AIDS-related mortality compared to those continuing ART. Results At the population level, the Alternative strategy increased the mean number initiating ART annually by 1,100 individuals (+18.7%) to 6,980 compared to the Status Quo. More individuals initiating ART under the Alternative strategy increased total life-years by 15,000 (+2.8%) to 555,000, compared to the Status Quo. Although more individuals received treatment under the Alternative strategy, life expectancy for those treated decreased by 0.7 years (−8.0%) to 8.1 years compared to the Status Quo. In a cohort of treated patients only, 600 more individuals (+27.1%) died by 5 years under the Alternative strategy compared to the Status Quo. Results were sensitive to the timing of detection of ART failure, number of ART regimens, and treatment capacity. Although we believe the results robust in the short-term, this analysis reflects settings where HIV case detection occurs late in the disease course and treatment capacity and the incidence of newly detected patients are stable. Conclusions

  7. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  8. Effect of a Smartphone Application Incorporating Personalized Health-Related Imagery on Adherence to Antiretroviral Therapy: A Randomized Clinical Trial

    PubMed Central

    Perera, Anna I.; Thomas, Mark G.; Moore, John O.; Faasse, Kate

    2014-01-01

    Abstract Poor adherence to combination antiretroviral therapy (ART) is a major global challenge. In this study we examined the efficacy of a smartphone application incorporating personalized health-related visual imagery that provided real-time information about the level of medication and the patient's level of immunoprotection, in order to improve adherence to ART. We randomized 28 people on ART to either a standard or augmented version of the smartphone application. The augmented version contained components that illustrated participants' current estimated plasma concentrations of antiretroviral drugs and the immune protection provided by ART. Adherence to ART was assessed at baseline and at 3 months using self-reported adherence, pharmacy dispensing records, and HIV viral load. Information was also collected on illness and medication beliefs and use of the application. Participants who received the augmented application showed a significantly higher level of self-reported adherence to ART at 3 months (p=0.03) and decreased viral load (p=0.023) as compared to individuals using the standard version. Greater usage of the extra components of the augmented application was associated with greater perceived understanding of HIV infection and increased perceived necessity for ART. Smartphone applications that incorporate personalized health-related visual imagery may have potential to improve adherence to ART. PMID:25290556

  9. Treatment outcomes in a decentralized antiretroviral therapy program: a comparison of two levels of care in north central Nigeria.

    PubMed

    Okonkwo, Prosper; Sagay, Atiene S; Agaba, Patricia A; Yohanna, Stephen; Agbaji, Oche O; Imade, Godwin E; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A; Idoko, John A; Kanki, Phyllis J

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care.

  10. Antiretroviral therapy for prevention of HIV transmission in HIV-discordant couples

    PubMed Central

    Anglemyer, Andrew; Rutherford, George W; Horvath, Tara; Baggaley, Rachel C; Egger, Matthias; Siegfried, Nandi

    2014-01-01

    Background Antiretroviral drugs have been shown to reduce risk of mother-to-child transmission of human immunodeficiency virus (HIV) and are also widely used for post-exposure prophylaxis for parenteral and sexual exposures. Sexual transmission may be lower in couples in which one partner is infected with HIV and the other is not and the infected partner is on antiretroviral therapy (ART). Objectives To determine if ART use in an HIV-infected member of an HIV-discordant couple is associated with lower risk of HIV transmission to the uninfected partner compared to untreated discordant couples. Search methods We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language. Selection criteria Randomised controlled trials (RCT), cohort studies and case-control studies of HIV-discordant couples in which the HIV-infected member of the couple was being treated or not treated with ART Data collection and analysis Abstracts of all trials identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 3,833 references and examined 87 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form. Main results One RCT and nine observational studies were included in the review. These ten studies identified 2,112 episodes of HIV transmission, 1,016 among treated couples and 1,096 among untreated couples. The rate ratio for the single randomised controlled trial was 0.04 [95% CI 0.00, 0.27]. All index partners in this study had CD4 cell counts at baseline of 350–550 cells/µL. Similarly, the summary rate ratio for the nine observational studies was 0.58 [95% CI 0.35, 0.96], with substantial heterogeneity (I2=64%). After excluding two studies with inadequate person-time data, we estimated a summary rate ratio of 0.36 [95%CI 0.17, 0.75] with substantial heterogeneity (I2=62%). We also performed

  11. Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy

    PubMed Central

    Sadiq, Shamiya; Khajuria, Vijay; Mahajan, Annil; Singh, Jang B.

    2015-01-01

    Background and Objectives Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). Materials and Methods A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. Results Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. Conclusion The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field. PMID:26557538

  12. Critical Review: What Dose of Rifabutin Is Recommended With Antiretroviral Therapy?

    PubMed

    Yapa, H Manisha; Boffito, Marta; Pozniak, Anton

    2016-06-01

    Since the advent of combination antiretroviral therapy to successfully treat HIV infection, drug-drug interactions (DDIs) have become a significant problem as many antiretrovirals (ARVs) are metabolized in the liver. Antituberculous therapy traditionally includes rifamycins, particularly rifampicin. Rifabutin (RBT) has shown similar efficacy as rifampicin but induces CYP3A4 to a lesser degree and is less likely to have DDIs with ARVs. We identified 14 DDI pharmacokinetic studies on HIV monoinfected and HIV-tuberculosis coinfected individuals, and the remaining studies were healthy volunteer studies. Although RBT may be coadministered with most nonnucleoside reverse transcriptase inhibitors, identifying the optimal dose with ritonavir-boosted or cobicistat-boosted protease inhibitors is challenging because of concern about adverse effects with increased RBT exposure. Limited healthy volunteer studies on other ARV drug classes and RBT suggest that dose modification may be unnecessary. The paucity of data assessing clinical tuberculosis endpoints concurrently with RBT and ARV pharmacokinetics limits evidence-based recommendations on the optimal dose of RBT within available ARV drug classes. PMID:26855245

  13. Influence of the First Consultation on Adherence to Antiretroviral Therapy for HIV-infected Patients

    PubMed Central

    Peyre, Marion; Gauchet, Aurélie; Roustit, Matthieu; Leclercq, Pascale; Epaulard, Olivier

    2016-01-01

    Background: Physician attitude influences the way patients cope with diagnosis and therapy in chronic severe diseases such as cancer. Previous studies showed that such an effect exists in HIV care; it is likely that it begins with the first contact with a physician. Objective: We aimed to explore in HIV-infected persons their perception of the first consultation they had with an HIV specialist (PFC-H), and whether this perception correlates with adherence to antiretroviral therapy. Method: The study was conducted in Grenoble University Hospital, France, a tertiary care center. Every antiretroviral-experienced patient was asked to freely complete a self-reported, anonymous questionnaire concerning retrospective PFC-H, present adherence (Morisky scale), and present perceptions and beliefs about medicine (BMQ scale). Results: One hundred and fifty-one questionnaires were available for evaluation. PFC-H score and adherence were correlated, independently from age, gender, and numbers of pill(s) and of pill intake(s) per day. BMQ score also correlated with adherence; structural equation analysis suggested that the effect of PFC-H on adherence is mediated by positive beliefs. Conclusion: These results suggest that for HIV-infected persons, the perceptions remaining from the first consultation with an HIV specialist physician influence important issues such as adherence and perception about medicine. Physicians must be aware of this potentially long-lasting effect. PMID:27708747

  14. Decline in HIV infectivity following the introduction of highly active antiretroviral therapy

    PubMed Central

    Porco, Travis C.; Martin, Jeffrey N.; Page-Shafer, Kimberly A.; Cheng, Amber; Charlebois, Edwin; Grant, Robert M.; Osmond, Dennis H.

    2008-01-01

    Objective Little is known about the degree to which widespread use of antiretroviral therapy in a community reduces uninfected individuals’ risk of acquiring HIV. We estimated the degree to which the probability of HIV infection from an infected partner (the infectivity) declined following the introduction of highly active antiretroviral therapy (HAART) in San Francisco. Design Homosexual men from the San Francisco Young Men’s Health Study, who were initially uninfected with HIV, were asked about sexual practices, and tested for HIV antibodies at each of four follow-up visits during a 6-year period spanning the advent of widespread use of HAART (1994 to 1999). Methods We estimated the infectivity of HIV (per-partnership probability of transmission from an infected partner) using a probabilistic risk model based on observed incident infections and self-reported sexual risk behavior, and tested the hypothesis that infectivity was the same before and after HAART was introduced. Results A total of 534 homosexual men were evaluated. Decreasing trends in HIV seroincidence were observed despite increases in reported number of unprotected receptive anal intercourse partners. Conservatively assuming a constant prevalence of HIV infection between 1994 and 1999, HIV infectivity decreased from 0.120 prior to widespread use of HAART, to 0.048 after the widespread use of HAART – a decline of 60% (P = 0.028). Conclusions Use of HAART by infected persons in a community appears to reduce their infectiousness and therefore may provide an important HIV prevention tool. PMID:15090833

  15. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a man with AIDS.

    PubMed

    Yoganathan, Katie; Brown, David; Yoganathan, Kathir

    2012-01-01

    A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML). His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm(3). Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report. PMID:22536089

  16. [Clinical and immunological profile of HIV-infected patients at the initiation of antiretroviral therapy in Douala].

    PubMed

    Essomba, N E; Mbatchou Ngahane, B H; Nida, M; Temfack, E; Mapoure Njankouo, Y; Abeng, R L; Fokalbo, Z Kobe; Achu Joko, H; Mbenoun, M; Meledie, A P; Halle, M P; Malongue, A; Tchente, C; Nana Njamen, T; Halle Ekane, G; Ngwane, S; Barla, E; Abena, P; Ndobo, P; Moungo Kuidjeu, C; Adiogo, D; Mouelle Sone, A; Luma Namme, H; Coppieters, Y

    2015-10-01

    The aim of this study was to describe the clinical and immunological profile of patients infected with HIV after initiation of antiretroviral therapy. Sociodemographic characteristics, clinical and immunological patients were recorded. Chi square test and Mann-Whitney were used to compare variables. The multivariate regression model identified risk factors. So that, 936 (56.2%) patients were in stages III and IV of the WHO and 65.2% at an advanced stage of the disease. Factors associated with initiation at an advanced stage, were male sex (p = 0.007) and time to diagnosis (p = 0.005). In 2/3 cases, treatment is started at an advanced stage of disease. It is therefore important to intensify awareness campaigns for early detection and encourage patients to ensure regular medical follow-up screening. PMID:26296430

  17. Antiretroviral effect of lovastatin on HIV-1-infected individuals without highly active antiretroviral therapy (The LIVE study): a phase-II randomized clinical trial

    PubMed Central

    Montoya, Carlos J; Jaimes, Fabian; Higuita, Edwin A; Convers-Páez, Sandra; Estrada, Santiago; Gutierrez, Francisco; Amariles, Pedro; Giraldo, Newar; Peñaloza, Cristina; Rugeles, Maria T

    2009-01-01

    Background Highly active antiretroviral therapy produces a significant decrease in HIV-1 replication and allows an increase in the CD4 T-cell count, leading to a decrease in the incidence of opportunistic infections and mortality. However, the cost, side effects and complexity of antiretroviral regimens have underscored the immediate need for additional therapeutic approaches. Statins exert pleiotropic effects through a variety of mechanisms, among which there are several immunoregulatory effects, related and unrelated to their cholesterol-lowering activity that can be useful to control HIV-1 infection. Methods/design Randomized, double-blinded, placebo controlled, single-center, phase-II clinical trial. One hundred and ten chronically HIV-1-infected patients, older than 18 years and naïve for antirretroviral therapy (i.e., without prior or current management with antiretroviral drugs) will be enrolled at the outpatient services from the most important centres for health insurance care in Medellin-Colombia. The interventions will be lovastatin (40 mg/day, orally, for 12 months; 55 patients) or placebo (55 patients). Our primary aim will be to determine the effect of lovastatin on viral replication. The secondary aim will be to determine the effect of lovastatin on CD4+ T-cell count in peripheral blood. As tertiary aims we will explore differences in CD8+ T-cell count, expression of activation markers (CD38 and HLA-DR) on CD4 and CD8 T cells, cholesterol metabolism, LFA-1/ICAM-1 function, Rho GTPases function and clinical evolution between treated and not treated HIV-1-infected individuals. Discussion Preliminary descriptive studies have suggested that statins (lovastatin) may have anti HIV-1 activity and that their administration is safe, with the potential effect of controlling HIV-1 replication in chronically infected individuals who had not received antiretroviral medications. Considering that there is limited clinical data available on this topic, all these

  18. 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

  19. Social, Cultural, and Environmental Challenges Faced by Children on Antiretroviral Therapy in Zimbabwe: a Mixed-Method Study

    PubMed Central

    Macherera, Margaret; Moyo, Lindani; Ncube, Mkhanyiseli; Gumbi, Angella

    2012-01-01

    Objectives Despite the advent of antiretroviral therapy (ART), many children, particularly in the rural communities of Zimbabwe, remain vulnerable. The purpose of this study was to determine the factors and challenges facing children on antiretroviral therapy (ART) in Brunapeg area of Mangwe District, Zimbabwe. Methods A mixed-method approach involving interviewer-guided focus group discussions and piloted semi-structured questionnaires was utilized to collect data from different key population groups. The data obtained were analyzed through content coding procedures based on a set of predetermined themes of interest. Results A number of challenges emerged as barriers to the success of antiretroviral therapy for children. Primary care givers were less informed about HIV and AIDS issues for people having direct impact on the success of antiretroviral therapy in children whilst some were found to be taking the antiretroviral drugs meant for the children. It also emerged that some primary care givers were either too young or too old to care for the children while others had failed to disclose to the children why they frequently visited the Opportunistic Infections (OI) clinic. Most primary care givers were not the biological parents of the affected children. Other challenges included inadequate access to health services, inadequate food and nutrition and lack of access to clean water, good hygiene and sanitation. The lack of community support and stigma and discrimination affected their school attendance and hospital visits. All these factors contributed to non-adherence to antiretroviral drugs. Conclusions and Public Health Implications Children on ART in rural communities in Zimbabwe remain severely compromised and have unique problems that need multi-intervention strategies both at policy and programmatic levels. Effective mitigating measures must be fully established and implemented in rural communities of developing countries in the fight for universal

  20. Factors influencing medication adherence beliefs and self-efficacy in persons naive to antiretroviral therapy: a multicenter, cross-sectional study.

    PubMed

    Reynolds, Nancy R; Testa, Marcia A; Marc, Linda G; Chesney, Margaret A; Neidig, Judith L; Smith, Scott R; Vella, Stefano; Robbins, Gregory K

    2004-06-01

    It is widely recognized that adherence to antiretroviral therapy is critical to long-term treatment success, yet rates of adherence to antiretroviral medications are frequently subtherapeutic. Beliefs about antiretroviral therapy and psychosocial characteristics of HIV-positive persons naive to therapy may influence early experience with antiretroviral medication adherence and therefore could be important when designing programs to improve adherence to antiretroviral therapy. As part of a multicenter AIDS Clinical Trial Group (ACTG 384) study, 980 antiretroviral-naive subjects (82% male, 47% White, median age 36 years, and median CD4 cell count 278 cells/mm3) completed a self-administered questionnaire prior to random treatment assignment of initial antiretroviral medications. Measures of symptom distress, general health and well-being, and personal and situational factors including demographic characteristics, social support, self-efficacy, depression, stress, and current adherence to (nonantiretroviral) medications were recorded. Associations among variables were explored using correlation and regression analyses. Beliefs about the importance of antiretroviral adherence and ability to take antiretroviral medications as directed (adherence self-efficacy) were generally positive. Fifty-six percent of the participants were "extremely sure" of their ability to take all medications as directed and 48% were "extremely sure" that antiretroviral nonadherence would cause resistance, but only 37% were as sure that antiretroviral therapy would benefit their health. Less-positive beliefs about antiretroviral therapy adherence were associated with greater stress, depression, and symptom distress. More-positive beliefs about antiretroviral therapy adherence were associated with better scores on health perception, functional health, social-emotional-cognitive function, social support, role function, younger age, and higher education (r values = 0.09-0.24, all p < .001). Among

  1. 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

  2. Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

    PubMed Central

    Labhardt, Niklaus Daniel; Keiser, Olivia; Sello, Motlalepula; Lejone, Thabo Ishmael; Pfeiffer, Karolin; Davies, Mary-Ann; Egger, Matthias; Ehmer, Jochen; Wandeler, Gilles

    2013-01-01

    Introduction Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73–1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20–1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51–0.93). Conclusions In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to

  3. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

    PubMed Central

    Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

    2001-01-01

    In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

  4. Antiretroviral Resistance After First-Line Antiretroviral Therapy Failure in Diverse HIV-1 Subtypes in the SECOND-LINE Study.

    PubMed

    Lam, Edward P; Moore, Cecilia L; Gotuzzo, Eduardo; Nwizu, Chidi; Kamarulzaman, Adeeba; Chetchotisakd, Ploenchan; van Wyk, Jean; Teppler, Hedy; Kumarasamy, Nagalingeswaran; Molina, Jean-Michel; Emery, Sean; Cooper, David A; Boyd, Mark A

    2016-09-01

    We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p < .2. The exclusion p-value from stepwise elimination was p > .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p < .001). Subtype CRF01_AE was associated with ≥3 N(t)RTI mutations (OR = 2.34; 95% CI 1.31-4.17; p = .004) and higher RPV resistance (OR = 2.13; 95% CI 1.30-3.49; p = .003), and subtype C was associated with <3 TAMs (OR = 0.45; 95% CI 0.21-0.99; p = .015). Subtypes CRF01_AE (OR = 2.46; 95% CI 1.26-4.78; p = .008) and G (OR = 4.77; 95% CI 1.44-15.76; p = .01) were associated with K65/K70 mutations. Higher VL at confirmed first-line VF was

  5. Adherence to antiretroviral therapy and its determinants among persons living with HIV/AIDS in Bayelsa state, Nigeria

    PubMed Central

    Suleiman, Ismail A.; Momo, Andrew

    2015-01-01

    Background: A high level of adherence is required to achieve the desired outcomes of antiretroviral therapy. There is paucity of information about adherence to combined antiretroviral therapy in Bayelsa State of southern Nigeria. Objectives: The objectives of the study were to determine the level of adherence to combined antiretroviral therapy among the patients, evaluate the improvement in their immune status and identify reasons for sub-optimal adherence to therapy. Methods: The cross-sectional study involved administration of an adapted and pretested questionnaire to 601 consented patients attending the two tertiary health institutions in Bayesla State, Nigeria: The Federal Medical Centre, Yenagoa and the Niger-Delta University Teaching Hospital Okolobiri. The tool was divided into various sections such as socio-demographic data, HIV knowledge and adherence to combined antiretroviral therapy. Information on the patient’s CD4+ T cells count was retrieved from their medical records. Adherence was assessed by asking patients to recall their intake of prescribed doses in the last fourteen days and subjects who had 95-100% of the prescribed antiretroviral drugs were considered adherent. Results: Three hundred and forty eight (57.9%) of the subjects were females and 253 (42.1%) were males. The majority of them, 557 (92.7%) have good knowledge of HIV and combined anti-retroviral therapy with a score of 70.0% and above. A larger proportion of the respondents, 441 (73.4%), had ≥95% adherence. Some of the most important reasons giving for missing doses include, “simply forgot” 147 (24.5%), and “wanted to avoid the side-effects of drugs” 33(5.5%). There were remarkable improvements in the immune status of the subjects with an increment in the proportion of the subjects with CD4+ T cells count of greater than 350 cells/mm3 from 33 (5.5%) at therapy initiation to 338 (56.3%) at study period (p<0.0001). Conclusion: The adherence level of 73.4% was low which calls

  6. Estimating age-based antiretroviral therapy costs for HIV-infected children in resource-limited settings based on World Health Organization weight-based dosing recommendations

    PubMed Central

    2014-01-01

    Background Pediatric antiretroviral therapy (ART) has been shown to substantially reduce morbidity and mortality in HIV-infected infants and children. To accurately project program costs, analysts need accurate estimations of antiretroviral drug (ARV) costs for children. However, the costing of pediatric antiretroviral therapy is complicated by weight-based dosing recommendations which change as children grow. Methods We developed a step-by-step methodology for estimating the cost of pediatric ARV regimens for children ages 0–13 years old. The costing approach incorporates weight-based dosing recommendations to provide estimated ARV doses throughout childhood development. Published unit drug costs are then used to calculate average monthly drug costs. We compared our derived monthly ARV costs to published estimates to assess the accuracy of our methodology. Results The estimates of monthly ARV costs are provided for six commonly used first-line pediatric ARV regimens, considering three possible care scenarios. The costs derived in our analysis for children were fairly comparable to or slightly higher than available published ARV drug or regimen estimates. Conclusions The methodology described here can be used to provide an accurate estimation of pediatric ARV regimen costs for cost-effectiveness analysts to project the optimum packages of care for HIV-infected children, as well as for program administrators and budget analysts who wish to assess the feasibility of increasing pediatric ART availability in constrained budget environments. PMID:24885453

  7. Highly active antiretroviral therapy and tuberculosis control in Africa: synergies and potential.

    PubMed Central

    Harries, Anthony D.; Hargreaves, Nicola J.; Chimzizi, Rehab; Salaniponi, Felix M.

    2002-01-01

    HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and TB (tuberculosis) are two of the world's major pandemics, the brunt of which falls on sub-Saharan Africa. Efforts aimed at controlling HIV/AIDS have largely focused on prevention, little attention having been paid to care. Work on TB control has concentrated on case detection and treatment. HIV infection has complicated the control of tuberculosis. There is unlikely to be a decline in the number of cases of TB unless additional strategies are developed to control both this disease and HIV simultaneously. Such strategies would include active case-finding in situations where TB transmission is high, the provision of a package of care for HIV-related illness, and the application of highly active antiretroviral therapy. The latter is likely to have the greatest impact, but for this therapy to become more accessible in Africa the drugs would have to be made available through international support and a programme structure would have to be developed for its administration. It could be delivered by means of a structure based on the five-point strategy called DOTS, which has been adopted for TB control. However, it may be unrealistic to give TB control programmes the responsibility for running such a programme. A better approach might be to deliver highly active antiretroviral therapy within a comprehensive HIV/AIDS management strategy complementing the preventive work already being undertaken by AIDS control programmes. TB programmes could contribute towards the development and implementation of this strategy. PMID:12132003

  8. Antiretroviral Therapy and Health Care Utilization: A Study of Privately Insured Men and Women with HIV Disease

    PubMed Central

    Hellinger, Fred J; Encinosa, William E

    2004-01-01

    Objective To compare the use of antiretroviral therapy and other health care resources by women and men with HIV disease who are privately insured. Data Sources Data were obtained from the MarketScan Commercial Claims and Encounter Database produced by the Medstat Group, Inc., of Ann Arbor, Michigan. This database includes eligibility files as well as claims data for inpatient care, outpatient care, physician services, and prescription drugs for enrollees in employer-sponsored benefit plans for 24 large employers around the nation. Study Design Examine utilization by 2,026 privately insured persons (1,494 men and 532 women) with HIV disease in calendar year 2000 under the age of 65. Principal Findings Using a simple comparison, we found that 71 percent of men (68.7 to 73.3 percent is 95 percent confidence interval) and 39 percent of women (35.1 to 43.5 percent is 95 percent confidence interval) with HIV disease received antiretroviral therapy. We also found that the average annual drug cost was $9,037 for a man ($8,372 to $9,702 is 95 percent confidence interval) and $3,893 for a woman ($3,476 to $4,490 is 95 percent confidence interval). Furthermore, we found that the out-of-pocket expenses comprised 10 percent of total expenses for men ($1,617 out of $16,405) and 4 percent for women ($405 out of $10,397). Conclusion There are major differences in the utilization and cost of health care between privately insured men and women with HIV disease. PMID:15230936

  9. Compulsory licensing often did not produce lower prices for antiretrovirals compared to international procurement.

    PubMed

    Beall, Reed F; Kuhn, Randall; Attaran, Amir

    2015-03-01

    Compulsory licensing has been widely suggested as a legal mechanism for bypassing patents to introduce lower-cost generic antiretrovirals for HIV/AIDS in developing countries. Previous studies found that compulsory licensing can reduce procurement prices for drugs, but it is unknown how the resulting prices compare to procurements through the Global Fund to Fight AIDS, Tuberculosis, and Malaria; UNICEF; and other international channels. For this study we systematically constructed a case-study database of compulsory licensing activity for antiretrovirals and compared compulsory license prices to those in the World Health Organization's (WHO's) Global Price Reporting Mechanism and the Global Fund's Price and Quality Reporting Tool. Thirty compulsory license cases were analyzed with 673 comparable procurements from WHO and Global Fund data. Compulsory license prices exceeded the median international procurement prices in nineteen of the thirty case studies, often with a price gap of more than 25 percent. Compulsory licensing often delivered suboptimal value when compared to the alternative of international procurement, especially when used by low-income countries to manufacture medicines locally. There is an ongoing need for multilateral and charitable actors to work collectively with governments and medicine suppliers on policy options.

  10. Role of T cell reconstitution in HIV-1 antiretroviral therapy-induced bone loss

    PubMed Central

    Ofotokun, Ighovwerha; Titanji, Kehmia; Vikulina, Tatyana; Roser-Page, Susanne; Yamaguchi, Masayoshi; Zayzafoon, Majd; Williams, Ifor R.; Weitzmann, M. Neale

    2015-01-01

    HIV infection causes bone loss. We previously reported that immunosuppression-mediated B-cell production of receptor activator of NF-κB ligand (RANKL) coupled with decline in osteoprotegerin correlate with decreased bone mineral density (BMD) in untreated HIV-infection. Paradoxically, antiretroviral therapy (ART) worsens bone loss although existing data suggest that such loss is largely independent of specific antiretroviral regimen. This led us to hypothesize that skeletal deterioration following HIV disease reversal with ART may be related to T-cell repopulation and/or immune-reconstitution. Here we transplant T cells into immunocompromised mice to mimic ART-induced T-cell expansion. T-cell reconstitution elicits RANKL and TNFα production by B-cells and/or T-cells, accompanied by enhanced bone resorption and BMD loss. Reconstitution of TNFα- or RANKL-null T-cells and pharmacological TNFα antagonist all protect cortical, but not trabecular bone, revealing complex effects of T-cell-reconstitution on bone turnover. These findings suggest T-cell repopulation and/or immune-reconstitution as putative mechanisms for bone loss following ART initiation. PMID:26392000

  11. Access to highly active antiretroviral therapy for injection drug users: adherence, resistance, and death.

    PubMed

    Vlahov, David; Celentano, David D

    2006-04-01

    Injection drug users (IDUs) continue to comprise a major risk group for HIV infection throughout the world and represent the focal population for HIV epidemics in Asia and Eastern Europe/Russia. HIV prevention programs have ranged from HIV testing and counseling, education, behavioral and network interventions, drug abuse treatment, bleach disinfection of needles, needle exchange and expanded syringe access, as well as reducing transition to injection and primary substance abuse prevention. With the advent of highly active antiretroviral therapy (HAART) in 1996, dramatic clinical improvements have been seen. In addition, the treatment's impact on reducing HIV viral load (and therefore transmission by all routes) provides a stronger rationale for an expansion of the focus on prevention to emphasize early identification and treatment of HIV infected individuals. However, treatment of IDUs has many challenges including adherence, resistance and relapse to high risk behaviors, all of which impact issues of access and ultimately effectiveness of potent antiretroviral treatment. A major current challenge in addressing the HIV epidemic revolves around an appropriate approach to HIV treatment for IDUs.

  12. Persistent Peripheral Nervous System Damage in Simian Immunodeficiency Virus-Infected Macaques Receiving Antiretroviral Therapy.

    PubMed

    Dorsey, Jamie L; Mangus, Lisa M; Hauer, Peter; Ebenezer, Gigi J; Queen, Suzanne E; Laast, Victoria A; Adams, Robert J; Mankowski, Joseph L

    2015-11-01

    Human immunodeficiency virus (HIV)-induced peripheral neuropathy is the most common neurologic complication associated with HIV infection. In addition to virus-mediated injury of the peripheral nervous system (PNS), treatment of HIV infection with combination antiretroviral therapy (cART) may induce toxic neuropathy as a side effect. Antiretroviral toxic neuropathy is clinically indistinguishable from the sensory neuropathy induced by HIV; in some patients, these 2 processes are likely superimposed. To study these intercurrent PNS disease processes, we first established a simian immunodeficiency virus (SIV)/pigtailed macaque model in which more than 90% of animals developed PNS changes closely resembling those seen in HIV-infected individuals with distal sensory neuropathy. To determine whether cART alters the progression of SIV-induced PNS damage, dorsal root ganglia and epidermal nerve fibers were evaluated in SIV-infected macaques after long-term suppressive cART. Although cART effectively suppressed SIV replication and reduced macrophage activation in the dorsal root ganglia, PGP 9.5 immunostaining and measurements of epidermal nerve fibers in the plantar surface of the feet of treated SIV-infected macaques clearly showed that cART did not normalize epidermal nerve fiber density. These findings illustrate that significant PNS damage persists in SIV-infected macaques on suppressive cART.

  13. Sequencing paediatric antiretroviral therapy in the context of a public health approach

    PubMed Central

    Boerma, Ragna S; Boender, T Sonia; van Hensbroek, Michael Boele; Rinke de Wit, Tobias F; Sigaloff, Kim CE

    2015-01-01

    Introduction As access to prevention of mother-to-child transmission (PMTCT) efforts has increased, the total number of children being born with HIV has significantly decreased. However, those children who do become infected after PMTCT failure are at particular risk of HIV drug resistance, selected by exposure to maternal or paediatric antiretroviral drugs used before, during or after birth. As a consequence, the response to antiretroviral therapy (ART) in these children may be compromised, particularly when non-nucleoside reverse transcriptase inhibitors (NNRTIs) are used as part of the first-line regimen. We review evidence guiding choices of first- and second-line ART. Discussion Children generally respond relatively well to ART. Clinical trials show the superiority of protease inhibitor (PI)- over NNRTI-based treatment in young children, but observational reports of NNRTI-containing regimens are usually favourable as well. This is reassuring as national guidelines often still recommend the use of NNRTI-based treatment for PMTCT-unexposed young children, due to the higher costs of PIs. After failure of NNRTI-based, first-line treatment, the rate of acquired drug resistance is high, but HIV may well be suppressed by PIs in second-line ART. By contrast, there are currently no adequate alternatives in resource-limited settings (RLS) for children failing either first- or second-line, PI-containing regimens. Conclusions Affordable salvage treatment options for children in RLS are urgently needed. PMID:26639116

  14. Low bone mass in behaviorally HIV-infected young men on antiretroviral therapy: adolescent trials network (ATN) study 021B

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peak bone mass is achieved in adolescence/early adulthood and is the key determinant of bone mass in adulthood. We evaluated the association of bone mass with HIV infection and antiretroviral therapy (ART) during this critical period among behaviorally HIV infected young men and seronegative control...

  15. Dissemination of Strongyloides stercoralis as an immune restoration phenomenon in an HIV-1-infected man on antiretroviral therapy.

    PubMed

    Brown, M; Cartledge, J D; Miller, R F

    2006-08-01

    We present a case of Strongyloides stercoralis infection in an HIV-infected man, resulting in Escherichia coli meningitis after initiation of antiretroviral therapy. Recent evidence from studies of strongyloides development supports the concept that strongyloides dissemination in this case is an example of an immune reconstitution inflammatory syndrome. PMID:16925906

  16. Gender differences in diet and nutrition among adults initiating antiretroviral therapy in Dar es Salaam, Tanzania.

    PubMed

    Abioye, Ajibola I; Isanaka, Sheila; Liu, Enju; Mwiru, Ramadhani S; Noor, Ramadhani A; Spiegelman, Donna; Mugusi, Ferdinand; Fawzi, Wafaie

    2015-01-01

    Human immunodeficiency virus (HIV)-infected males have poor treatment outcomes after initiation of antiretroviral therapy (ART) compared to HIV-infected women. Dietary factors might mediate the association between sex and disease progression. However, the gender difference in diet among HIV-infected individuals in sub-Saharan Africa is largely unknown. The objective of this study was to examine differences in dietary intake among HIV-infected men and women. We conducted a cross-sectional analysis of dietary questionnaire data from 2038 adults initiating ART in Dar es Salaam, Tanzania to assess whether nutrient adequacy differed by sex. We dichotomized participants' nutrient intakes by whether recommended dietary allowances (RDAs) were met and estimated the relative risk (RR) of meeting RDAs in males using binomial regression models. We also estimated the mean difference in intake of foods and food groups by gender. We found poorer dietary practices among men compared to women. Males were less likely to meet the RDAs for micronutrients critical for slowing disease progression among HIV patients: niacin (RR = 0.39, 95% confidence interval [CI]: 0.27 to 0.55), riboflavin (RR = 0.81, 95% CI: 0.73 to 0.91), vitamin C (RR = 0.94, 95% CI: 0.89 to 1.00), and zinc (RR = 0.06, 95% CI: 0.01 to 0.24). Intake of thiamine, pantothenate, vitamins B6, B12, and E did not vary by gender. Males were less likely to eat cereals (mean difference [servings per day] = -0.21, 95% CI: -0.44 to 0.001) and vegetables (mean difference = -0.47, 95% CI: -0.86 to -0.07) in their diet, but more likely to have meat (mean difference = 0.14, 95% CI: 0.06 to 0.21). We conclude that male HIV patients have poorer dietary practices than females, and this may contribute to faster progression of the disease in males.

  17. Lipodystrophy in Human Immunodeficiency Virus (HIV) Patients on Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Kumar, N. Sunil; Shashibhushan, J.; Venugopal, K.; Vishwanatha, Huggi; Menon, Mahesh

    2015-01-01

    Background In recent years, abnormal lipid deposition (both lipoatrophy and fat redistribution) and its related complications have changed from an anecdotal issue into a major problem for HIV (Human Immunodeficiency Virus) infected patients on HAART (Highly Active Anti-Retroviral Therapy). Lipoatrophy and fat redistribution are potentially stigmatizing complications of HAART and leads to poor adherence among patients. Hence we conducted this study to determine the pattern and to assess various risk factors for maldeposition of lipids in HIV patients. Materials and Methods A cross-sectional case series study was conducted in ART PLUS centre, Bellary over a period of 8 months from January to August 2014 in HIV patients on ART to determine risk factors associated with and epidemiological pattern of fat redistribution or atrophy. Results A total of 50 patients with LD {lipodystrophy} (26 with fat redestribution and 24 with lipoatrophy {LA} were diagnosed in this period. Most of them belonged to younger age and was commonly seen in females (76%). Patients with LA had a significantly lower BMI (18.73 ± 7.4), {the p-value being 0.19} compared to LH group (21.54 ± 7.62). The duration of disease was comparable among both groups (6.96 years in LH and 5.79 years in LA group) {p-value is 0.29}. There was a relatively good immunity among these patients with mean CD4 count was 509.23 in LH and 545.91 in LA group {single CD4 count was taken and the p-value was 0.001}. Most of the patients were in TLN (Tenofovir, Lamivudine, Nevirapine) regimen (58%).The duration that patient was on ART before commencement of study varied from patient to patient, but the mean duration was approximately five years in fat redistribution group and 4.5 years in LA group. There were no derangements in lipid and sugar levels among them. Conclusion This study shows the need to identify and impact of LD with respect to treatment adherence in young patients especially female patients. Early community

  18. Hypertension among HIV-Infected Adults Receiving Highly Active Antiretroviral Therapy (HAART) in Malaysia

    PubMed Central

    Hejazi, Nazisa; MSL, Huang; Lin, Khor Geok; Choong, Lee Christopher Kwok

    2014-01-01

    There are increasing researches about non-communicable disease such as elevated blood pressure among people living with HIV before and after initiation of highly active antiretroviral therapy (HAART). This cross-sectional study was designed to determine the prevalence of hypertension and associated risk factors among 340 HIV-infected patients on antiretroviral therapy at a Malaysian public hospital providing HIV-related treatment. Data on socioeconomic background, anthropometry, medical history and dietary intake of the patients were collected. Hypertension is defined as blood pressure ≥130/85 (mm Hg). Prevalence of hypertension was 45.60% (n=155) of which 86.5% of the hypertensive group were male (n=134). The results showed that increase in age (OR 1.051, 95% confidence interval (CI) 1.024-1.078), higher body mass index (OR 1.18, 95% CI 1.106-2.71), bigger waist circumference (OR 1.18, 95%CI 1.106-2.71), higher waist-hip ratio (OR 1.070, 95%CI 1.034-1.106), higher fasting plasma glucose (OR 1.332, 95% CI 0.845-2.100) and percentage energy intake from protein >15 (OR 2.519, 95%CI 1.391-4.561) were significant risk factors for hypertension (p<0.001). After adjusting for other variables, increasing age (adjusted odds ratio (aOR) 1.069 95%CI 1.016-1.124, p=0.010), being male (aOR 3.026, 95%CI 1.175-7.794, p=0.022) and higher body mass index (aOR 1.26, 95%CI 1.032-1.551, p=0.024) were independently associated with hypertension. None of the antiretroviral therapy and immunologic factors was linked to hypertension. In conclusion hypertension among PLHIV was linked to the well-known risk factors such as age, gender and body mass index. With HAART, people can live longer by making monitoring and control of some reversible factors, especially excessive weight gain for maintaining quality of life. PMID:24576366

  19. Long-Term Outcomes on Antiretroviral Therapy in a Large Scale-Up Program in Nigeria

    PubMed Central

    Meloni, Seema T.; Chang, Charlotte A.; Eisen, Geoffrey; Jolayemi, Toyin; Banigbe, Bolanle; Okonkwo, Prosper I.; Kanki, Phyllis J.

    2016-01-01

    Background While there has been a rapid global scale-up of antiretroviral therapy programs over the past decade, there are limited data on long-term outcomes from large cohorts in resource-constrained settings. Our objective in this evaluation was to measure multiple outcomes during first-line antiretroviral therapy in a large treatment program in Nigeria. Methods We conducted a retrospective multi-site program evaluation of adult patients (age ≥15 years) initiating antiretroviral therapy between June 2004 and February 2012 in Nigeria. The baseline characteristics of patients were described and longitudinal analyses using primary endpoints of immunologic recovery, virologic rebound, treatment failure and long-term adherence patterns were conducted. Results Of 70,002 patients, 65.2% were female and median age was 35 (IQR: 29–41) years; 54.7% were started on a zidovudine-containing and 40% on a tenofovir-containing first-line regimen. Median CD4+ cell counts for the cohort started at 149 cells/mm3 (IQR: 78–220) and increased over duration of ART. Of the 70,002 patients, 1.8% were reported as having died, 30.1% were lost to follow-up, and 0.1% withdrew from treatment. Overall, of those patients retained and with viral load data, 85.4% achieved viral suppression, with 69.3% achieving suppression by month 6. Of 30,792 patients evaluated for virologic failure, 24.4% met criteria for failure and of 45,130 evaluated for immunologic failure, 34.0% met criteria for immunologic failure, with immunologic criteria poorly predicting virologic failure. In adjusted analyses, older age, ART regimen, lower CD4+ cell count, higher viral load, and inadequate adherence were all predictors of virologic failure. Predictors of immunologic failure differed slightly, with age no longer predictive, but female sex as protective; additionally, higher baseline CD4+ cell count was also predictive of failure. Evaluation of long-term adherence patterns revealed that the majority of patients

  20. Tuberculosis After One Year of Combination Antiretroviral Therapy in Nigeria: A Retrospective Cohort Study

    PubMed Central

    Achenbach, Chad J.; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T.; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L.

    2013-01-01

    Abstract Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm3 and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm3 and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count <350 cells/mm3 and HIV-1 RNA level ≤400 copies/ml (group 3), and CD4 T cell count <350 cells/mm3 and HIV-1 RNA level >400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan–Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97–4.61), 2.05 (95% CI 1.10–3.79), and 3.65 (95% CI 1.15–5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population. PMID:23316724

  1. Tuberculosis after one year of combination antiretroviral therapy in Nigeria: a retrospective cohort study.

    PubMed

    Akanbi, Maxwell O; Achenbach, Chad J; Feinglass, Joe; Taiwo, Babafemi; Onu, Adamu; Pho, Mai T; Agbaji, Oche; Kanki, Phyllis; Murphy, Robert L

    2013-06-01

    Our objective was to determine tuberculosis (TB) incidence and evaluate TB risk in adults after one or more years of use of combination antiretroviral therapy (cART) through a retrospective cohort study in Jos, Nigeria. We studied a cohort of HIV-infected adults treated with ART for at least 1 year. Based on immunologic and virologic responses to ART, patients were categorized into four groups: CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 1), CD4 T cell count ≥350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 2), CD4 T cell count <350 cells/mm(3) and HIV-1 RNA level ≤400 copies/ml (group 3), and CD4 T cell count <350 cells/mm(3) and HIV-1 RNA level >400 copies/ml (group 4). Time to incident TB for the four groups was analyzed using the Kaplan-Meier method. Cox regression models were used to evaluate predictors of incident TB. In this cohort of 5,093 HIV-infected adults, of which 68.4% were female, with a mean age 35.1 years (standard deviation 9.1 years), we observed 98 cases of incident TB during 4 years and 3 months of follow-up. The overall TB incidence rate was 8.7 cases/1,000 patient-years of follow-up. Adjusted hazards for incident TB were 2.11 (95% CI 0.97-4.61), 2.05 (95% CI 1.10-3.79), and 3.65 (95% CI 1.15-5.06) in group 2, 3, and 4 patients, respectively, compared to group 1. Tuberculosis incidence in patients on ART is driven by poor immunologic and/or virologic response. Optimization of HIV treatment should be prioritized to reduce the burden of TB in this high-risk population.

  2. Virtual Intervention to Support Self-Management of Antiretroviral Therapy Among People Living With HIV

    PubMed Central

    Godin, Gaston; Ramirez-Garcia, Pilar; Rouleau, Geneviève; Bourbonnais, Anne; Guéhéneuc, Yann-Gaël; Tremblay, Cécile; Otis, Joanne

    2015-01-01

    Background Living with human immunodeficiency virus (HIV) necessitates long-term health care follow-up, particularly with respect to antiretroviral therapy (ART) management. Taking advantage of the enormous possibilities afforded by information and communication technologies (ICT), we developed a virtual nursing intervention (VIH-TAVIE) intended to empower HIV patients to manage their ART and their symptoms optimally. ICT interventions hold great promise across the entire continuum of HIV patient care but further research is needed to properly evaluate their effectiveness. Objective The objective of the study was to compare the effectiveness of two types of follow-up—traditional and virtual—in terms of promoting ART adherence among HIV patients. Methods A quasi-experimental study was conducted. Participants were 179 HIV patients on ART for at least 6 months, of which 99 were recruited at a site offering virtual follow-up and 80 at another site offering only traditional follow-up. The primary outcome was medication adherence and the secondary outcomes were the following cognitive and affective variables: self-efficacy, attitude toward medication intake, symptom-related discomfort, stress, and social support. These were evaluated by self-administered questionnaire at baseline (T0), and 3 (T3) and 6 months (T6) later. Results On average, participants had been living with HIV for 14 years and had been on ART for 11 years. The groups were highly heterogeneous, differing on a number of sociodemographic dimensions: education, income, marital status, employment status, and living arrangements. Adherence at baseline was high, reaching 80% (59/74) in the traditional follow-up group and 84% (81/97) in the virtual follow-up group. A generalized estimating equations (GEE) analysis was run, controlling for sociodemographic characteristics at baseline. A time effect was detected indicating that both groups improved in adherence over time but did not differ in this regard

  3. [Dietary intake and dyslipidemia arising from combination antiretroviral therapy for HIV infection: a systematic review].

    PubMed

    Almeida, Luara Bellinghausen; Giudici, Kelly Virecoulon; Jaime, Patricia Constante

    2009-07-01

    To review and synthesize the available scientific evidence on the relationship between dietary intake and dyslipidemias in HIV-infected patients in combination antiretroviral therapy (ART). A systematic review of literature was carried out. Original and published studies were investigated and two categories of dietary exposure were considered: energy and nutrient intake, and consumption of a test diet. A narrative review of included studies was conducted. The findings were summarized according to category of metabolic outcomes (effect on total cholesterol and LDL-c, effect on HDL-c and effect on triglycerides). Twenty original studies were included in this review, being 13 clinical trials and 7 observational studies. Omega-3 fatty acid supplementation led to a significant decrease in triglycerides. There was very little evidence on the effectiveness of dietary interventions for the prevention and control of dyslipidemias in HIV-infected patients receiving ART.

  4. Preferences for characteristics of antiretroviral therapy provision in Johannesburg, South Africa: results of a conjoint analysis.

    PubMed

    Opuni, Marjorie; Bishai, David; Gray, Glenda E; McIntyre, James A; Martinson, Neil A

    2010-08-01

    A survey was administered to HIV-infected patients and a sample in Soweto and the Johannesburg inner city to measure preferences for antiretroviral therapy (ART) provision. The 25 to 49-year-old male and female respondents viewed 20 sets of three hypothetical ART clinic choices after reading information on ART. Each set had a permutation of four levels of: monthly ART price, clinic waiting times, HIV clinic branding and clinic staff attitudes. For each set, respondents selected the preferred mix of characteristics and indicated if they would pay for it. For every ZAR 100 (USD PPP 25) increase in price, the average probability of selecting a clinic decreased by 2.8 and 3.0% in the HIV patient and household samples, respectively. Cost as well as staff attitude, wait time, and clinic branding may constitute important barriers to ART uptake and adherence in resource-poor settings.

  5. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients. PMID:15255240

  6. Decreased HIV Type 1 Transcription in CCR5-Δ32 Heterozygotes During Suppressive Antiretroviral Therapy

    PubMed Central

    Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C.; Lada, Steven M.; Yukl, Steven; Cockerham, Leslie R.; Pilcher, Christopher D.; Hecht, Frederick M.; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D.; Deeks, Steven G.; Pillai, Satish K.

    2014-01-01

    Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P = .035), RNA to DNA transcriptional ratios (P = .013), and frequency of detectable HIV 2–long terminal repeat circular DNA (P = .013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2 = 0.136; P = .002). Our findings suggest that curative strategies should further explore manipulation of CCR5. PMID:24935955

  7. Clinician Perspectives on Delaying Initiation of Antiretroviral Therapy for Clinically Eligible HIV-Infected Patients

    PubMed Central

    Valverde, Eduardo E.; Raiford, Jerris L.; Weiser, John; White, Becky L.; Skarbinski, Jacek

    2015-01-01

    Objectives: Guidelines for antiretroviral therapy (ART) initiation have evolved, but consistently note that adherence problems should be considered and addressed. Little is known regarding the reasons providers delay ART initiation in clinically eligible patients. Methods: In 2009, we surveyed a probability sample of HIV care providers in 582 outpatient facilities in the United States and Puerto Rico with an open-ended question about nonclinical reasons for delaying ART initiation in otherwise clinically eligible patients. Results: Very few providers (2%) reported never delaying ART. Reasons for delaying ART were concerns about patient adherence (68%), patient acceptance (60%), and structural barriers (33%). Provider and practice characteristics were associated with reasons for delaying ART. Conclusion: Reasons for delaying ART were consistent with clinical guidelines and were both patient level and structural. Providers may benefit from training and access to referrals for ancillary services to enhance their ability to monitor and address these issues with their patients. PMID:25394912

  8. Preferences for characteristics of antiretroviral therapy provision in Johannesburg, South Africa: results of a conjoint analysis.

    PubMed

    Opuni, Marjorie; Bishai, David; Gray, Glenda E; McIntyre, James A; Martinson, Neil A

    2010-08-01

    A survey was administered to HIV-infected patients and a sample in Soweto and the Johannesburg inner city to measure preferences for antiretroviral therapy (ART) provision. The 25 to 49-year-old male and female respondents viewed 20 sets of three hypothetical ART clinic choices after reading information on ART. Each set had a permutation of four levels of: monthly ART price, clinic waiting times, HIV clinic branding and clinic staff attitudes. For each set, respondents selected the preferred mix of characteristics and indicated if they would pay for it. For every ZAR 100 (USD PPP 25) increase in price, the average probability of selecting a clinic decreased by 2.8 and 3.0% in the HIV patient and household samples, respectively. Cost as well as staff attitude, wait time, and clinic branding may constitute important barriers to ART uptake and adherence in resource-poor settings. PMID:19533322

  9. Antiretroviral Therapy and Nutrition in Southern Africa: Citizenship and the Grammar of Hunger.

    PubMed

    Cousins, Thomas

    2016-01-01

    How might we understand and respond to the new forms of hunger that arise with the massive rollout of antiretroviral therapy (ART) for HIV in southern Africa? Rather than 'merely' a technical problem of measurement, medicine or infrastructure, I suggest that a philosophical question arises concerning the relationship between the experience of hunger, the utterances that communicate that experience, and the bodily regimes of well-being and ill-being indexed by such utterances. Taking the gut as a particular kind of mediator of experience, I draw on ethnographic fieldwork conducted in KwaZulu-Natal, South Africa to open up a set of questions on acknowledgment and avoidance. The central question concerns the divergent concepts of 'grammar' that confront the relationship between hunger and ART.

  10. Health literacy and adherence to antiretroviral therapy among HIV-infected youth.

    PubMed

    Navarra, Ann-Margaret; Neu, Natalie; Toussi, Sima; Nelson, John; Larson, Elaine L

    2014-01-01

    Health literacy has been associated with adherence to antiretroviral therapy (ART) in HIV-infected adults, but this association has not been demonstrated in HIV-infected adolescents. Using an expanded health literacy model, we examined the relationship between health literacy, functional literacy, beliefs about ART, media use, and adherence to ART. A convenience sample of HIV-infected adolescents (n = 50) was recruited for this cross-sectional study. The primary outcome of adherence was measured with 3-day self-reports. Health literacy as measured by the Test of Functional Health Literacy in Adults (TOFHLA) was not predictive of adherence (p = .15). Participants with higher positive outcome expectancy scores regarding ART were more likely to report 100% adherence, and participants with below-grade-level reading were less likely to report 100% adherence (p < .05). Our findings highlight the importance of assessing both health beliefs and reading skills as part of adherence support for HIV-infected youth.

  11. Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi.

    PubMed

    Kanyerere, H; Mganga, A; Harries, A D; Tayler-Smith, K; Jahn, A; Chimbwandira, F M; Mpunga, J

    2014-06-21

    From 2000 to 2012, Malawi scaled up antiretroviral therapy (ART) from <3000 to 404 905 persons living with HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome), representing an ART coverage of 40.6% among those living with HIV. During this time, annual tuberculosis (TB) notifications declined by 28%, from 28 234 to 20 463. Percentage declines in annual TB case notifications were as follows: new TB (26%), recurrent TB (40%), new smear-positive pulmonary TB (19%), new smear-negative pulmonary TB (42%), extra-pulmonary TB (19%), HIV-positive TB (30%) and HIV-negative TB (10%). The decline in TB notifications is associated with ART scale-up, supporting its value in controlling TB in high HIV prevalence areas in sub-Saharan Africa.

  12. Enhancing the benefits of antiretroviral therapy in Vietnam: towards ending AIDS.

    PubMed

    Kato, Masaya; Long, Nguyen Hoang; Duong, Bui Duc; Nhan, Do Thi; Nguyen, Thi Thuy Van; Hai, Nguyen Huu; Giang, Le Minh; Hoa, Do Mai; Van, Nguyen Thanh; Suthar, Amitabh B; Fontaine, Chris; Nadol, Patrick; Lo, Ying-Ru; McConnell, Michelle S

    2014-12-01

    Vietnam has a concentrated HIV epidemic, with the highest HIV prevalence being observed among people who inject drugs (PWID). Based on its experience scaling-up robust HIV interventions, Vietnam aims to further strengthen its response by harnessing the preventive benefits of antiretroviral therapy (ART). Mathematical modelling suggests that prioritizing key populations for earlier access to ART, combined with other prevention interventions, may have significant impact on the epidemic, cost-effectively reducing new HIV infections and deaths. Pilot studies are being conducted to assess feasibility and acceptability of expansion of HIV testing and counselling (HTC) and early ART among key populations and to demonstrate innovative service delivery models to address challenges in uptake of services across the care cascade. Earlier access of key populations to combination prevention interventions, combined with sustained political commitment and supportive environment for key populations, are essential for maximum impact of ART on the HIV epidemic in Vietnam.

  13. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

  14. Anxiety and depression symptoms as risk factors for non-adherence to antiretroviral therapy in Brazil.

    PubMed

    Campos, Lorenza Nogueira; Guimarães, Mark Drew Crosland; Remien, Robert H

    2010-04-01

    Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n = 293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH = 1.87; 95% CI = 1.14-3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life.

  15. Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy.

    PubMed

    Wang, Charlene; Abdel-Mohsen, Mohamed; Strain, Matthew C; Lada, Steven M; Yukl, Steven; Cockerham, Leslie R; Pilcher, Christopher D; Hecht, Frederick M; Sinclair, Elizabeth; Liegler, Teri; Richman, Douglas D; Deeks, Steven G; Pillai, Satish K

    2014-12-01

    Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.

  16. Decline in national tuberculosis notifications with national scale-up of antiretroviral therapy in Malawi

    PubMed Central

    Kanyerere, H.; Mganga, A.; Tayler-Smith, K.; Jahn, A.; Chimbwandira, F. M.; Mpunga, J.

    2014-01-01

    From 2000 to 2012, Malawi scaled up antiretroviral therapy (ART) from <3000 to 404 905 persons living with HIV/AIDS (human immunodeficiency virus/acquired immune-deficiency syndrome), representing an ART coverage of 40.6% among those living with HIV. During this time, annual tuberculosis (TB) notifications declined by 28%, from 28 234 to 20 463. Percentage declines in annual TB case notifications were as follows: new TB (26%), recurrent TB (40%), new smear-positive pulmonary TB (19%), new smear-negative pulmonary TB (42%), extra-pulmonary TB (19%), HIV-positive TB (30%) and HIV-negative TB (10%). The decline in TB notifications is associated with ART scale-up, supporting its value in controlling TB in high HIV prevalence areas in sub-Saharan Africa. PMID:26399210

  17. Factors impacting the provision of antiretroviral therapy to people living with HIV: the view from Haiti.

    PubMed

    Rouzier, Vanessa; Farmer, Paul E; Pape, Jean W; Jerome, Jean-Gregory; Van Onacker, Joelle Deas; Morose, Willy; Joseph, Patrice; Leandre, Fernet; Severe, Patrice; Barry, Donna; Deschamps, Marie-Marcelle; Koenig, Serena P

    2014-01-01

    Haiti is the poorest country in the Western Hemisphere and has the highest number of people living with HIV in the Caribbean, the region most impacted by HIV outside of Africa. Despite continuous political, socioeconomic and natural catastrophes, Haiti has mounted a very successful response to the HIV epidemic. Prevention and treatment strategies implemented by the government in collaboration with non-governmental organizations have been instrumental in decreasing the national HIV prevalence from a high of 6.2% in 1993 to 2.2% in 2012. We describe the history and epidemiology of HIV in Haiti and the expansion of antiretroviral therapy (ART) over the past decade, with the achievement of universal access to ART for patients meeting the 2010 World Health Organization guidelines. We also describe effective models of care, successes and challenges of international funding, and current challenges in the provision of ART. We are optimistic that the goal of providing ART for all in need remains in reach.

  18. Depression, substance abuse and other contextual predictors of adherence to antiretroviral therapy (ART) among Haitians.

    PubMed

    Malow, Robert; Dévieux, Jessy G; Stein, Judith A; Rosenberg, Rhonda; Jean-Gilles, Michele; Attonito, Jennifer; Koenig, Serena P; Raviola, Giuseppe; Sévère, Patrice; Pape, Jean W

    2013-05-01

    Haiti has the highest number of individuals living with HIV in the Caribbean. Due to Haiti's resource-poor environment and inadequate mental health and substance abuse services, adherence to antiretroviral therapy (ART) may be especially difficult. This study examined associations among demographics, maladaptive coping, partner conflict, alcohol problems, depression, and negative attitudes about medications and their impact on adherence among 194 HIV-positive Haitians. In a mediated directional structural equation model, depression and negative attitudes about ART directly predicted poorer adherence. Greater partner conflict, maladaptive coping and alcohol problems predicted more depression. Maladaptive coping predicted a negative attitude about ART. Alcohol problems predicted partner conflict and maladaptive coping. Significant indirect effects on adherence mediated through both depression and negative attitudes about ART include negative effects of female gender, alcohol problems and maladaptive coping. Results highlight the importance of integrated care for depression, alcohol use and other psychosocial problems to increase ART adherence.

  19. Highly active antiretroviral therapy-related mechanisms of endothelial and platelet function alterations.

    PubMed

    Gresele, Paolo; Falcinelli, Emanuela; Momi, Stefania; Francisci, Daniela; Baldelli, Franco

    2014-01-01

    Highly active antiretroviral therapy (HAART) has transformed human immunodeficiency virus (HIV) infection into a chronic condition, which has allowed the infected population to age and become prone to chronic degenerative diseases common to the general population, including atherosclerotic cardiovascular disease, and coronary artery disease (CAD). Possible causative mechanisms of HIV-associated CAD are related to classic cardiovascular risk factors, such as dyslipidemia, insulin resistance, and fat redistribution, which may be due to either HIV infection or to HAART-associated toxicity. However, other mechanisms are emerging as crucial for the cardiovascular complication of HIV and HAART. This article analyzes the effects of HIV and HAART on endothelial function, endothelium-leukocyte interactions, and platelets as possible mechanisms of enhanced cardiovascular risk.

  20. [Effect of triple antiretroviral therapy on Tunisian AIDS profile: study of 139 cases].

    PubMed

    Zouiten, Fayçal; Ammari, Lamia; Goubantini, Ahmed; Tiouiri, Hanène; Slim, Amine; Maamouri, Ahmed; Kilani, Badreddine; Kanoun, Fakher; Marrakchi, Chekib; Neifer, Nahed; Mihoub, Leila; Jenhani, Faouzi; Garbouj, Mounira; Ben Chaabane, Taoufik

    2003-12-01

    We report a retrospective study to estimate highly active antiretroviral therapy (HAART) effect in 139 HIV infected patients. Four criteria are studied: prevalence of opportunistic infections, CD4 cell count evolution, viral load progression and mortality. Gastrointestinal side effects are the most common clinical adverse reaction (61.1 percent), and hematological side effects are the most common biological adverse reaction (61.2 percent). During the 22.8 months (3 months to 6 years) follow-up average period, CD4 cell counts remained above 500 per cubic millimeter in only 25.8 percent of cases, while 63.5 percent of patients had a viral load below 400 copies per milliliter. During the study on patients receiving HAART, opportunistic infections appeared in 17.3 percent of cases (24 cases) and mortality in 6.4 percent of cases.

  1. Cognitive functioning during highly active antiretroviral therapy interruption in human immunodeficiency virus type 1 infection.

    PubMed

    Childers, Meredith E; Woods, Steven Paul; Letendre, Scott; McCutchan, J Allen; Rosario, Debralee; Grant, Igor; Mindt, Monica Rivera; Ellis, Ronald J

    2008-11-01

    Although no longer considered therapeutically beneficial, antiretroviral treatment interruptions (TIs) still occur frequently among patients with human immunodeficiency virus (HIV) infection for a variety of reasons. TIs typically result in viral rebound and worsening immunosuppression, which in turn are risk factors for neurocognitive decline and dementia. We sought to determine the extent of neurocognitive risk with TIs and subsequent reintroduction of highly active antiretroviral therapy (HAART) by using a comprehensive, sensitive neuropsychological assessment and by concurrently determining changes in plasma and cerebrospinal fluid (CSF) viral load and CD4 counts. Prospective, serial, clinical evaluations including neuropsychological (NP) testing and measurement of plasma HIV RNA and CD4 count and mood state were performed on HIV-1-infected individuals (N=11) at three time points: (1) prior to a TI, while on HAART; (2) after TIs averaging 6 months; and (3) after reinitiating HAART therapy. During TI, plasma HIV RNA increased and CD4 counts declined significantly, but NP performance did not change. Following reinitiation of HAART, viral loads fell below pre-TI levels, and CD4 counts rose. Improved viral suppression and immune restoration with reinitiation of HAART resulted in significant improvement in neurocognitive performance. No changes on comprehensive questionnaires of mood state were observed in relation to TI.NP performance and mood state remained stable during TIs despite worsened viral loads and CD4 counts. Because "practice effects" are generally greatest between the first and second NP testing sessions, improvement at the third, post-TI time point was unlikely to be accounted for by practice. TIs of up to 6 months appear to be neurocognitively and psychiatrically safe for most patients.

  2. Increased antiretroviral therapy prescription and HIV viral suppression among persons receiving clinical care for HIV infection

    PubMed Central

    Bradley, Heather; Mattson, Christine L.; Beer, Linda; Huang, Ping; Shouse, R. Luke

    2016-01-01

    Objective To assess trends during 2009–2013 in antiretroviral therapy (ART) prescription and viral suppression among adults receiving HIV clinical care in the United States. Design We used data from the Medical Monitoring Project, a surveillance system producing national estimates of characteristics of HIV-infected adults receiving clinical care in the United States. Methods We estimated weighted proportions of persons receiving HIV medical care who were prescribed ART and achieved HIV viral suppression (<200 copies/ml) at both last test and at all tests in the previous 12 months during 2009–2013. We assessed trends overall and by gender, age, race/ethnicity, and sexual behavior/orientation. Results ART prescription and viral suppression increased significantly during 2009–2013, overall and in subgroups. ART prescription increased from 89 to 94% (P for trend <0.01). Viral suppression at last measurement increased from 72 to 80% (P for trend <0.01). The largest increases were among 18–29 year olds (56–68%), 30–39 year olds (62–75%), and non-Hispanic blacks (64–76%). Sustained viral suppression increased from 58 to 68% (P for trend <0.01). The largest increases were among 18–29 year olds (32–51%), 30–39 year olds (47–63%), and non-Hispanic blacks (49–61%). Conclusion Adults receiving HIV medical care are increasingly likely to be prescribed ART and achieve viral suppression. Recent efforts to promote early antiretroviral therapy use may have contributed to these increases, bringing us closer to realizing key goals of the National HIV/AIDS Strategy. PMID:27465279

  3. HIV-Associated Lung Cancer in the Era of Highly Active Antiretroviral Therapy (HAART)

    PubMed Central

    Pakkala, Suchita; Chen, Zhengjia; Rimland, David; Owonikoko, Taofeek K.; Gunthel, Clifford; Brandes, Johann R.; Saba, Nabil R.; Shin, Dong M.; Curran, Walter J.; Khuri, Fadlo R.; Ramalingam, Suresh S.

    2011-01-01

    Background Lung cancer is the leading cause of death among non-acquired immunodeficiency syndrome (AIDS) defining malignancies. Since highly active anti-retroviral therapy (HAART) has improved survival for human immunodeficiency virus (HIV) patients, we evaluated lung cancer outcomes in the HAART era. Methods HIV-positive patients diagnosed with lung cancer in our institution during the HAART era (1995-2008) were analyzed. Patient charts were reviewed for clinical and laboratory data. CD4 count at diagnosis was treated as a continuous variable and subcategorized into distinct variables with 3 cut-off points (50, 200, & 500 μl). Pearson’s correlation coefficients were estimated for each covariate studied. Survival was determined by the Kaplan-Meier method. Results Out of 80 patients, 73 had non-small cell lung cancer. Baseline characteristics were: median age-52 yrs; male-80%; African American-84%; injection drug use-25%; smokers-100%; and prior exposure to antiretroviral agents-55%. Mean CD4 count and viral load were 304 μL and 82,420 copies/ml, respectively at cancer diagnosis. The latency between diagnosis of HIV and lung cancer was significantly shorter in women (4.1 yrs vs. 7.7 yrs, P=0.02) and 71% of the patients received anti-cancer therapy. The 1- and 3-year survival rates were 31% and 4% overall. Grade 3/4 toxicities occurred in 60% with chemo-radiation vs. 36% with chemotherapy. Cancer-related survival was better for patients with CD4 count >200 (P=0.0298) and >500 (P=0.0076). Conclusions The latency from diagnosis of HIV to lung cancer was significantly shorter for women. Although outcomes for lung cancer patients with HIV remain poor, high CD4 count is associated with an improved lung cancer-related survival. PMID:21713759

  4. Improved Adherence to Modern Antiretroviral Therapy among HIV Infected Injection Drug Users

    PubMed Central

    Mann, Bikaramjit; Milloy, M-J; Kerr, Thomas; Zhang, Ruth; Montaner, Julio; Wood, Evan

    2012-01-01

    Objectives Adherence to antiretroviral therapy (ART) among injection drug users (IDU) is often sub-optimal, yet little is known about changes in patterns of adherence since the advent of highly active antiretroviral therapy in 1996. We sought to assess levels of optimal adherence to ART among IDU in a setting of free and universal HIV care. Methods Data was collected through a prospective cohort study of HIV-positive IDU in Vancouver, British Columbia. We calculated the proportion of individuals achieving at least 95% adherence in the year following initiation of ART from 1996 to 2009. Results Among 682 individuals who initiated ART, the median age was 37 (31–44) years with 248 (36.4%) female participants. The proportion achieving at least 95% adherence increased over time from 19.3% in 1996 to 65.9% in 2009 (Cochrane-Armitage test for trend: p < 0.001). In a logistic regression model examining factors associated with 95% adherence, initiation year was statistically significant (Odds Ratio = 1.08, 95% Confidence Interval: 1.03–1.13, p < 0.001 per year after 1996) after adjustment for a range of drug use variables and other potential confounders. Conclusions The proportion of IDU achieving at least 95% adherence during the first year of ART has consistently increased over a 13-year period. Although improved tolerability and convenience of modern ART regimens likely explain these positive trends, by the end of the study period a substantial proportion of IDU still had sub-optimal adherence demonstrating the need for additional adherence support strategies. PMID:22551168

  5. Facilitators and barriers to antiretroviral therapy adherence among adolescents in Ghana

    PubMed Central

    Ankrah, Daniel NA; Koster, Ellen S; Mantel-Teeuwisse, Aukje K; Arhinful, Daniel K; Agyepong, Irene A; Lartey, Margaret

    2016-01-01

    Introduction Adherence to antiretroviral therapy (ART) is known to be challenging among adolescents living with HIV/AIDS, notwithstanding the life-saving importance of this therapy. Of the global total number of adolescents living with HIV in 2013, 83% reside in sub-Saharan Africa. The study aimed to identify facilitators of and barriers to antiretroviral treatment adherence among adolescents in Ghana. Methods A cross-sectional qualitative study using semi-structured interviews for data collection was carried out among adolescents (aged 12–19 years) at the adolescents HIV clinic at the Korle-Bu Teaching Hospital in Ghana. Predominantly open-ended questions relating to ART were used. Interviews were done until saturation. In total, 19 interviews were conducted. Analysis was done manually to maintain proximity with the text. Findings The main facilitators were support from health care providers, parental support, patient’s knowledge of disease and self-motivation, patient’s perceived positive outcomes, and dispensed formulation. The identified barriers were patient’s forgetfulness to take medicines, perceived stigmatization due to disclosure, financial barriers, and adverse effects of ART. Support from health care workers was the most frequently mentioned facilitator, and patient’s forgetfulness and perceived stigmatization after disclosure were the most frequently mentioned barriers. Self-motivation (knowledge induced) to adhere to treatment was a specific facilitator among older adolescents. Conclusion Continuous information provision in addition to unflinching support from health care workers and parents or guardians may improve adherence among adolescents. Also, interventions to reduce patient forgetfulness may be beneficial. A multi-sectorial approach would be needed to address adolescent disclosure of HIV/AIDS status. PMID:27042024

  6. Use of new antiretroviral drugs and classes in Bahia, Brazil: a real life experience on salvage therapy of AIDS patients.

    PubMed

    Brites, Carlos; Nóbrega, Isabella; Martins Netto, Eduardo

    2015-01-01

    Antiretroviral therapy has significantly evolved in the last decade, with an increasing number of new drugs and classes. Currently, even heavily experienced patients can be successfully treated with new regimens. In Brazil, the recent incorporation of some new antiretroviral drugs made it possible to suppress HIV plasma viremia in most treated patients, with significant benefits in terms of quality of life and survival. However, little has been published on outcomes of patients under new drugs-based regimens. We reviewed the safety and efficacy of antiretroviral regimens using recently introduced drugs in Bahia. Our results confirm that patients using darunavir, raltegravir, enfuvirtide, or etravirine presented with a high rate of virological suppression without significant adverse events, after one year of follow-up.

  7. Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

    PubMed Central

    Périssé, André R. S.; Smeaton, Laura; Chen, Yun; La Rosa, Alberto; Walawander, Ann; Nair, Apsara; Grinsztejn, Beatriz; Santos, Breno; Kanyama, Cecilia; Hakim, James; Nyirenda, Mulinda; Kumarasamy, Nagalingeswaran; Lalloo, Umesh G.; Flanigan, Timothy; Campbell, Thomas B.; Hughes, Michael D.

    2013-01-01

    Background Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study. Methods Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen. Results 31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death. Conclusions Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients. PMID:24391801

  8. Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review.

    PubMed

    Katusiime, Christine; Ocama, Ponsiano; Kambugu, Andrew

    2014-09-01

    The effectiveness of combination antiretroviral therapy (cART) continues to improve as treatment choices expand with the development of new antiretroviral agents and regimens. However, the successful long-term treatment of HIV/AIDS is under threat from the emergence of drug-resistant strains to multiple agents and entire drug classes.

  9. Comparison of efavirenz and protease inhibitor based combination antiretroviral therapy regimens in treatment-naïve people living with HIV with baseline resistance.

    PubMed

    Lim, Charlotte; McFaul, Katie; Kabagambe, Samuel; Sonecha, Sonali; Jones, Rachael; Asboe, David; Pozniak, Anton; Nwokolo, Nneka; Boffito, Marta

    2016-07-17

    A retrospective cohort analysis comparing the efficacy of boosted protease inhibitor-based and efavirenz-based combination antiretroviral therapy in treatment-naïve people living with HIV with baseline resistance found that efavirenz-based treatment led to a shorter mean time to undetectable viral load. A higher proportion of patients with nonnucleoside reverse transcriptase inhibitor related baseline resistance mutations in the efavirenz-treatment group achieved an undetectable viral load at both 6 and 12 months post-treatment initiation, compared with the boosted protease-inhibitor-treatment group.Supplementary content: http://links.lww.com/QAD/A930. PMID:27139315

  10. Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A Review

    PubMed Central

    Moog, Claude H.; Stan, Guy-Bart; Brunet, Cecile; Raffi, François; Ferré, Virginie; Costanza, Vicente; Mhawej, Marie J.; Biafore, Federico; Ouattara, Djomangan A.; Ernst, Damien; Fonteneau, Raphael; Xia, Xiaohua

    2014-01-01

    Abstract This review shows the potential ground-breaking impact that mathematical tools may have in the analysis and the understanding of the HIV dynamics. In the first part, early diagnosis of immunological failure is inferred from the estimation of certain parameters of a mathematical model of the HIV infection dynamics. This method is supported by clinical research results from an original clinical trial: data just after 1 month following therapy initiation are used to carry out the model identification. The diagnosis is shown to be consistent with results from monitoring of the patients after 6 months. In the second part of this review, prospective research results are given for the design of individual anti-HIV treatments optimizing the recovery of the immune system and minimizing side effects. In this respect, two methods are discussed. The first one combines HIV population dynamics with pharmacokinetics and pharmacodynamics models to generate drug treatments using impulsive control systems. The second one is based on optimal control theory and uses a recently published differential equation to model the side effects produced by highly active antiretroviral therapy therapies. The main advantage of these revisited methods is that the drug treatment is computed directly in amounts of drugs, which is easier to interpret by physicians and patients. PMID:25371860

  11. Plasma Mitochondrial DNA Levels as a Biomarker of Lipodystrophy Among HIV-infected Patients Treated with Highly Active Antiretroviral Therapy (HAART).

    PubMed

    Dai, Z; Cai, W; Hu, F; Lan, Y; Li, L; Chung, C; Caughey, B; Zhang, K; Tang, X

    2015-01-01

    Lipodystrophy is a common complication in HIV-infected patients taking highly active antiretroviral therapy. Its early diagnosis is crucial for timely modification of antiretroviral therapy. We hypothesize that mitochondrial DNA in plasma may be a potential marker of LD in HIV-infected individuals. In this study, we compared plasma mitochondrial DNA levels in HIV-infected individuals and non-HIV-infected individuals to investigate its potential diagnostic value. Total plasma DNA was extracted from 67 HIV-infected patients at baseline and 12, 24 and 30 months after initiating antiretroviral therapy. Real-time quantitative PCR was used to determine the mitochondrial DNA levels in plasma. Lipodystrophy was defined by the physician-assessed presence of lipoatrophy or lipohypertrophy in one or more body regions. The mitochondrial DNA levels in plasma were significantly higher at baseline in HIV-infected individuals than in non-HIV-infected individuals (p<0.05). At month 30, 33 out of 67 patients (49.2%) showed at least one sign of lipodystrophy. The mean plasma mitochondrial DNA levels in lipodystrophy patients were significantly higher compared to those without lipodystrophy at month 24 (p<0.001). The receiver operating curve analysis demonstrated that using plasma mitochondrial DNA level (with cut-off value <5.09 log10 copies/ml) as a molecular marker allowed identification of patients with lipodystrophy with a sensitivity of 64.2% and a specificity of 73.0%. Our data suggest that mitochondrial DNA levels may help to guide therapy selection with regards to HIV lipodystrophy risk.

  12. Treatment outcomes in a decentralized antiretroviral therapy program: a comparison of two levels of care in north central Nigeria.

    PubMed

    Okonkwo, Prosper; Sagay, Atiene S; Agaba, Patricia A; Yohanna, Stephen; Agbaji, Oche O; Imade, Godwin E; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A; Idoko, John A; Kanki, Phyllis J

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care. PMID:25028610

  13. Retention in Care and Outpatient Costs for Children Receiving Antiretroviral Therapy in Zambia: A Retrospective Cohort Analysis

    PubMed Central

    Scott, Callie A.; Iyer, Hari; Bwalya, Deophine Lembela; McCoy, Kelly; Meyer-Rath, Gesine; Moyo, Crispin; Bolton-Moore, Carolyn; Larson, Bruce; Rosen, Sydney

    2013-01-01

    Background There are few published estimates of the cost of pediatric antiretroviral therapy (ART) in Africa. Our objective was to estimate the outpatient cost of providing ART to children remaining in care at six public sector clinics in Zambia during the first three years after ART initiation, stratified by service delivery site and time on treatment. Methods Data on resource utilization (drugs, diagnostics, outpatient visits, fixed costs) and treatment outcomes (in care, died, lost to follow up) were extracted from medical records for 1,334 children at six sites who initiated ART at <15 years of age between 2006 and 2011. Fixed and variable unit costs (reported in 2011 USD) were estimated from the provider’s perspective using site level data. Results Median age at ART initiation was 4.0 years; median CD4 percentage was 14%. One year after ART initiation, 73% of patients remained in care, ranging from 60% to 91% depending on site. The average annual outpatient cost per patient remaining in care was $209 (95% CI, $199–$219), ranging from $116 (95% CI, $107–$126) to $516 (95% CI, $499–$533) depending on site. Average annual costs decreased as time on treatment increased. Antiretroviral drugs were the largest component of all outpatient costs (>50%) at four sites. At the two remaining sites, outpatient visits and fixed costs together accounted for >50% of outpatient costs. The distribution of costs is slightly skewed, with median costs 3% to 13% lower than average costs during the first year after ART initiation depending on site. Conclusions Outpatient costs for children initiating ART in Zambia are low and comparable to reported outpatient costs for adults. Outpatient costs and retention in care vary widely by site, suggesting opportunities for efficiency gains. Taking advantage of such opportunities will help ensure that targets for pediatric treatment coverage can be met. PMID:23840788

  14. Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda.

    PubMed

    Olds, Peter K; Kiwanuka, Julius P; Nansera, Denis; Huang, Yong; Bacchetti, Peter; Jin, Chengshi; Gandhi, Monica; Haberer, Jessica E

    2015-01-01

    Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2-10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.

  15. Treatment Outcomes in a Decentralized Antiretroviral Therapy Program: A Comparison of Two Levels of Care in North Central Nigeria

    PubMed Central

    Okonkwo, Prosper; Sagay, Atiene S.; Agaba, Patricia A.; Yohanna, Stephen; Agbaji, Oche O.; Imade, Godwin E.; Banigbe, Bolanle; Adeola, Juliet; Oyebode, Tinuade A.; Idoko, John A.; Kanki, Phyllis J.

    2014-01-01

    Background. Decentralization of antiretroviral therapy (ART) services is a key strategy to achieving universal access to treatment for people living with HIV/AIDS. Our objective was to assess clinical and laboratory outcomes within a decentralized program in Nigeria. Methods. Using a tiered hub-and-spoke model to decentralize services, a tertiary hospital scaled down services to 13 secondary-level hospitals using national and program guidelines. We obtained sociodemographic, clinical, and immunovirologic data on previously antiretroviral drug naïve patients aged ≥15 years that received HAART for at least 6 months and compared treatment outcomes between the prime and satellite sites. Results. Out of 7,747 patients, 3729 (48.1%) were enrolled at the satellites while on HAART, prime site patients achieved better immune reconstitution based on CD4+ cell counts at 12 (P < 0.001) and 24 weeks (P < 0.001) with similar responses at 48 weeks (P = 0.11) and higher rates of viral suppression (<400 c/mL) at 12 (P < 0.001) and 48 weeks (P = 0.03), but similar responses at 24 weeks (P = 0.21). Mortality was 2.3% versus 5.0% (P < 0.001) at prime and satellite sites, while transfer rate was 8.7% versus 5.5% (P = 0.001) at prime and satellites. Conclusion. ART decentralization is feasible in resource-limited settings, but efforts have to be intensified to maintain good quality of care. PMID:25028610

  16. Adherence to antiretroviral therapy among HIV and AIDS patients at the Kwa-Thema clinic in Gauteng Province, South Africa

    PubMed Central

    Eyassu, Melaku A.; Mbambo-Kekana, Nonceba P.

    2016-01-01

    Background Introduction of antiretroviral therapy (ART) has shown reduction in HIV-related mortality and morbidity in people living with HIV and AIDS. Since high levels of adherence of more than 95.0% is required to achieve effective suppression of viral load, researchers found it important to establish whether people are pursuing what is expected of them. Aim and setting The study was aimed at determining adherence to ART among HIV and AIDS patients at the Kwa-Thema clinic in Gauteng Province Methods Quantitative cross-sectional descriptive design was used. Ethical clearance was sort from MEDUNSA Research Ethics Committee. Validity and reliability were maintained throughout the study. A non-probability systematic sampling was used. Data were collected using administered structured questionnaire, and a total of 290 respondents were involved. Data were analysed using SPSS software version 22. Results The findings indicated that the adherence to ART was 77.0%. Factors that were significantly associated with adherence were gender (χ2 = 3.78, df = 1, p < 0.05), level of education (χ2 = 3.52, df = 3, p = 0.032), co-treatment of HIV and other infections (χ2 = 5.46, df = 4, p = 0.019), ability to follow ART (χ2 = 12.82, df = 1, p = 0.000 < 0.05), and types of antiretroviral drugs. Recommendation The study recommends intensification of health education campaign against stigma and gender discrimination. Providing feedback to patients regarding benefits of ART is important. Conclusion The study concluded that adherence to ART at the Kwa-Thema clinic was sub-optimal (less than 95%) at 77%, but comparable with the adherence levels in other developing countries. PMID:27380858

  17. Impact of HIV type 1 genetic subtype on the outcome of antiretroviral therapy.

    PubMed

    Atlas, Ann; Granath, Fredrik; Lindström, Anna; Lidman, Knut; Lindbäck, Stefan; Alaeus, Annette

    2005-03-01

    The objective of this study was to investigate the short-term virological outcome of antiretroviral combination therapy (ART) in relation to infection with different HIV-1 genetic subtypes. Antiretroviral drug-naive patients in Sweden were prospectively enrolled and followed for 6 months when starting ART in the period from January 1998 to January 2002. Plasma-HIV-1 RNA levels, CD4 counts, and type of ART regimen were recorded. The HIV-1 subtype was determined by direct sequencing of regions of the env or pol genes. Data from 172 patients who harbored subtypes A, B, C, D, G, and CRF01_AE were analyzed (32 A, 44 B, 34 C, 18 D, 5 G, and 19 CRF01_AE). Of all patients 84% had undetectable plasma HIV-1 RNA levels after 6 months of ART. Patients infected with CRF01_AE more often had undetectable HIV-1 RNA plasma levels than patients infected with subtypes A or D. However, the possibility that this difference is due to ethnicity cannot be ruled out. Of patients of African origin, 77% had undetectable viral load after 6 months of treatment, while the corresponding figures for Caucasians and Asians were 91% and 100%, respectively. Thus, we have found an overall good short-term virological outcome after the initiation of ART in a cohort of ARV-naive patients of diverse ethnic background infected with different HIV-1 genetic subtypes. In univariate analysis ethnicity, but not genetic subtype, correlated with virological response. However, the impact of ethnicity was moderate. Patients of African origin, who had the poorest outcome, showed a 77% virological response rate.

  18. Endosomal Trafficking of Nanoformulated Antiretroviral Therapy Facilitates Drug Particle Carriage and HIV Clearance

    PubMed Central

    Guo, Dongwei; Zhang, Gang; Wysocki, Tadeusz A.; Wysocki, Beata J.; Gelbard, Harris A.; Liu, Xin-Ming; McMillan, JoEllyn M.

    2014-01-01

    ABSTRACT Limitations of antiretroviral therapy (ART) include poor patient adherence, drug toxicities, viral resistance, and failure to penetrate viral reservoirs. Recent developments in nanoformulated ART (nanoART) could overcome such limitations. To this end, we now report a novel effect of nanoART that facilitates drug depots within intracellular compartments at or adjacent to the sites of the viral replication cycle. Poloxamer 407-coated nanocrystals containing the protease inhibitor atazanavir (ATV) were prepared by high-pressure homogenization. These drug particles readily accumulated in human monocyte-derived macrophages (MDM). NanoATV concentrations were ∼1,000 times higher in cells than those that could be achieved by the native drug. ATV particles in late and recycling endosome compartments were seen following pulldown by immunoaffinity chromatography with Rab-specific antibodies conjugated to magnetic beads. Confocal microscopy provided cross validation by immunofluorescent staining of the compartments. Mathematical modeling validated drug-endosomal interactions. Measures of reverse transcriptase activity and HIV-1 p24 levels in culture media and cells showed that such endosomal drug concentrations enhanced antiviral responses up to 1,000-fold. We conclude that late and recycling endosomes can serve as depots for nanoATV. The colocalization of nanoATV at endosomal sites of viral assembly and its slow release sped antiretroviral activities. Long-acting nanoART can serve as a drug carrier in both cells and subcellular compartments and, as such, can facilitate viral clearance. IMPORTANCE The need for long-acting ART is significant and highlighted by limitations in drug access, toxicity, adherence, and reservoir penetrance. We propose that targeting nanoformulated drugs to infected tissues, cells, and subcellular sites of viral replication may improve clinical outcomes. Endosomes are sites for human immunodeficiency virus assembly, and increasing ART

  19. Progress of the National Pediatric Free Antiretroviral Therapy program in China.

    PubMed

    Zhao, Yan; Sun, Xin; He, Yun; Tang, Zhirong; Peng, Guoping; Liu, Aiwen; Qiao, Xiaochun; Li, Huiqin; Chen, Zhiqiang; Dou, Zhihui; Ma, Ye; Liu, Zhongfu; Zhang, Fujie

    2010-10-01

    In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system.

  20. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal.

    PubMed

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-03-01

    For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver-child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver-child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information-motivation-behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child's immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment administration by

  1. CLEFT PALATE IN HIV-EXPOSED NEWBORNS OF MOTHERS ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

    PubMed Central

    James, Ayotunde; Oluwatosin, Babatunde; Njideka, Georgina; Babafemi; Benjamin, Onyekwere George; Olufemi, David; Leo, Robert; Folorunso, Isaac; Phylis; Olusina, Olusegun

    2014-01-01

    Aims Cleft lip/palate, though rare, is the commonest head and neck congenital malformation. Both genetic and environmental factors have been implicated in the aetiopathogenesis but the role of in-utero exposure to human immunodeficiency virus (HIV) and highly active antiretroviral therapy (HAART) is still being investigated. This short communication reports the occurrence of cleft palate in three newborns exposed in-utero to HIV and HAART. Material and methods This is a case series of HIV-exposed newborns observed to have cleft palate among a larger cohort of HIV-exposed and unexposed newborns in a study evaluating the effect of HIV infection and HAART on newborn hearing. The Risk Ratio (RR) was calculated to detect a potential association between in-utero exposure to Efavirenz containing ART and cleft palate. Results Three HIV-exposed newborns with cleft palate were identified during hearing screening performed on 126 HIV-exposed and 121 HIV unexposed newborns. Two had exposure to tenofovir+lamivudine+efavirenz (TDF+3TC+EFV) while the third had exposure to zidovudine+lamivudine+nevirapine (ZDV+3TC+NVP) during the first trimester. There was no statistically significant association between presence of cleft palate and exposure to an EFV containing HAART regimen (p=0.07, RR=10.95 [0.94-126.84]). Conclusions This communication highlights the possible aetiologic role of HAART in cleft palate, the need for further prospective follow-up studies and establishment of antiretroviral pregnancy, birth and neonatal registries. PMID:25653715

  2. Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)–Associated Tuberculous Meningitis

    PubMed Central

    Török, M. Estee; Yen, Nguyen Thi Bich; Chau, Tran Thi Hong; Mai, Nguyen Thi Hoang; Phu, Nguyen Hoan; Mai, Pham Phuong; Dung, Nguyen Thi; Van Vinh Chau, Nguyen; Bang, Nguyen Duc; Tien, Nguyen Anh; Minh, N. H.; Hien, Nguyen Quang; Thai, Phan Vuong Khac; Dong, Doan The; Anh, Do Thi Tuong; Thoa, Nguyen Thi Cam; Hai, Nguyen Ngoc; Lan, Nguyen Ngoc; Lan, Nguyen Thi Ngoc; Quy, Hoang Thi; Dung, Nguyen Huy; Hien, Tran Tinh; Chinh, Nguyen Tran; Simmons, Cameron Paul; de Jong, Menno; Wolbers, Marcel; Farrar, Jeremy James

    2015-01-01

    Background The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)–associated tuberculous meningitis is unknown. Methods We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81–1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87–1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration ISRCTN63659091. PMID:21596680

  3. Tuberculosis treatment and risk of stavudine substitution in first line antiretroviral therapy

    PubMed Central

    Westreich, Daniel J.; Sanne, Ian; Maskew, Mhairi; Malope-Kgokong, Babatyi; Conradie, Francesca; Majuba, Pappie; Funk, Michele Jonsson; Kaufman, Jay S.; Van Rie, Annelies; MacPhail, Patrick

    2009-01-01

    Background Treatment for tuberculosis (TB) is common among individuals receiving stavudine-containing highly active antiretroviral therapy (HAART), but the effect of TB treatment on stavudine toxicity has received little attention. We estimated the effect of TB treatment on risk of stavudine substitution among individuals receiving first-line HAART. Methods We evaluated a cohort of 7,066 patients who initiated HAART between April 2004 and March 2007 in Johannesburg, South Africa. Three exposure categories were considered: ongoing TB treatment at HAART initiation; concurrent initiation of TB treatment and HAART; incident TB treatment after HAART initiation. The outcome was single-drug stavudine substitution. Adjusted hazard ratios (aHRs) were estimated using marginal structural models to control for confounding, loss to follow-up, and competing risks. Results Individuals with ongoing and concurrent TB treatment were at increased risk of stavudine substitution, irrespective of stavudine dose. For ongoing TB treatment, aHR was 3.18 (95% confidence interval [CI] 1.82-5.56) in the first two months of HAART, 2.51 (95% CI 1.77-3.54) in months 3-6, and 1.19 (95% CI 0.94-1.52) thereafter. For concurrent TB treatment, aHR was 6.60 (95% CI 3.03-14.37) in the first two months,1.88 (95% CI 0.87-4.09) in months 3-6, and 1.07 (95% CI 0.65-1.76) thereafter. There was no effect of incident TB on stavudine substitution risk. Conclusions Risk of stavudine substitution was increased among patients receiving TB treatment, especially soon after HAART initiation. In settings where alternative antiretroviral drugs are available, initiation of stavudine in patients receiving TB treatment may need to be reconsidered. PMID:19385733

  4. Interactions of Papua New Guinea medicinal plant extracts with antiretroviral therapy

    PubMed Central

    Larson, Erica C.; Hathaway, Laura B.; Lamb, John G.; Pond, Chris D.; Rai, Prem P.; Matainaho, Teatulohi K.; Piskaut, Pius; Barrows, Louis R.; Franklin, Michael R.

    2014-01-01

    Ethnopharmacological relevance A substantial proportion of the population in Papua New Guinea (PNG) lives with human immunodeficiency virus (HIV). Treatment requires lifelong use of antiretroviral therapy (ART). The majority of people in PNG use traditional medicines (TM) derived from plants for all types of health promotions. Consequently, there is a concern that herb-drug interactions may impact the efficacy of ART. Herb-drug, or drug-drug, interactions occur at the level of metabolism through two major mechanisms: enzyme induction or enzyme inhibition. In this study, extracts of commonly-used medicinal plants from PNG were screened for herb-drug interactions related to cytochrome P450s (CYPs). Materials and Methods Sixty nine methanol extracts of TM plants were screened for their ability to induce CYPs by human aryl hydrocarbon receptor- (hAhR-) and human pregnane X receptor- (hPXR-) dependent mechanisms, utilizing a commercially available cell-based luciferase reporter system. Inhibition of three major CYPs, CYP1A2, CYP3A4, and CYP2D6, was determined using human liver microsomes and enzyme-selective model substrates. Results Almost one third of the TM plant extracts induced the hAhR-dependent expression of CYP1A2, the hPXR-dependent expression of CYP3A4, or both. Almost two thirds inhibited CYP1A2, CYP3A4, or CYP2D6, or combinations thereof. Many plant extracts exhibited both induction and inhibition properties. Conclusions We demonstrated that the potent and selective ability of extracts from PNG medicinal plants to affect drug metabolizing enzymes through induction and/or inhibition is a common phenomenon. Use of traditional medicines concomitantly with ART could dramatically alter the concentrations of antiretroviral drugs in the body; and their efficacy. PNG healthcare providers should counsel HIV patients because of this consequence. PMID:25138353

  5. Progress of the National Pediatric Free Antiretroviral Therapy program in China.

    PubMed

    Zhao, Yan; Sun, Xin; He, Yun; Tang, Zhirong; Peng, Guoping; Liu, Aiwen; Qiao, Xiaochun; Li, Huiqin; Chen, Zhiqiang; Dou, Zhihui; Ma, Ye; Liu, Zhongfu; Zhang, Fujie

    2010-10-01

    In 2003, the Chinese Government initiated a free antiretroviral therapy (ART) program focusing on adult AIDS patients. Pediatric antiretroviral (ARV) formulations were yet unavailable. It was not until July 2005, with the initiation of a two-stage program implemented by the Chinese Ministry of Health, that pediatric formulations became accessible in China. Initially, the pediatric ART program was piloted in six provinces with the highest incidences of pediatric HIV/AIDS. The pilot stage allowed the Chinese Center for Disease Control and Prevention (CCDC) to finalize entry criteria, treatment regimen, and patient monitoring and follow-up procedures. The second stage commenced at the end of 2006 when the program was scaled-up nationally. In order to guarantee treatment of pediatric patients, extensive training in the selection of appropriate ARV drug regimen and dosage was provided to doctors, often through on-site collaboration with domestic and international experts. The CCDC simultaneously established a pediatric ARV management system and a pediatric ART information system. CD4 count and other laboratory tests are being routinely performed on these pediatric patients. By the end of June 2009, 1529 pediatric patients had received ARV under the national program. However, challenges remain. Firstly, many children infected with HIV/AIDS live in rural areas where the treatment quality is hindered by the limited number of medical facilities and skilled medical workers. Secondly, much of the pediatric ARV drug supply depends on donation. An effort needs to be made by the Chinese Government to establish China's own drug procurement and supply system. PMID:20665285

  6. Barriers to acceptance and adherence of antiretroviral therapy in urban Zambian women: a qualitative study

    PubMed Central

    Murray, Laura K.; Semrau, Katherine; McCurley, Ellen; Thea, Donald M.; Scott, Nancy; Mwiya, Mwiya; Kankasa, Chipepo; Bass, Judith; Bolton, Paul

    2009-01-01

    Sub-Saharan Africa contains over 60% of the world’s HIV infections and Zambia is among the most severely affected countries in the region. As antiretroviral programs have been rapidly expanding, the long-term success of these programs depends on a good understanding of the behavioral determinants of acceptance and adherence to antiretroviral therapy (ART). The study used qualitative methods to gain local insight into potentially important factors affecting HIV-infected women’s decision to accept or continue with ART. Some of the barriers identified by this study are consistent with factors cited in the existing adherence literature from both developed and developing nations such as side effects, hunger and stigma; other factors have not been previously reported. One major theme was unfamiliarity with the implications of having a chronic, potentially deadly disease. Other emerging themes from this study include the complicated effect of ART on interpersonal relationship, particularly between husbands and wives, the presence of depression and hopelessness, and lack of accurate information. The results suggest that the reasons for non-uptake of treatment include issues related to local cultural frameworks (e.g., illness ideology), mental and behavioral health (e.g., depression and/or interpersonal challenges), stigma, and motivating factors (e.g., values of church or marriage) of different cultures that affect the ability and willingness to take life-saving medicine for a long period of time. Qualitative studies are critical to better understand why ART eligible individuals are choosing not to initiate or continue treatment to achieve needed adherence levels. PMID:19085223

  7. Video observations of treatment administration to children on antiretroviral therapy in rural KwaZulu-Natal

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-01-01

    ABSTRACT For children younger than five years, caregivers are responsible for the measurement and administration of antiretroviral medication doses to children. Failure to adhere to the regimen as prescribed may lead to high viral loads (VLs), immune suppression and ultimately drug resistance. In the content of this study, adherence refers to adequate dosing of the medication by a caregiver. Acquired drug resistance to antiretroviral therapy (ART) is prevalent amongst children in South Africa, and poor adherence to the dosing regimen by caregivers may be associated with this problem. In this qualitative study, we purposively recruited 33 caregiver–child dyads from the Hlabisa HIV Treatment and Care Programme database. Children were divided into three groups based on their VL at the time of recruitment. Children with a VL ≥ 400 cps/ml were grouped as unsuppressed (n = 11); children with a VL ≤ 400 cps/ml were grouped as suppressed (n = 12); and children with no VL data were grouped as newly initiated (n = 10). Caregiver–child dyads were visited at their households twice to document, by means of video recording, how treatment was administered to the child. Observational notes and video recordings were entered into ATLAS.ti v 7 and analysed thematically. Results were interpreted through the lens of Ecological Systems Theory and the information–motivation–behavioural skills model was used to understand and reflect on several of the factors influencing adherence within the child’s immediate environment as identified in this study. Thematic video analysis indicated context- and medication-related factors influencing ART adherence. Although the majority of children in this sample took their medicine successfully, caregivers experienced several challenges with the preparation and administration of the medications. In the context of emerging drug resistance, efforts are needed to carefully monitor caregiver knowledge of treatment

  8. Socioeconomic status and survival of persons with AIDS before and after the introduction of highly active antiretroviral therapy. Lazio AIDS Surveillance Collaborative Group.

    PubMed

    Rapiti, E; Porta, D; Forastiere, F; Fusco, D; Perucci, C A

    2000-09-01

    We estimated the AIDS survival by neighborhood socioeconomic status before (1993-1995) and after (1996-1997) the introduction of highly active antiretroviral therapy in Rome, Italy, in a retrospective cohort of persons with AIDS followed through July 31, 1998. Participants included 1,474 persons with AIDS residing in Rome who were diagnosed in 1993-1997. We calculated hazard ratios (HRs) of death for two diagnostic periods (before and after highly active antiretroviral therapy was introduced) by neighborhood socioeconomic status categorized into four levels (level I = highest socioeconomic status), using the Cox model and adjusting for gender, age, intravenous drug use, CD4 cell count at diagnosis, AIDS-defining disease, and hospital of diagnosis. Thirty-four per cent of persons with AIDS (N = 503) had survived as of mid-1998. For persons with AIDS diagnosed in 1993-1995, we found little difference in the risk of death by neighborhood socioeconomic status. For 1996-1997, the risk of death was greater for persons with lower neighborhood socioeconomic status, especially for levels III and IV [HR = 2.81 (95% confidence interval = 1.38-5.76), and HR = 2.55 (95% confidence interval = 1.27-5.14), respectively, compared with level I]. Stratified analyses showed that the greatest difference was found for women and drug users. In conclusion, even in a country with universal health coverage that provides therapy at no cost, differences in survival of persons with AIDS have emerged by neighborhood socioeconomic status since highly active antiretroviral therapy was introduced. Inequalities in health-care access or in medical management, or poor adherence to treatment, could explain the observed heterogeneity.

  9. Disease-modifying therapeutic concepts for HIV in the era of highly active antiretroviral therapy.

    PubMed

    Butler, Scott L; Valdez, Hernan; Westby, Michael; Perros, Manos; June, Carl H; Jacobson, Jeffrey M; Levy, Yves; Cooper, David A; Douek, Daniel; Lederman, Michael M; Tebas, Pablo

    2011-11-01

    Chronic HIV infection is associated with persistent immune activation and inflammation even among patients virologically suppressed on antiretroviral therapy for years. Chronic immune activation has been associated with poor outcomes--both AIDS-defining and non-AIDS-defining clinical events--and persistent CD4 T-cell depletion. The cause of chronic immune activation in well-controlled HIV infection is unknown. Proposed drivers include residual viral replication, microbial translocation, and coinfecting pathogens. Therapeutic interventions targeting immune activation are emerging, from approaches that interfere directly with activation and inflammatory pathways to those that prevent microbial translocation or decrease the availability of host target cells for the virus. In the context of the disappointing results of the interleukin-2 trials, the main challenges to developing these disease-modifying therapies include identifying an adequate target population and choosing surrogate endpoints that will provide positive proof-of-concept that the interventions will translate into long-term clinical benefit before embarking on large clinical endpoint trials. PMID:21792065

  10. Disseminated rhodococcus equi infection in HIV infection despite highly active antiretroviral therapy

    PubMed Central

    2011-01-01

    Background Rhodococcus equi (R.equi) is an acid fast, GRAM + coccobacillus, which is widespread in the soil and causes pulmonary and extrapulmonary infections in immunocompromised people. In the context of HIV infection, R.equi infection (rhodococcosis) is regarded as an opportunistic disease, and its outcome is influenced by highly active antiretroviral therapy (HAART). Case presentation We report two cases of HIV-related rhodococcosis that disseminated despite suppressive HAART and anti-rhodococcal treatment; in both cases there was no immunological recovery, with CD4+ cells count below 200/μL. In the first case, pulmonary rhodococcosis presented 6 months after initiation of HAART, and was followed by an extracerebral intracranial and a cerebral rhodococcal abscess 1 and 8 months, respectively, after onset of pulmonary infection. The second case was characterized by a protracted course with spread of infection to various organs, including subcutaneous tissue, skin, colon and other intra-abdominal tissues, and central nervous system; the spread started 4 years after clinical resolution of a first pulmonary manifestation and progressed over a period of 2 years. Conclusions Our report highlights the importance of an effective immune recovery, despite fully suppressive HAART, along with anti-rhodococcal therapy, in order to clear rhodococcal infection. PMID:22168333

  11. Highly active antiretroviral therapy potently suppresses HIV infection in humanized Rag2-/-gammac-/- mice.

    PubMed

    Sango, Kaori; Joseph, Aviva; Patel, Mahesh; Osiecki, Kristin; Dutta, Monica; Goldstein, Harris

    2010-07-01

    Humanized Rag2(-/-)gamma(c)(-/-) mice (Hu-DKO mice) become populated with functional human T cells, B cells, and dendritic cells following transplantation with human hematopoietic stem cells (HSC) and represent an improved model for studying HIV infection in vivo. In the current study we demonstrated that intrasplenic inoculation of hu-DKO mice with HIV-1 initiated a higher level of HIV infection than intravenous or intraperitoneal inoculation, associated with a reciprocal decrease in peripheral CD4(+) T cells and increase in peripheral CD8(+) T cells. HIV infection by intrasplenic injection increased serum levels of human IgG and IgM including human IgM and IgG specific for HIV-1 gp120. There was a significant inverse correlation between the level of HIV-1 infection and the extent of CD4(+) T cell depletion. Highly active antiretroviral therapy (HAART) initiated 1 week after HIV-1 inoculation markedly suppressed HIV-1 infection and prevented CD4(+) T cell depletion. Taken together, these findings demonstrate that intrasplenic injection of hu-DKO mice with HIV is a more efficient route of HIV infection than intravenous or intraperitoneal injection and generates increased infection associated with an increased anti-HIV humoral response. This animal model can serve as a valuable in vivo model to study the efficacy of anti-HIV therapies.

  12. Human Immunodeficiency Virus-Associated Diarrhea: Still an Issue in the Era of Antiretroviral Therapy.

    PubMed

    Dikman, Andrew E; Schonfeld, Emily; Srisarajivakul, Nalinee C; Poles, Michael A

    2015-08-01

    Over half of patients with human immunodeficiency virus (HIV) experience diarrhea that contributes negatively to quality of life and adherence to antiretroviral therapy (ART). Opportunistic infectious agents that cause diarrhea in patients with HIV span the array of protozoa, fungi, viruses, and bacteria. With global use of ART, the incidence of diarrhea because of opportunistic infections has decreased; however, the incidence of noninfectious diarrhea has increased. The etiology of noninfectious diarrhea in patients with HIV is multifactorial and includes ART-associated diarrhea and gastrointestinal damage related to HIV infection (i.e., HIV enteropathy). A basic algorithm for the diagnosis of diarrhea in patients with HIV includes physical examination, a review of medical history, assessment of HIV viral load and CD4+ T cell count, stool microbiologic assessment, and endoscopic evaluation, if needed. For patients with negative diagnostic results, the diagnosis of noninfectious diarrhea may be considered. Pharmacologic options for the treatment of noninfectious diarrhea are primarily supportive; however, the use of many unapproved agents is based on unstudied and anecdotal information. In addition, these agents can be associated with treatment-limiting adverse events (AEs), such as drug-drug interactions with ART regimens, abuse liability, and additional gastrointestinal AEs. Currently, crofelemer, an antisecretory agent, is the only therapy approved in the USA for the symptomatic relief of noninfectious diarrhea in patients with HIV on ART. PMID:25772777

  13. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

    PubMed Central

    Siedner, Mark J.

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  14. START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection.

    PubMed

    Siedner, Mark J

    2016-01-01

    The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed. PMID:26989755

  15. The long-term benefits of genotypic resistance testing in patients with extensive prior antiretroviral therapy: a model-based approach

    PubMed Central

    Yazdanpanah, Y; Vray, M; Meynard, J; Losina, E; Weinstein, MC; Morand-Joubert, L; Goldie, SJ; Hsu, HE; Walensky, RP; Dalban, C; Sax, PE; Girard, PM; Freedberg, KA

    2008-01-01

    Objectives Resistance testing in HIV disease may provide long-term benefits that are not evident from short-term data. Our objectives were to estimate the long-term effectiveness, cost and cost-effectiveness of genotype testing in patients with extensive antiretroviral exposure. Methods We used an HIV simulation model to estimate the long-term effectiveness and cost-effectiveness of genotype testing. Clinical data incorporated into the model were from NARVAL, a randomized trial of resistance testing in patients with extensive antiretroviral exposure, and other randomized trials. Each simulated patient was eligible for up to three sequential regimens of antiretroviral therapy (i.e. two additional regimens beyond the trial-based regimen) using drugs not available at the time of the study, such as lopinavir/ritonavir, darunavir/ritonavir and enfuvirtide. Results In the long term, projected undiscounted life expectancy increased from 132.2 months with clinical judgement alone to 147.9 months with genotype testing. Median survival was estimated at 11.9 years in the resistance testing arm vs 10.4 years in the clinical judgement alone arm. Because of increased survival, the projected lifetime discounted cost of genotype testing was greater than for clinical judgement alone (€313 900 vs €263100; US$399 000 vs US$334 400). Genotype testing cost €69 600 (US$88 500) per quality-adjusted life year gained compared with clinical judgement alone. Conclusions In patients with extensive prior antiretroviral exposure, genotype testing is likely to increase life expectancy in the long term as a result of the increased likelihood of receiving two active new drugs. Genotype testing is associated with cost-effectiveness comparable to that of strategies accepted in patients with advanced HIV disease, such as enfuvirtide use. PMID:17760736

  16. Impact of a decade of successful antiretroviral therapy initiated at HIV-1 seroconversion on blood and rectal reservoirs

    PubMed Central

    Malatinkova, Eva; Spiegelaere, Ward De; Bonczkowski, Pawel; Kiselinova, Maja; Vervisch, Karen; Trypsteen, Wim; Johnson, Margaret; Verhofstede, Chris; de Looze, Danny; Murray, Charles; Loes, Sabine Kinloch-de; Vandekerckhove, Linos

    2015-01-01

    Persistent reservoirs remain the major obstacles to achieve an HIV-1 cure. Prolonged early antiretroviral therapy (ART) may reduce the extent of reservoirs and allow for virological control after ART discontinuation. We compared HIV-1 reservoirs in a cross-sectional study using polymerase chain reaction-based techniques in blood and tissue of early-treated seroconverters, late-treated patients, ART-naïve seroconverters, and long-term non-progressors (LTNPs) who have spontaneous virological control without treatment. A decade of early ART reduced the total and integrated HIV-1 DNA levels compared with later treatment initiation, but not reaching the low levels found in LTNPs. Total HIV-1 DNA in rectal biopsies did not differ between cohorts. Importantly, lower viral transcription (HIV-1 unspliced RNA) and enhanced immune preservation (CD4/CD8), reminiscent of LTNPs, were found in early compared to late-treated patients. This suggests that early treatment is associated with some immunovirological features of LTNPs that may improve the outcome of future interventions aimed at a functional cure. DOI: http://dx.doi.org/10.7554/eLife.09115.001 PMID:26439007

  17. Comparative Effectiveness of First Antiretroviral Regimens in Clinical Practice Using a Causal Approach.

    PubMed

    Cuzin, Lise; Pugliese, Pascal; Allavena, Clotilde; Katlama, Christine; Cotte, Laurent; Cheret, Antoine; Cabié, André; Rey, David; Chirouze, Catherine; Bani-Sadr, Firouze; Flandre, Philippe

    2015-09-01

    The objective of this study was to estimate the cumulative incidences of failure by months 12 (M12) and 24 (M24) for the most prescribed first-line anti-retroviral regimens (ART). It is retrospective analysis of a prospectively collected database. All patients who initiated their first ART with the most prescribed regimens between 1st January 2004 and 30th June 2013 in 12 large HIV reference centers in France were included. The outcome was treatment failure--defined by any treatment modification for virological or tolerability reasons--and comparisons between regimens were carried out at M12 and M24. Adjusted and weighted methods via the propensity score (PS) were used to compare the effectiveness of the first antiretroviral regimens. Potential confounders of the treatment-outcome association were used to estimate PS with multinomial logistic regression. Overall, 3128 and 2690 patients were included in the M12 and M24 analyses, respectively. Patients received 5 different regimens (ABC/3TC with ATV/r or DRV/r, TDF/FTC with ATV/r, DRV/r, or EFV). Failure was reported in 25% and 42% at M12 and M24, respectively. Patients who received TDF/FTC/EFV had a significantly higher proportion of failure at M12 by comparison with TDF/FTC with DRV/r (reference), but not at M24. Patients in the 3 other groups had a trend toward a higher proportion of failure at M12 although not statistically significant. No difference was found at M24. Using data from a large prospective cohort, we found that boosted atazanavir and darunavir had comparable effectiveness, whatever the associated NRTIs, whereas efavirenz-based regimens were relatively less performing on the short term.

  18. High frequency of antiretroviral drug resistance among HIV-infected adults receiving first-line highly active antiretroviral therapy in N'Djamena, Chad.

    PubMed

    Koyalta, Donato; Charpentier, Charlotte; Beassamda, Jatibi; Rey, Elisabeth; Si-Mohamed, Ali; Djemadji-Oudjeil, Noël; Bélec, Laurent

    2009-07-01

    Antiretroviral drug resistance was evaluated in 88 adults infected with human immunodeficiency virus, most with subtype CRF11_cpx, who had received a first-line antiretroviral regimen for 6 months, in N'Djamena, Chad. A total of 47 patients (53%) had detectable viral load at month 6, and 56 (64%) had at least 1 antiretroviral resistance mutation observed.

  19. Unanticipated Effects of New Drug Availability on Antiretroviral Durability: Implications for Comparative Effectiveness Research

    PubMed Central

    Eaton, Ellen F.; Tamhane, Ashutosh R.; Burkholder, Greer A.; Willig, James H.; Saag, Michael S.; Mugavero, Michael J.

    2016-01-01

    Background. Durability of antiretroviral (ARV) therapy is associated with improved human immunodeficiency virus (HIV) outcomes. Data on ARV regimen durability in recent years and clinical settings are lacking. Methods. This retrospective follow-up study included treatment-naive HIV-infected patients initiating ARV therapy between January 2007 and December 2012 in a university-affiliated HIV clinic in the Southeastern United States. Outcome of interest was durability (time to discontinuation) of the initial regimen. Durability was evaluated using Kaplan-Meier survival analyses. Cox proportional hazard analyses was used to evaluate the association among durability and sociodemographic, clinical, and regimen-level factors. Results. Overall, 546 patients were analyzed. Median durability of all regimens was 39.5 months (95% confidence interval, 34.1–44.4). Commonly prescribed regimens were emtricitabine and tenofovir with efavirenz (51%; median duration = 40.1 months) and with raltegravir (14%; 47.8 months). Overall, 67% of patients had an undetectable viral load at the time of regimen cessation. Discontinuation was less likely with an integrase strand transfer inhibitor (adjusted hazards ratio [aHR] = 0.35, P = .001) or protease inhibitor-based regimen (aHR = 0.45, P = .006) and more likely with a higher pill burden (aHR = 2.25, P = .003) and a later treatment era (aHR = 1.64, P < .001). Conclusions. Initial ARV regimen longevity declined in recent years contemporaneous with the availability of several new ARV drugs and combinations. Reduced durability mostly results from a preference for newly approved regimens rather than indicating failing therapy, as indicated by viral suppression observed in a majority of patients (67%) prior to regimen cessation. Durability is influenced by extrinsic factors including new drug availability and provider preference. Medication durability must be interpreted carefully in the context of a dynamic treatment landscape. PMID

  20. Origin of Rebound Plasma HIV Includes Cells with Identical Proviruses That Are Transcriptionally Active before Stopping of Antiretroviral Therapy

    PubMed Central

    Wiegand, Ann; Shao, Wei; Coffin, John M.; Mellors, John W.; Lederman, Michael; Gandhi, Rajesh T.; Keele, Brandon F.

    2015-01-01

    ABSTRACT Understanding the origin of HIV variants during viral rebound may provide insight into the composition of the HIV reservoir and has implications for the design of curative interventions. HIV single-genome sequences were obtained from 10 AIDS Clinical Trials Group participants who underwent analytic antiretroviral therapy (ART) interruption (ATI). Rebounding variants were compared with those in pre-ART plasma in all 10 participants and with on-ART peripheral blood mononuclear cell (PBMC)-associated DNA and RNA (CA-RNA) in 7/10 participants. The highest viral diversities were found in the DNA and CA-RNA populations. In 3 of 7 participants, we detected multiple, identical DNA and CA-RNA sequences during suppression on ART that exactly matched plasma HIV sequences. Hypermutated DNA and CA-RNA were detected in four participants, contributing to diversities in these compartments that were higher than in the pre-ART and post-ATI plasma. Shifts in the viral rebound populations could be detected in some participants over the 2- to 3-month observation period. These findings suggest that a source of initial rebound viremia could be populations of infected cells that clonally expanded prior to and/or during ART, some of which were already expressing HIV RNA before treatment was interrupted. These clonally expanding populations of HIV-infected cells may represent an important target for strategies aimed at achieving reservoir reduction and sustained virologic remission. IMPORTANCE Antiretroviral therapy alone cannot eradicate the HIV reservoir, and viral rebound is generally rapid after treatment interruption. It has been suggested that clonal expansion of HIV-infected cells is an important mechanism of HIV reservoir persistence, but the contribution of these clonally proliferating cells to the rebounding virus is unknown. We report a study of AIDS Clinical Trials Group participants who underwent treatment interruption and compared rebounding plasma virus with that

  1. A method to manage and share anti-retroviral (ARV) therapy information of human immunodeficiency virus (HIV) patients in Vietnam.

    PubMed

    Nguyen, Phung Anh; Syed-Abdul, Shabbir; Minamareddy, Priti; Lee, Peisan; Ngo, Thuy Dieu; Iqbal, Usman; Nguyen, Phuong Hoang; Jian, Wen-Shan; Li, Yu-Chuan Jack

    2013-08-01

    Management of antiretroviral (ARV) drug and HIV patients data is an important component of Vietnam Administration of HIV/AIDS Control (VAAC) Department and hospitals/health care units when people often travel in other places of Vietnam; therefore, it would lead to a number of medical errors in treatment as well as patients do not adhere to ARV therapy. In this paper, we describe a system that manages and shares antiretroviral therapy information of 4438 HIV patients in three healthcare centers in Hanoi capital of Vietnam. The overall design considerations, architecture and the integration of centralized database and decentralized management for the system are also presented. The findings from this study can serve as a guide to consider in the implementation model of health care to manage and share information of patients not only in HIV infection, but also in the other chronic and non-communicable diseases.

  2. Cellular automata approach for the dynamics of HIV infection under antiretroviral therapies: The role of the virus diffusion

    NASA Astrophysics Data System (ADS)

    González, Ramón E. R.; de Figueirêdo, Pedro Hugo; Coutinho, Sérgio

    2013-10-01

    We study a cellular automata model to test the timing of antiretroviral therapy strategies for the dynamics of infection with human immunodeficiency virus (HIV). We focus on the role of virus diffusion when its population is included in previous cellular automata model that describes the dynamics of the lymphocytes cells population during infection. This inclusion allows us to consider the spread of infection by the virus-cell interaction, beyond that which occurs by cell-cell contagion. The results show an acceleration of the infectious process in the absence of treatment, but show better efficiency in reducing the risk of the onset of AIDS when combined antiretroviral therapies are used even with drugs of low effectiveness. Comparison of results with clinical data supports the conclusions of this study.

  3. Spectrum of imaging appearances of intracranial cryptococcal infection in HIV/AIDS patients in the anti-retroviral therapy era.

    PubMed

    Offiah, Curtis E; Naseer, Aisha

    2016-01-01

    Cryptococcus neoformans infection is the most common fungal infection of the central nervous system (CNS) in advanced human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, but remains a relatively uncommon CNS infection in both the immunocompromised and immunocompetent patient population, rendering it a somewhat elusive and frequently overlooked diagnosis. The morbidity and mortality associated with CNS cryptococcal infection can be significantly reduced by early recognition of the imaging appearances by the radiologist in order to focus and expedite clinical management and treatment. The emergence and evolution of anti-retroviral therapy have also impacted significantly on the imaging appearances, morbidity, and mortality of this neuro-infection. The constellation of varied imaging appearances associated with cryptococcal CNS infection in the HIV and AIDS population in the era of highly active anti-retroviral therapy (HAART) will be presented in this review. PMID:26564776

  4. Predicting Malawian Women’s Intention to Adhere to Antiretroviral Therapy

    PubMed Central

    McKinney, Ogbochi; Modeste, Naomi N.; Lee, Jerry W.; Gleason, Peter C.

    2015-01-01

    Background With the increase in scaling up of antiretroviral therapy (ART), knowledge of the need for adherence to ART is pivotal for successful treatment outcomes. Design and Methods A cross-sectional study was carried out between October and December 2013. We administered theory of planned behaviour (TPB) and adherence questionnaires to 358 women aged 18-49 years, from a rural and urban ART-clinics in southern Malawi. Hierarchical linear regression models were used to predict intentions to adhere to ART. Results Regression models show that attitude (β=0.47), subjective norm (β=0.31) and perceived behavioural control (β=0.12) explain 55% of the variance in intentions to adhere to ART. The relationship between both food insecurity and perceived side effects with intentions to adhere to ART is mediated by attitude, subjective norm, and perceived behavioural control. Household (r=0.20) and individual (r=0.21) food insecurity were positively and significantly correlated with perceived behavioural control. Household food insecurity had a negative correlation with perceived side effects (r=-0.11). Perceived side effects were positively correlated with attitude (r=0.25). There was no statistically significant relationship between intentions to adhere to ART in the future and one month self-report of past month adherence. These interactions suggest that attitude predicted adherence only when food insecurity is high or perception of side effects is strong. Conclusions This study shows that modification might be needed when using TPB constructs in resource constraint environments. Significance for public health The knowledge of the rates of adherence to antiretroviral therapy (ART) could be used to evaluate planning and project, which could lead to better outcomes predicted by treatment efficacy data. In addition, knowledge of adherence behaviour could help the development of interventions focusing on collaboration between healthcare providers and Malawian government to

  5. Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

    PubMed

    Pérez, Lissette; Kourí, Vivian; Alemán, Yoan; Abrahantes, Yeisel; Correa, Consuelo; Aragonés, Carlos; Martínez, Orlando; Pérez, Jorge; Fonseca, Carlos; Campos, Jorge; Álvarez, Delmis; Schrooten, Yoeri; Dekeersmaeker, Nathalie; Imbrechts, Stijn; Beheydt, Gertjan; Vinken, Lore; Soto, Yudira; Álvarez, Alina; Vandamme, Anne-Mieke; Van Laethem, Kristel

    2013-06-01

    In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the

  6. Expression of oral cytokines in HIV-infected subjects with long-term use of antiretroviral therapy

    PubMed Central

    Nittayananta, Wipawee; Amornthatree, Korntip; Kemapunmanus, Marisa; Talungchit, Sineepat; Sriplung, Hutcha

    2013-01-01

    Objectives The objectives of this study were to determine 1) the expression of oral pro-inflammatory cytokines in HIV-infected subjects compared with non-HIV individuals, 2) the cytokine expression in the subjects with antiretroviral therapy (ART) compared with those without ART, and 3) factors associated with the expression of the cytokines. Materials and methods Oral examination was performed and saliva samples were collected and analyzed for the expression of pro-inflammatory cytokines using ELISA. Logistic regression analysis was performed to determine the association between HIV/ART status and the cytokine expression. Results One hundred and fifty-seven HIV-infected subjects with and without ART, and 50 non-HIV individuals were enrolled. TNF-α and IL-6 in saliva were significantly decreased, while IL-8 was significantly increased in HIV infection (p< 0.05). Changes in the expression of IL-8 was also observed between HIV-infected subjects who were and were not on ART (p< 0.05). Duration of HIV infection and smoking were significantly associated with the expression of pro-inflammatory cytokines in saliva (p< 0.05). Conclusion Oral innate immunity is affected by HIV infection and use of ART. IL-8 may be the useful biomarker to identify subjects at risk of infection and malignant transformation due to HIV infection and long-term use of ART. PMID:23718561

  7. Abnormalities in body composition and nutritional status in HIV-infected children and adolescents on antiretroviral therapy.

    PubMed

    Ramalho, L C de Barros; Gonçalves, E M; de Carvalho, W R G; Guerra-Junior, G; Centeville, M; Aoki, F H; Morcillo, A M; dos Santos Vilela, M M; da Silva, M T N

    2011-08-01

    This cross-sectional study aimed to compare growth, nutritional status and body composition outcomes between a group of 94 HIV-infected children and adolescents on antiretroviral therapy (ART) and 364 healthy controls, and to evaluate their association with clinical and lifestyle variables within the HIV-infected group. When compared with the control group, HIV patients had higher risk of stunting (odds ratio [OR] 5.33, 95% confidence interval [CI]: 2.83-10.04) and thinness (OR 4.7, 95% CI: 2.44-9.06), higher waist-to-hip ratios (medians 0.89 versus 0.82 for boys and 0.90 versus 0.77 for girls, P < 0.001), and lower prevalence of overweight or obesity (OR 0.33, 95% CI: 0.14-0.78). Protease inhibitor usage was associated with thinness (OR 3.51, 95% CI 1.07-11.44) and lipoatrophy (OR 3.5, 95% CI 1.37-8.95). HIV-infected children on ART showed significant nutritional status and body composition abnormalities, consistent with the severity of vertical HIV infection and the consequences of prolonged ART.

  8. Current strategies for improving access and adherence to antiretroviral therapies in resource-limited settings

    PubMed Central

    Scanlon, Michael L; Vreeman, Rachel C

    2013-01-01

    The rollout of antiretroviral therapy (ART) significantly reduced human immunodeficiency virus (HIV)-related morbidity and mortality, but good clinical outcomes depend on access and adherence to treatment. In resource-limited settings, where over 90% of the world’s HIV-infected population resides, data on barriers to treatment are emerging that contribute to low rates of uptake in HIV testing, linkage to and retention in HIV care systems, and suboptimal adherence rates to therapy. A review of the literature reveals limited evidence to inform strategies to improve access and adherence with the majority of studies from sub-Saharan Africa. Data from observational studies and randomized controlled trials support home-based, mobile and antenatal care HIV testing, task-shifting from doctor-based to nurse-based and lower level provider care, and adherence support through education, counseling and mobile phone messaging services. Strategies with more limited evidence include targeted HIV testing for couples and family members of ART patients, decentralization of HIV care, including through home- and community-based ART programs, and adherence promotion through peer health workers, treatment supporters, and directly observed therapy. There is little evidence for improving access and adherence among vulnerable groups such as women, children and adolescents, and other high-risk populations and for addressing major barriers. Overall, studies are few in number and suffer from methodological issues. Recommendations for further research include health information technology, social-level factors like HIV stigma, and new research directions in cost-effectiveness, operations, and implementation. Findings from this review make a compelling case for more data to guide strategies to improve access and adherence to treatment in resource-limited settings. PMID:23326204

  9. Opportunistic diseases in HIV-infected patients in Gabon following the administration of highly active antiretroviral therapy: a retrospective study.

    PubMed

    Okome-Nkoumou, Madeleine; Guiyedi, Vincent; Ondounda, Magloire; Efire, Nora; Clevenbergh, Philippe; Dibo, Mireille; Dzeing-Ella, Arnaud

    2014-02-01

    Opportunistic diseases cause substantial morbidity and mortality to human immunodeficiency virus (HIV)-infected patients. Highly active antiretroviral therapy (HAART) leading to immune reconstitution is the most effective treatment of preventing opportunistic diseases. This retrospective study established an epidemiologic profile of opportunistic diseases 10 years after the introduction of HAART. The HIV antiretroviral therapy-naive patients matching inclusion criteria were included. The primary outcome was the prevalence of opportunistic diseases. From January 1, 2002 to September 30, 2010, 654 opportunistic diseases were identified in 458 patients. Pulmonary tuberculosis, herpes zoster, cerebral toxoplasmosis, oral candidiasis, and severe pneumonia accounted for 22.05%, 15.94%, 14.19%, 14.19%, and 9.39%, respectively. Cryptococcal meningitis and pneumocystosis accounted for 0.44% and 0.21%, respectively. The prevalence of opportunistic diseases in Gabon remains high. New guidelines emphasize the importance of initiating antiretroviral therapy early to reconstitute the immune system, and reduce disease risk, and treat the primary opportunistic infection of pulmonary tuberculosis.

  10. Imported Acquired Immunodeficiency Syndrome–Related Histoplasmosis in Metropolitan France: A Comparison of Pre–Highly Active Anti-Retroviral Therapy and Highly Active Anti-Retroviral Therapy Eras

    PubMed Central

    Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

    2011-01-01

    Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome–related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985–1994) and HAART (1997–2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome–related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era. PMID:22049053

  11. Imported acquired immunodeficiency syndrome-related histoplasmosis in metropolitan France: a comparison of pre-highly active anti-retroviral therapy and highly active anti-retroviral therapy eras.

    PubMed

    Peigne, Vincent; Dromer, Françoise; Elie, Caroline; Lidove, Olivier; Lortholary, Olivier

    2011-11-01

    Histoplasma capsulatum var. capsulatum infection is rare outside disease-endemic areas. Clinical presentation and outcome of acquired immunodeficiency syndrome-related histoplasmosis are unknown in non-endemic areas with wide access to highly active anti-retroviral therapy (HAART). Retrospective analysis of cases recorded at the French National Reference Center for Mycoses and Antifungals during two decades: pre-HAART (1985-1994) and HAART (1997-2006). Clinical features and outcome of all adults with proven acquired immunodeficiency syndrome-related histoplasmosis were compared between the two periods. One hundred four patients were included (40 during the pre-HAART era and 64 during the HAART era). Diagnosis was established a mean of 62 days after onset of symptoms. One-year overall mortality rates decreased from 53% (pre-HAART era) to 22% (HAART era). Diagnosis during the pre-HAART era and an older age were the only independent factors associated with death. Histoplasmosis is a rare invasive fungal infection outside disease-endemic areas. Its prognosis improved significantly during the HAART era.

  12. Knowledge, Stigma, and Behavioral Outcomes among Antiretroviral Therapy Patients Exposed to Nalamdana's Radio and Theater Program in Tamil Nadu, India

    ERIC Educational Resources Information Center

    Nambiar, Devaki; Ramakrishnan, Vimala; Kumar, Paresh; Varma, Rajeev; Balaji, Nithya; Rajendran, Jeeva; Jhona, Loretta; Chandrasekar, Chokkalingam; Gere, David

    2011-01-01

    Arts-based programs have improved HIV-related knowledge, attitudes, and behavior in general and at-risk populations. With HIV transformed into a chronic condition, this study compares patients at consecutive stages of receiving antiretroviral treatment, coinciding with exposure to a radio-and-theater-based educational program (unexposed [N = 120],…

  13. Adult combination antiretroviral therapy in sub-Saharan Africa: lessons from Botswana and future challenges

    PubMed Central

    Wester, C William; Bussmann, Hermann; Koethe, John; Moffat, Claire; Vermund, Sten; Essex, Max; Marlink, Richard G

    2009-01-01

    Numerous national public initiatives offering first-line combination antiretroviral therapy (cART) for HIV infection have commenced in sub-Saharan Africa since 2002. Presently, 2.1 million of an estimated seven million Africans in need of cART are receiving treatment. Analyses from the region report favorable clinical/treatment outcomes and impressive declines in AIDS-related mortality among HIV-1-infected adults and children receiving cART. While immunologic recovery, virologic suppression and cART adherence rates are on par with resource-rich settings, loss to follow-up and high mortality rates, especially within the first 6 months of treatment, remain a significant problem. Over the next decade, cART coverage rates are expected to improve across the region, with attendant increases in healthcare utilization for HIV- and non-HIV-related complications and the need for expanded laboratory and clinical services. Planned and in-progress trials will evaluate the use of cART to prevent primary HIV-1 infection with so-called ‘test and treat’ expansions of coverage and treatment. Education and training programs as well as patient-retention strategies will need to be strengthened as national cART programs are expanded and more people require lifelong monitoring and care. PMID:20161344

  14. Suboptimal antiretroviral therapy adherence among HIV-infected adults in Guangzhou, China.

    PubMed

    Muessig, Kathryn E; McLaughlin, Megan M; Nie, Jing Min; Cai, Weiping; Zheng, Heping; Yang, Ligang; Tucker, Joseph D

    2014-01-01

    Despite China's free antiretroviral therapy (ART) program, there are high rates of treatment failure, large sociodemographic disparities in care outcomes and emerging medication resistance. Understanding patient medication adherence behaviors and challenges could inform adherence interventions to maximize the individual and prevention benefits of ART. This study assessed recent nonadherence and treatment interruption among 813 HIV-infected adult outpatients in Guangzhou, China. Participants completed a behavioral survey, underwent chart review, and were tested for syphilis, gonorrhea, and chlamydia. Factors associated with suboptimal adherence were identified using univariate and multivariate logistic regression. Among 721 HIV-infected adults receiving ART, 18.9% reported recent nonadherence (any missed ART in the past four weeks) and 6.8% reported treatment interruption (four or more weeks of missed ART in the past year). Lower education, living alone, alcohol use, and being on ART one to three years were associated with recent nonadherence. Male gender, lower education, and being on ART one to three years were associated with treatment interruption. ART medication adherence interventions are needed in China that include individualized, long-term adherence plans sensitive to patients' educational and economic situations. These interventions should also consider possible gender disparities in treatment outcomes and address the use of alcohol during ART. Successful ART medication adherence interventions in China can inform other international settings that face similar adherence challenges and disparities.

  15. Retention in care and medication adherence: current challenges to antiretroviral therapy success.

    PubMed

    Holtzman, Carol W; Brady, Kathleen A; Yehia, Baligh R

    2015-04-01

    Health behaviors such as retention in HIV medical care and adherence to antiretroviral therapy (ART) pose major challenges to reducing new HIV infections, addressing health disparities, and improving health outcomes. Andersen's Behavioral Model of Health Service Use provides a conceptual framework for understanding how patient and environmental factors affect health behaviors and outcomes, which can inform the design of intervention strategies. Factors affecting retention and adherence among persons with HIV include patient predisposing factors (e.g., mental illness, substance abuse), patient-enabling factors (e.g., social support, reminder strategies, medication characteristics, transportation, housing, insurance), and healthcare environment factors (e.g., pharmacy services, clinic experiences, provider characteristics). Evidence-based recommendations for improving retention and adherence include (1) systematic monitoring of clinic attendance and ART adherence; (2) use of peer or paraprofessional navigators to re-engage patients in care and help them remain in care; (3) optimization of ART regimens and pharmaceutical supply chain management systems; (4) provision of reminder devices and tools; (5) general education and counseling; (6) engagement of peer, family, and community support groups; (7) case management; and (8) targeting patients with substance abuse and mental illness. Further research is needed on effective monitoring strategies and interventions that focus on improving retention and adherence, with specific attention to the healthcare environment. PMID:25792300

  16. Infectious diarrhoea in antiretroviral therapy-naïve HIV/AIDS patients in Kenya

    PubMed Central

    Wanyiri, Jane W.; Kanyi, Henry; Maina, Samuel; Wang, David E.; Ngugi, Paul; O'Connor, Roberta; Kamau, Timothy; Waithera, Tabitha; Kimani, Gachuhi; Wamae, Claire N.; Mwamburi, Mkaya; Ward, Honorine D.

    2013-01-01

    Background Diarrhoea is a significant cause of morbidity and mortality in immunocompromised patients. The objectives of this study were to investigate the aetiological agents, risk factors and clinical features associated with diarrhoea in HIV/AIDS patients in Kenya. Methods Sociodemographic, epidemiological and clinical data were obtained for 164 HIV/AIDS patients (70 with and 94 without diarrhoea) recruited from Kenyatta National Hospital, Kenya. Stool samples were examined for enteric pathogens by microscopy and bacteriology. Results Intestinal protozoa and fungi were identified in 70% of patients, more frequently in those with diarrhoea (p<0.001). Helminths were detected in 25.6% of patients overall, and bacterial pathogens were identified in 51% of patients with diarrhoea. Polyparasitism was more common in patients with diarrhoea than those without (p<0.0001). Higher CD4+ T-cell count (OR = 0.995, 95% CI 0.992–0.998) and water treatment (OR = 0.231, 95% CI 0.126–0.830) were associated with a lower risk of diarrhoea, while close contact with cows (OR = 3.200, 95% CI 1.26–8.13) or pigs (OR = 11.176, 95% CI 3.76–43.56) were associated with a higher risk of diarrhoea. Conclusions Multiple enteric pathogens that are causative agents of diarrhoea were isolated from stools of antiretroviral therapy-naïve HIV/AIDS patients, indicating a need for surveillance, treatment and promotion of hygienic practices. PMID:24026463

  17. The Influence of Medication Attitudes on Utilization of Antiretroviral Therapy (ART) in Indonesian Prisons.

    PubMed

    Culbert, Gabriel J; Bazazi, Alexander R; Waluyo, Agung; Murni, Astia; Muchransyah, Azalia P; Iriyanti, Mariska; Finnahari; Polonsky, Maxim; Levy, Judith; Altice, Frederick L

    2016-05-01

    Negative attitudes toward HIV medications may restrict utilization of antiretroviral therapy (ART) in Indonesian prisons where many people living with HIV (PLH) are diagnosed and first offered ART. This mixed-method study examines the influence of medication attitudes on ART utilization among HIV-infected Indonesian prisoners. Randomly-selected HIV-infected male prisoners (n = 102) completed face-to-face in-depth interviews and structured surveys assessing ART attitudes. Results show that although half of participants utilized ART, a quarter of those meeting ART eligibility guidelines did not. Participants not utilizing ART endorsed greater concerns about ART efficacy, safety, and adverse effects, and more certainty that ART should be deferred in PLH who feel healthy. In multivariate analyses, ART utilization was independently associated with more positive ART attitudes (AOR = 1.09, 95 % CI 1.03-1.16, p = 0.002) and higher internalized HIV stigma (AOR = 1.03, 95 % CI 1.00-1.07, p = 0.016). Social marketing of ART is needed to counteract negative ART attitudes that limit ART utilization among Indonesian prisoners. PMID:26400080

  18. Shortcomings of adherence counselling provided to caregivers of children receiving antiretroviral therapy in rural South Africa.

    PubMed

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-03-01

    In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors.

  19. Retention in Care and Medication Adherence: Current Challenges to Antiretroviral Therapy Success

    PubMed Central

    Holtzman, Carol W.; Brady, Kathleen A.; Yehia, Baligh R.

    2015-01-01

    Health behaviors, such as retention in HIV medical care and adherence to antiretroviral therapy (ART), pose major challenges to reducing new HIV infections, addressing health disparities, and improving health outcomes. Andersen's Behavioral Model of Health Service Use provides a conceptual framework for understanding how patient and environmental factors affect health behaviors and outcomes, which can inform the design of intervention strategies. Factors affecting retention and adherence among persons with HIV include patient predisposing factors (e.g. mental illness, substance abuse), patient enabling factors (e.g. social support, reminder strategies, medication characteristics, transportation, housing, insurance), and health care environment factors (e.g. pharmacy services, clinic experiences, provider characteristics). Evidence-based recommendations for improving retention and adherence include 1) systematic monitoring of clinic attendance and ART adherence; 2) use of peer or paraprofessional navigators to re-engage patients in care and help them remain in care; 3) optimization of ART regimens and pharmaceutical supply chain management systems 4) provision of reminder devices and tools; 5) general education and counseling; 6) engagement of peer, family, and community support groups; 7) case management; and 8) targeting patients with substance abuse and mental illness. Further research is needed on effective monitoring strategies and interventions that focus on improving retention and adherence, with specific attention to the health care environment. PMID:25792300

  20. A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

    PubMed Central

    Koenig, Serena P.; Bornstein, Alexandra; Severe, Karine; Fox, Elizabeth; Dévieux, Jessy G.; Severe, Patrice; Joseph, Patrice; Marcelin, Adias; Bright, Dgndy Alexandre; Pham, Ngoc; Cremieux, Pierre; Pape, Jean William

    2015-01-01

    Objective We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin. Design Cohort study of adult patients on ART. Setting GHESKIO Clinic in Port-au-Prince, Haiti. Participants 4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008. Main Outcome Measure Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin. Results In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used. Conclusions If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted. PMID:26562018

  1. Antiretroviral Therapy in Prevention of HIV and TB: Update on Current Research Efforts

    PubMed Central

    Granich, Reuben; Gupta, Somya; Sutha, Amitabh B; Smyth, Caoimhe; Hoos, David; Vitoria, Marco; Simao, Mariangela; Hankins, Catherine; Schwartlander, Bernard; Ridzon, Renee; Bazin, Brigitte; Williams, Brian; Lo, Ying-Ru; McClure, Craig; Montaner, Julio; Hirnschall, Gottfried

    2011-01-01

    There is considerable scientific evidence supporting the use of antiretroviral therapy (ART) in prevention of human immunodeficiency virus (HIV) and tuberculosis (TB) infections. The complex nature of the HIV and TB prevention responses, resource constraints, remaining questions about cost and feasibility, and the need to use a solid evidence base to make policy decisions, and the implementation challenges to translating trial data to operational settings require a well-organised and coordinated response to research in this area. To this end, we aimed to catalogue the ongoing and planned research activities that evaluate the impact of ART plus other interventions on HIV- and/or TB-related morbidity, mortality, risk behaviour, HIV incidence and transmission. Using a limited search methodology, 50 projects were identified examining ART as prevention, representing 5 regions and 52 countries with a global distribution. There are 24 randomised controlled clinical trials with at least 12 large randomised individual or community cluster trials in resource-constrained settings that are in the planning or early implementation stages. There is considerable heterogeneity between studies in terms of methodology, interventions and geographical location. While the identified studies will undoubtedly advance our understanding of the efficacy and effectiveness of ART for prevention, some key questions may remain unanswered or only partially answered. The large number and wide variety of research projects emphasise the importance of this research issue and clearly demonstrate the potential for synergies, partnerships and coordination across funding agencies. PMID:21999779

  2. Obstacles and proposed solutions to effective antiretroviral therapy in resource-limited settings.

    PubMed

    Bartlett, John A; Hornberger, John; Shewade, Ashwini; Bhor, Menaka; Rajagopalan, Rukmini

    2009-01-01

    More than 3 million people were receiving antiretroviral therapy (ART) at the end of 2007, but this number represents only 31% of people clinically eligible for ART in resource-limited settings. The primary objective of this study is to summarize the key obstacles that impede the goal of universal access prevention, care, and treatment. We performed a systematic literature search to review studies that reported barriers to diagnosis and access to treatment of HIV/AIDS in resource-limited countries. Persons living with HIV/ AIDS commonly face economic, sociocultural, and behavioral obstacles to access treatment and care for HIV. A variety of programs to overcome these barriers have been implemented, including efforts to destigmatize HIV/AIDS, enhance treatment literacy, provide income-generation skills, decentralize HIV services, promote gender equality, and adopt a multisectoral approach to optimize limited resources. An understanding of these obstacles and suggested methods to overcome them must be addressed by global policy makers before universal ART access can be achieved.

  3. Current Scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy

    PubMed Central

    Usman, Muhammad; Kandi, Venkataramana

    2016-01-01

    The discovery of the human immunodeficiency virus (HIV) as the causative organism of acquired immunodeficiency syndrome (AIDS) and the inability of modern medicine to find a cure for it has placed HIV as one of the most dreaded pathogens of the 21st century. With millions of people infected with HIV, it was once thought to result in “medical apocalypse”. However, with the advent of antiretroviral therapy (ART), it is now possible to control HIV. Adherence to ART helps to keep the viral load under control and prolong the time of progression to AIDS, resulting in near normal life expectancy. Even with the introduction of ART, a substantial number of patients fail to adhere due to a variety of reasons, including adverse side effects, drug abuse, mental disorders, socioeconomic status, literacy, and social stigma. With the availability of so many options for HIV treatment at each stage of the disease progression, physicians can switch between the treatment regimens to avoid and/or minimize the adverse effects of drugs. Close monitoring, major social reforms, and adequate counselling should also be implemented to circumvent other challenges. PMID:27054050

  4. Declining tuberculosis case notification rates with the scale-up of antiretroviral therapy in Zimbabwe

    PubMed Central

    Harries, A. D.; Sandy, C.; Mutasa-Apollo, T.; Zishiri, C.

    2016-01-01

    Setting: Zimbabwe has a human immunodeficiency virus (HIV) driven tuberculosis (TB) epidemic, with antiretroviral therapy (ART) scaled up in the public sector since 2004. Objective: To determine whether national ART scale-up was associated with annual national TB case notification rates (CNR), stratified by disease type and category, between 2000 and 2013. Design: This was a retrospective study using aggregate data from global reports. Results: The number of people living with HIV and retained on ART from 2004 to 2013 increased from 8400 to 665 299, with ART coverage increasing from <0.5% to 48%. TB CNRs, all types and categories, increased from 2000 to 2003, and declined thereafter from 2004 to 2013. The decreases in annual TB notifications between the highest rates (before 2004) and lowest rates (2013) were all forms of TB (56%), new TB (60%), previously treated TB (53%), new smear-positive pulmonary TB (PTB) (40%), new smear-negative/smear-unknown PTB (58%) and extra-pulmonary TB (58%). Conclusion: Significant declines in TB CNRs were observed during ART scale-up, especially for smear-negative PTB and extra-pulmonary TB. These encouraging national trends support the continued scale-up of ART for people living with HIV as a way of tackling the twin epidemics of HIV/acquired immune-deficiency syndrome and TB in Zimbabwe.

  5. Body mass index changes during highly active antiretroviral therapy in Nigeria.

    PubMed

    Denue, B A; Ikunaiye, P N Y; Denue, C B A

    2014-01-09

    Wasting remains an important condition in HIV-infected patients receiving highly active antiretroviral therapy (HAART). In this study, 120 patients with newly diagnosed HIV infection were prospectively evaluated to determine the effect of HAART on body mass index (BMI). Eighty-nine (83.1%) patients gained weight, 5 (4.7%) had no weight change, and 13 (12.2%) lost weight. There was a significant increase in overweight and obese patients. On multivariate analysis, time-updated CD4 count and higher baseline BMI were associated with a greater increase in BMI. Anaemia at diagnosis was associated with a significant increase in BMI. There were no significant effects of age, sex, disease severity, viral load or educational status on BMI changes. About 27% of the HIV patients presented with weight loss, which emphasizes that weight loss and wasting remain important AIDS-defining conditions, despite the advent of HAART. A linear association was observed between time-updated CD4 count and increase in BMI. The association between time-updated CD4 count and greater increase in BMI suggests that BMI could be a surrogate for CD4 count in monitoring treatment response in resource-limited settings.

  6. Drug–drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems

    PubMed Central

    Rao, PSS; Earla, Ravindra; Kumar, Anil

    2015-01-01

    Introduction Substance abuse is a common problem among HIV-infected individuals. Importantly, addictions as well as moderate use of alcohol, smoking, or other illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy (ART) among HIV patients. The literature also suggests a decrease in the response to ART among HIV patients who use these substances, leading to failure to achieve optimal virological response and increased disease progression. Areas covered This review discusses the challenges with adherence to ART as well as observed drug interactions and known toxicities with major drugs of abuse, such as alcohol, smoking, methamphetamine, cocaine, marijuana, and opioids. The lack of adherence and drug interactions potentially lead to decreased efficacy of ART drugs and increased ART, and drugs of abuse-mediated toxicity. As CYP is the common pathway in metabolizing both ART and drugs of abuse, we discuss the possible involvement of CYP pathways in such drug interactions. Expert opinion We acknowledge that further studies focusing on common metabolic pathways involving CYP and advance research in this area would help to potentially develop novel/alternate interventions and drug dose/regimen adjustments to improve medication outcomes in HIV patients who consume drugs of abuse. PMID:25539046

  7. Antiretroviral therapy and changing patterns of HIV stigmatisation in Entebbe, Uganda.

    PubMed

    Russell, Steve; Zalwango, Flavia; Namukwaya, Stella; Katongole, Joseph; Muhumuza, Richard; Nalugya, Ruth; Seeley, Janet

    2016-01-01

    Antiretroviral therapy (ART) has the potential to change processes of HIV stigmatisation. In this article, changing processes of stigmatisation among a group of people living with HIV (PLWH) on ART in Wakiso District, Uganda, are analysed using qualitative data from a study of PLWH's self-management of HIV on ART. There were 38 respondents (20 women, 18 men) who had been taking ART for at least 1 year. They were purposefully selected from government and non-government ART providers. Two in-depth interviews were held with each participant. Processes of reduced self-stigmatisation were clearly evident, caused by the recovery of their physical appearance and support from health workers. However most participants continued to conceal their status because they anticipated stigma; for example, they feared gossip, rejection and their status being used against them. Anticipated stigma was gendered: women expressed greater fear of enacted forms of stigma such as rejection by their partner; in contrast men's fears focused on gossip, loss of dignity and self-stigmatisation. The evidence indicates that ART has not reduced underlying structural drivers of stigmatisation, notably gender identities and inequalities, and that interventions are still required to mitigate and tackle stigmatisation, such as counselling, peer-led education and support groups that can help PLWH reconstruct alternative and more positive identities. A video abstract of this article can be found at: https://youtu.be/WtIaZJQ3Y_8.

  8. Barriers to and Facilitators of Antiretroviral Therapy Adherence in Nepal: A Qualitative Study

    PubMed Central

    Simkhada, Padam; Randall, Julian; Freeman, Jennifer V; van Teijlingen, Edwin

    2012-01-01

    Patient's adherence is crucial to get the best out of antiretroviral therapy (ART). This study explores in-depth the barriers to and facilitators of ART adherence among Nepalese patients and service providers prescribing ART. Face-to-face semi-structured interviews were conducted with 34 participants. Interviews were audio-taped, transcribed, and translated into English before being analyzed thematically. ART-prescribed patients described a range of barriers for failing to adhere to ART. Financial difficulties, access to healthcare services, frequent transport blockades, religious/ritual obstacles, stigma and discrimination, and side-effects were the most-frequently discussed barriers whereas trustworthy health workers, perceived health benefits, and family support were the most-reported facilitators. Understanding barriers and facilitators can help in the design of an appropriate and targeted intervention. Healthcare providers should address some of the practical and cultural issues around ART whilst policy-makers should develop appropriate social policy to promote adherence among ART-prescribed patients. PMID:23304907

  9. Declining tuberculosis case notification rates with the scale-up of antiretroviral therapy in Zimbabwe

    PubMed Central

    Harries, A. D.; Sandy, C.; Mutasa-Apollo, T.; Zishiri, C.

    2016-01-01

    Setting: Zimbabwe has a human immunodeficiency virus (HIV) driven tuberculosis (TB) epidemic, with antiretroviral therapy (ART) scaled up in the public sector since 2004. Objective: To determine whether national ART scale-up was associated with annual national TB case notification rates (CNR), stratified by disease type and category, between 2000 and 2013. Design: This was a retrospective study using aggregate data from global reports. Results: The number of people living with HIV and retained on ART from 2004 to 2013 increased from 8400 to 665 299, with ART coverage increasing from <0.5% to 48%. TB CNRs, all types and categories, increased from 2000 to 2003, and declined thereafter from 2004 to 2013. The decreases in annual TB notifications between the highest rates (before 2004) and lowest rates (2013) were all forms of TB (56%), new TB (60%), previously treated TB (53%), new smear-positive pulmonary TB (PTB) (40%), new smear-negative/smear-unknown PTB (58%) and extra-pulmonary TB (58%). Conclusion: Significant declines in TB CNRs were observed during ART scale-up, especially for smear-negative PTB and extra-pulmonary TB. These encouraging national trends support the continued scale-up of ART for people living with HIV as a way of tackling the twin epidemics of HIV/acquired immune-deficiency syndrome and TB in Zimbabwe. PMID:27695678

  10. Explaining Antiretroviral Therapy Adherence Success Among HIV-Infected Children in Rural Uganda: A Qualitative Study

    PubMed Central

    Olds, Peter K.; Kiwanuka, Julius P.; Ware, Norma C.; Tsai, Alexander C.

    2014-01-01

    High adherence is critical for achieving clinical benefits of HIV antiretroviral therapy (ART) and particularly challenging for children. We conducted 35 qualitative interviews with caregivers of HIV-infected Ugandan children who were followed in a longitudinal study of real-time ART adherence monitoring; 18 participants had undetectable HIV RNA, while 17 had detectable virus. Interviews blinded to viral suppression status elicited information on adherence experiences, barriers and facilitators to adherence, and social support. Using an inductive content analytic approach, we identified ‘lack of resources,’ ‘Lazarus effect,’ ‘caregiver's sense of obligation and commitment,’ and ‘child's personal responsibility’ as categories of influence on adherence, and defined types of caregiver social support. Among children with viral suppression, high hopes for the child's future and ready access to private instrumental support appeared particularly important. These findings suggest clinical counseling should explore caregivers' views of their children's futures and ability to access support in overcoming adherence barriers. PMID:25323679

  11. Factors impacting the provision of antiretroviral therapy to people living with HIV: the view from Haiti.

    PubMed

    Rouzier, Vanessa; Farmer, Paul E; Pape, Jean W; Jerome, Jean-Gregory; Van Onacker, Joelle Deas; Morose, Willy; Joseph, Patrice; Leandre, Fernet; Severe, Patrice; Barry, Donna; Deschamps, Marie-Marcelle; Koenig, Serena P

    2014-01-01

    Haiti is the poorest country in the Western Hemisphere and has the highest number of people living with HIV in the Caribbean, the region most impacted by HIV outside of Africa. Despite continuous political, socioeconomic and natural catastrophes, Haiti has mounted a very successful response to the HIV epidemic. Prevention and treatment strategies implemented by the government in collaboration with non-governmental organizations have been instrumental in decreasing the national HIV prevalence from a high of 6.2% in 1993 to 2.2% in 2012. We describe the history and epidemiology of HIV in Haiti and the expansion of antiretroviral therapy (ART) over the past decade, with the achievement of universal access to ART for patients meeting the 2010 World Health Organization guidelines. We also describe effective models of care, successes and challenges of international funding, and current challenges in the provision of ART. We are optimistic that the goal of providing ART for all in need remains in reach. PMID:25310257

  12. The Influence of Medication Attitudes on Utilization of Antiretroviral Therapy (ART) in Indonesian Prisons.

    PubMed

    Culbert, Gabriel J; Bazazi, Alexander R; Waluyo, Agung; Murni, Astia; Muchransyah, Azalia P; Iriyanti, Mariska; Finnahari; Polonsky, Maxim; Levy, Judith; Altice, Frederick L

    2016-05-01

    Negative attitudes toward HIV medications may restrict utilization of antiretroviral therapy (ART) in Indonesian prisons where many people living with HIV (PLH) are diagnosed and first offered ART. This mixed-method study examines the influence of medication attitudes on ART utilization among HIV-infected Indonesian prisoners. Randomly-selected HIV-infected male prisoners (n = 102) completed face-to-face in-depth interviews and structured surveys assessing ART attitudes. Results show that although half of participants utilized ART, a quarter of those meeting ART eligibility guidelines did not. Participants not utilizing ART endorsed greater concerns about ART efficacy, safety, and adverse effects, and more certainty that ART should be deferred in PLH who feel healthy. In multivariate analyses, ART utilization was independently associated with more positive ART attitudes (AOR = 1.09, 95 % CI 1.03-1.16, p = 0.002) and higher internalized HIV stigma (AOR = 1.03, 95 % CI 1.00-1.07, p = 0.016). Social marketing of ART is needed to counteract negative ART attitudes that limit ART utilization among Indonesian prisoners.

  13. Bacillary angiomatosis in a HIV-positive patient with poor adherence to antiretroviral therapy.

    PubMed

    Lopes, Leonor; Borges-Costa, João; Janeiro, Nuno; Neves, Diana; Soares Almeida, Luís; Filipe, Paulo

    2014-01-01

    Bacillary angiomatosis is a systemic disease caused by Bartonella (B.) henselae and B. quintana. Today it is a rare disease that occurs predominantly in patients with poor adherence to antiretroviral therapy or with late diagnosis of human immunodeficiency virus (HIV). We report on the case of a 40-year-old Caucasian female with HIV-1 and hepatitis B virus (HBV) co-infection diagnosed 17 years ago. She presented to the emergency department with an erythematous, painless nodule located on the left naso-genian fold. In the next few weeks the disease disseminated to the oral and left tarsal mucosa and to the palm of the left hand. The histopathological findings were suggestive of bacillary angiomatosis which was confirmed by polymerase chain reaction (PCR). The patient was treated with clarithromycin 500 mg bid per os for 3 months, with complete remission of the mucocutaneous lesions. Bacillary angiomatosis is a potentially fatal disease. Early diagnosis and treatment are critical in reducing the morbidity and mortality associated with it.

  14. Antiretroviral Therapy Use, Medication Adherence, and Viral Suppression Among PLWHA with Panic Symptoms.

    PubMed

    Sam, Tanyka Suzanne; Hutton, Heidi E; Lau, Bryan; McCaul, Mary E; Keruly, Jeanne; Moore, Richard; Chander, Geetanjali

    2015-11-01

    Panic symptoms are prevalent among PLWHAs, yet few studies have examined their relationship with HIV outcomes. Using data from an observational cohort study in Baltimore, MD, we examined the association between panic symptoms and antiretroviral therapy (ART) use, medication adherence, and viral suppression. Data were analyzed using generalized estimating equations and adjusted for age, sex, race/ethnicity, cocaine and/or heroin use, clinic enrollment time, alcohol use, and depressive symptoms. Between June 2010 and September 2012, 1195 individuals participated in 2080 audio computer assisted interviews; 9.9 % (n = 118) of individuals endorsed current panic symptoms. In multivariate analysis, panic symptoms were associated with decreased ART use (IRR 0.94; p = 0.05). Panic symptoms were neither associated with medication adherence nor viral suppression. These findings were independent of depressive symptoms and substance use. Panic symptoms are under-recognized in primary care settings and present an important barrier to ART use. Further studies investigating the reasons for this association are needed.

  15. Anxiety and depression symptoms as risk factors for non-adherence to antiretroviral therapy in Brazil

    PubMed Central

    Campos, Lorenza Nogueira; Guimarães, Mark Drew Crosland; Remien, Robert H.

    2009-01-01

    Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n=293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH=1.87; 95% CI=1.14–3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life. PMID:18648925

  16. Functional proteome of macrophage carried nanoformulated antiretroviral therapy demonstrates enhanced particle carrying capacity.

    PubMed

    Martinez-Skinner, Andrea L; Veerubhotla, Ram S; Liu, Han; Xiong, Huangui; Yu, Fang; McMillan, JoEllyn M; Gendelman, Howard E

    2013-05-01

    Our laboratory developed long-acting nanoformulations of antiretroviral therapy (nanoART) to improve drug compliance, reduce toxicities, and facilitate access of drug to viral reservoirs. These all function to inevitably improve treatment of human immunodeficiency virus (HIV) infection. Formulations are designed to harness the carrying capacities of mononuclear phagocytes (MP; monocytes and macrophages) and to use these cells as Trojan horses for drug delivery. Such a drug distribution system limits ART metabolism and excretion while facilitating access to viral reservoirs. Our prior works demonstrated a high degree of nanoART sequestration in macrophage recycling endosomes with broad and sustained drug tissue biodistribution and depots with limited untoward systemic toxicities. Despite such benefits, the effects of particle carriage on the cells' functional capacities remained poorly understood. Thus, we employed pulsed stable isotope labeling of amino acids in cell culture to elucidate the macrophage proteome and assess any alterations in cellular functions that would affect cell-drug carriage and release kinetics. NanoART-MP interactions resulted in the induction of a broad range of activation-related proteins that can enhance phagocytosis, secretory functions, and cell migration. Notably, we now demonstrate that particle-cell interactions serve to enhance drug loading while facilitating drug tissue depots and transportation. PMID:23544708

  17. Initiation of Antiretroviral Therapy in Youth with HIV: A U.S.-Based Provider Survey

    PubMed Central

    Murray, Meghan; Saiman, Lisa; Neu, Natalie

    2013-01-01

    Abstract In 2009, the Department of Health and Human Services (DHHS) recommended initiating antiretroviral therapy (ART) for youth with HIV at higher CD4 counts (≤500 cells/mm3) than previously recommended (≤350 cells/mm3). Barriers experienced by providers regarding ART initiation in this population have not been assessed. From 12/2011–01/2012, we asked providers from the HIV Medicine Association listserv who prescribed ART to youth (ages 13–25 years) with behaviorally-acquired HIV to complete a web-based survey. We presented a clinical vignette to explore potential barriers for initiating ART. Overall, 274/290 (94%) respondents completed the survey. Most felt confident that evidence supported initiating ART at higher CD4 counts (94%), and that benefits outweighed the risks of long-term toxicity (98%) or developing resistance (88%). Most (96%) initiated ART in the patient vignette (age 19 years, CD4 count ∼400). Patient characteristics (e.g., unstable housing or drug use) were perceived as large barriers to ART initiation. Low response rate (13%) was a limitation. Respondents were knowledgeable about relevant DHHS guidelines, believed sufficient evidence supported ART initiation at higher CD4 counts, and would provide treatment to those with CD4 counts ≤500cells/mm3. Understanding and overcoming barriers to initiation of ART perceived by providers is important to ensure implementation of ART treatment guidelines. PMID:23937549

  18. Current Scenario of HIV/AIDS, Treatment Options, and Major Challenges with Compliance to Antiretroviral Therapy.

    PubMed

    Bhatti, Adnan Bashir; Usman, Muhammad; Kandi, Venkataramana

    2016-01-01

    The discovery of the human immunodeficiency virus (HIV) as the causative organism of acquired immunodeficiency syndrome (AIDS) and the inability of modern medicine to find a cure for it has placed HIV as one of the most dreaded pathogens of the 21(st) century. With millions of people infected with HIV, it was once thought to result in "medical apocalypse". However, with the advent of antiretroviral therapy (ART), it is now possible to control HIV. Adherence to ART helps to keep the viral load under control and prolong the time of progression to AIDS, resulting in near normal life expectancy. Even with the introduction of ART, a substantial number of patients fail to adhere due to a variety of reasons, including adverse side effects, drug abuse, mental disorders, socioeconomic status, literacy, and social stigma. With the availability of so many options for HIV treatment at each stage of the disease progression, physicians can switch between the treatment regimens to avoid and/or minimize the adverse effects of drugs. Close monitoring, major social reforms, and adequate counselling should also be implemented to circumvent other challenges. PMID:27054050

  19. Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis.

    PubMed

    Hoenigl, Martin; Chaillon, Antoine; Moore, David J; Morris, Sheldon R; Mehta, Sanjay R; Gianella, Sara; Amico, K Rivet; Little, Susan J

    2016-01-01

    Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used. PMID:27597312

  20. Cannabis use and HIV antiretroviral therapy adherence and HIV-related symptoms.

    PubMed

    Bonn-Miller, Marcel O; Oser, Megan L; Bucossi, Meggan M; Trafton, Jodie A

    2014-02-01

    Occasional cannabis use has been associated with increased antiretroviral therapy (ART) adherence and relief of HIV symptoms, while heavy use has been associated with low ART adherence and negative psychological symptoms. The purpose of the present study was to investigate differences between non-cannabis use (NC), non-dependent cannabis use (C), and dependent use (CD) in terms of ART adherence and HIV symptoms/ART side effects. A cross-sectional sample of 180 HIV+ individuals (78.3 % male) completed measures of substance use and psychopathology, medication adherence, and HIV symptoms/ART side effects. Adherence was also measured via pill count, viral load, and CD4 count. Results indicated that the CD group reported lower adherence and greater HIV symptoms/ART side effects than the other two groups, with no differences observed between NC and C groups. There is a clinical need to address dependent cannabis use among those prescribed ART. Further examination is needed to ascertain the functions of cannabis use among individuals with HIV.

  1. Antiretroviral Therapy Use, Medication Adherence, and Viral Suppression Among PLWHA with Panic Symptoms.

    PubMed

    Sam, Tanyka Suzanne; Hutton, Heidi E; Lau, Bryan; McCaul, Mary E; Keruly, Jeanne; Moore, Richard; Chander, Geetanjali

    2015-11-01

    Panic symptoms are prevalent among PLWHAs, yet few studies have examined their relationship with HIV outcomes. Using data from an observational cohort study in Baltimore, MD, we examined the association between panic symptoms and antiretroviral therapy (ART) use, medication adherence, and viral suppression. Data were analyzed using generalized estimating equations and adjusted for age, sex, race/ethnicity, cocaine and/or heroin use, clinic enrollment time, alcohol use, and depressive symptoms. Between June 2010 and September 2012, 1195 individuals participated in 2080 audio computer assisted interviews; 9.9 % (n = 118) of individuals endorsed current panic symptoms. In multivariate analysis, panic symptoms were associated with decreased ART use (IRR 0.94; p = 0.05). Panic symptoms were neither associated with medication adherence nor viral suppression. These findings were independent of depressive symptoms and substance use. Panic symptoms are under-recognized in primary care settings and present an important barrier to ART use. Further studies investigating the reasons for this association are needed. PMID:25903506

  2. The impact of antiretroviral therapy in resource-limited settings and current HIV therapeutics.

    PubMed

    Kumarasamy, N

    2016-04-01

    Four million people of the global total of 35 million with HIV infection are from South-East Asia. ART is currently utilized by 15 million people and has led to a dramatic decline in the mortality rate, including those in low- and middle-income countries. A reduction in sexually transmitted HIV and in comorbidities including tuberculosis has also followed. Current recommendations for the initiation of antiretroviral therapy in people who are HIV+ are essentially to initiate ART irrespective of CD4 cell count and clinical stage. The frequency of HIV testing should be culturally specific and based on the HIV incidence in different key populations but phasing in viral load technology in LMIC is an urgent priority and this needs resources and capacity. With the availability of simplified potent ART regimens, persons with HIV now live longer. The recent WHO treatment guidelines recommending routine HIV testing and earlier initiation of treatment should be the stepping stone for ending the AIDS epidemic and to meet the UNAIDS mission of 90*90*90.

  3. Low-Cost Method to Monitor Patient Adherence to HIV Antiretroviral Therapy Using Multiplex Cathepsin Zymography.

    PubMed

    Platt, Manu O; Evans, Denise; Keegan, Philip M; McNamara, Lynne; Parker, Ivana K; Roberts, LaDeidra M; Caulk, Alexander W; Gleason, Rudolph L; Seifu, Daniel; Amogne, Wondwossen; Penny, Clement

    2016-01-01

    Monitoring patient adherence to HIV antiretroviral therapy (ART) by patient survey is inherently error prone, justifying a need for objective, biological measures affordable in low-resource settings where HIV/AIDS epidemic is highest. In preliminary studies conducted in Ethiopia and South Africa, we observed loss of cysteine cathepsin activity in peripheral blood mononuclear cells of HIV-positive patients on ART. We optimized a rapid protocol for multiplex cathepsin zymography to quantify cysteine cathepsins, and prospectively enrolled 350 HIV-positive, ART-naïve adults attending the Themba Lethu Clinic, Johannesburg, South Africa, to test if suppressed cathepsin activity could be a biomarker of ART adherence (103 patients were included in final analysis). Poor adherence was defined as detectable viral load (>400 copies/ml) or simplified medication adherence questionnaire, 4-6 months after ART initiation. 86 % of patients with undetectable viral loads after 6 months were cathepsin negative, and cathepsin-positive patients were twice as likely to have detectable viral loads (RR 2.32 95 % CI 1.26-4.29). Together, this demonstrates proof of concept that multiplex cathepsin zymography may be an inexpensive, objective method to monitor patient adherence to ART. Low cost of this electrophoresis-based assay makes it a prime candidate for implementation in resource-limited settings. PMID:26589706

  4. Comorbidities associated with HIV and antiretroviral therapy (clinical sciences): a workshop report.

    PubMed

    Vernon, L T; Jayashantha, Plp; Chidzonga, M M; Komesu, M C; Nair, R G; Johnson, N W

    2016-04-01

    In the era of combination antiretroviral therapy (ART), parsing out the effects of HIV vs ART on health outcomes is challenging. Nadir CD4 count, a marker of the extent of immunosuppression, has significant long-term impact on an array of disease states in HIV+ persons; however, in the dental literature, reporting of pre-ART exposure to immunosuppression has largely been ignored and this limits the validity of previous studies. In Workshop A1, we explain fully the importance of nadir CD4, pre-ART immunosuppression, and identify a need to include specific variables in future research. The questions posed herein are challenging, typically not neatly addressed by any one study and require integration of the latest evidence from the wider medical literature. We consider topics beyond the confines of the oral cavity and examine oral health in the complex context of ART era HIV immunopathophysiology. We depict how variability in geographic setting and time period (pre- and post-ART era) can impact oral conditions - influencing when HIV infection was detected (at what CD4 count), the type and timing of ART as well as social determinants such as strong stigma and limited access to care. We hope our Workshop will stir debate and energize a rigorous focus on relevant areas of future research in HIV/AIDS. PMID:27109282

  5. Rapid HIV Viral Load Suppression in those Initiating Antiretroviral Therapy at First Visit after HIV Diagnosis

    PubMed Central

    Hoenigl, Martin; Chaillon, Antoine; Moore, David J.; Morris, Sheldon R.; Mehta, Sanjay R.; Gianella, Sara; Amico, K. Rivet; Little, Susan J.

    2016-01-01

    Expert guidelines for antiretroviral therapy (ART) now recommend ART as soon as possible in all HIV infected persons to reduce the risk of disease progression and prevent transmission. The goal of this observational study was to evaluate the impact of very early ART initiation and regimen type on time to viral suppression. We evaluated time to viral suppression among 86 persons with newly-diagnosed HIV infection who initiated ART within 30 days of diagnosis. A total of 36 (42%) had acute, 27 (31%) early, and 23 (27%) had established HIV infection. The median time from an offer of immediate ART to starting ART was 8 days. A total of 56/86 (65%) initiated an integrase inhibitor-based regimen and 30/86 (35%) a protease inhibitor-based regimen. The time to viral suppression was significantly shorter in those receiving an integrase inhibitor- versus a protease inhibitor-based regimen (p = 0.022). Twenty-two (26%) initiated ART at their HIV care intake visit and 79% of these participants achieved viral suppression at week 12, 82% at week 24 and 88% at week 48. ART initiated at the intake visit led to rapid and reliable viral suppression in acute, early and chronic HIV infection, in particular when integrase inhibitor-based regimens were used. PMID:27597312

  6. Neurocognitive Change in the Era of HIV Combination Antiretroviral Therapy: The Longitudinal CHARTER Study

    PubMed Central

    Heaton, Robert K.; Franklin, Donald R.; Deutsch, Reena; Letendre, Scott; Ellis, Ronald J.; Casaletto, Kaitlin; Marquine, Maria J.; Woods, Steven P.; Vaida, Florin; Atkinson, J. Hampton; Marcotte, Thomas D.; McCutchan, J. Allen; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; Sacktor, Ned; Morgello, Susan; Simpson, David M.; Abramson, Ian; Gamst, Anthony C.; Fennema-Notestine, Christine; Smith, David M.; Grant, Igor; Grant, Igor; McCutchan, J. Allen; Ellis, Ronald J.; Marcotte, Thomas D.; Franklin, Donald; Ellis, Ronald J.; McCutchan, J. Allen; Alexander, Terry; Letendre, Scott; Capparelli, Edmund; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; Dawson, Matthew; Smith, David M.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Marcotte, Thomas D.; Marquie-Beck, Jennifer; McArthur, Justin; Rogalski, Vincent; Morgello, Susan; Simpson, David; Mintz, Letty; McCutchan, J. Allen; Toperoff, Will; Collier, Ann; Marra, Christina; Jones, Trudy; Gelman, Benjamin; Head, Eleanor; Clifford, David; Al-Lozi, Muhammad; Teshome, Mengesha

    2015-01-01

    Background. Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) can show variable clinical trajectories. Previous longitudinal studies of HAND typically have been brief, did not use adequate normative standards, or were conducted in the context of a clinical trial, thereby limiting our understanding of incident neurocognitive (NC) decline and recovery. Methods. We investigated the incidence and predictors of NC change over 16–72 (mean, 35) months in 436 HIV-infected participants in the CNS HIV Anti-Retroviral Therapy Effects Research cohort. Comprehensive laboratory, neuromedical, and NC assessments were obtained every 6 months. Published, regression-based norms for NC change were used to generate overall change status (decline vs stable vs improved) at each study visit. Survival analysis was used to examine the predictors of time to NC change. Results. Ninety-nine participants (22.7%) declined, 265 (60.8%) remained stable, and 72 (16.5%) improved. In multivariable analyses, predictors of NC improvements or declines included time-dependent treatment status and indicators of disease severity (current hematocrit, albumin, total protein, aspartate aminotransferase), and baseline demographics and estimated premorbid intelligence quotient, non-HIV-related comorbidities, current depressive symptoms, and lifetime psychiatric diagnoses (overall model P < .0001). Conclusions. NC change is common in HIV infection and appears to be driven by a complex set of risk factors involving HIV disease, its treatment, and comorbid conditions. PMID:25362201

  7. Shortcomings of adherence counselling provided to caregivers of children receiving antiretroviral therapy in rural South Africa

    PubMed Central

    Coetzee, Bronwyne; Kagee, Ashraf; Bland, Ruth

    2016-01-01

    ABSTRACT In order to achieve optimal benefits of antiretroviral therapy (ART), caregivers of children receiving ART are required to attend routine clinic visits monthly and administer medication to the child as prescribed. Yet, the level of adherence to these behaviours varies considerably in many settings. As a way to achieve optimal adherence in rural KwaZulu-Natal, caregivers are required to attend routine counselling sessions at HIV treatment clinics that are centred on imparting information, motivation, and behavioural skills related to medication administration. According to the information-motivation-behavioural skills model, information related to adherence, motivation, and behavioural skills are necessary and fundamental determinants of adherence to ART. The purpose of the study was to observe and document the content of adherence counselling sessions that caregivers attending rural clinics in KwaZulu Natal receive. We observed 25 adherence counselling sessions, which lasted on average 8.1 minutes. Counselling typically consisted of counsellors recording patient attendance, reporting CD4 count and viral load results to caregivers, emphasising dose times, and asking caregivers to name their medications and dosage amounts. Patients were seldom asked to demonstrate how they measure the medication. They were also not probed for problems regarding treatment, even when an unsuppressed VL was reported to a caregiver. This paper calls attention to the sub-optimal level of counselling provided to patients on ART and the urgent need to standardise and improve the training, support, and debriefing provided to counsellors. PMID:27392000

  8. Will universal access to antiretroviral therapy ever be possible? The health care worker challenge.

    PubMed

    Maddison, André R; Schlech, Walter F

    2010-01-01

    The United Nations millennium development goal of providing universal access to antiretroviral therapy (ART) for patients living with HIV/AIDS by 2010 is unachievable. Currently, four million people are receiving ART, of an estimated 13.7 million who need it. A major challenge to achieving this goal is the shortage of health care workers in low-income and low-resource areas of the world. Sub-Saharan African countries have 68% of the world's burden of illness from AIDS, yet have only 3% of health care workers worldwide. The shortage of health care providers is primarily caused by a national and international 'brain drain,' poor distribution of health care workers within countries, and health care worker burnout.Even though the millennium development goal to provide universal access to ART will not be met by 2010, it is imperative to continue to build on the momentum created by these humanitarian goals. The present literature review was written with the purpose of attracting research and policy attention toward evidence from small-scale projects in sub-Saharan Africa, which have been successful at increasing access to ART. Specifically, a primary-care model of ART delivery, which focuses on decentralization of services, task shifting and community involvement will be discussed. To improve the health care worker shortage in sub-Saharan Africa, the conventional model of health care delivery must be replaced with an innovative model that utilizes doctors, nurses and community members more effectively.

  9. Non-communicable diseases in antiretroviral therapy recipients in Kagera Tanzania: a cross-sectional study

    PubMed Central

    Magafu, Mgaywa Gilbert Mjungu Damas; Moji, Kazuhiko; Igumbor, Ehimario Uche; Magafu, Naoko Shimizu; Mwandri, Michael; Mwita, Julius Chacha; Habte, Dereje; Rwegerera, Godfrey Mutashambara; Hashizume, Masahiro

    2013-01-01

    Introduction The aim of this study was to describe the extent of self-reported non-communicable diseases (NCDs) among highly active antiretroviral therapy (HAART) recipients in Kagera region in Tanzania and their effect on health-related quality of life (HRQOL). This study was conducted 2 years after HAART administration was started in Kagera region. Methods The SF-36 questionnaire was used to collect the HRQOL data of 329 HAART recipients. Questions on the NCDs, socio-demographic characteristics and treatment information were validated and added to the SF-36. Bivariate analyses involving socio-demographic characteristics and SF-36 scores of the recipients were performed. Multiple logistic regression was employed to compute adjusted odds ratios for different explanatory variables on physical functioning and mental health scores. Results Respondents who reported having 1 or more NCDs were 57.8% of all the respondents. Arthritis was the commonest NCD (57.8%). Respondents with the NCDs were more likely to have HRQOL scores below the mean of the general Tanzanian population. The population attributable fraction (PAF) for the NCDs on physical functioning was 0.28 and on mental health was 0.22. Conclusion Self-reported NCDs were prevalent among the HAART recipients in Kagera region. They accounted for 28% of the physical functioning scores and 22% of the mental health scores that were below the mean of the general Tanzanian population. Therefore, the integration of NCD care is important in the management of HIV/AIDS. PMID:24711874

  10. Monitoring the scale-up of antiretroviral therapy programmes: methods to estimate coverage.

    PubMed Central

    Boerma, J. Ties; Stanecki, Karen A.; Newell, Marie-Louise; Luo, Chewe; Beusenberg, Michel; Garnett, Geoff P.; Little, Kirsty; Calleja, Jesus Garcia; Crowley, Siobhan; Kim, Jim Yong; Zaniewski, Elizabeth; Walker, Neff; Stover, John; Ghys, Peter D.

    2006-01-01

    This paper reviews the data sources and methods used to estimate the number of people on, and coverage of, antiretroviral therapy (ART) programmes in low- and middle-income countries and to monitor the progress towards the "3 by 5" target set by WHO and UNAIDS. We include a review of the data sources used to estimate the coverage of ART programmes as well as the efforts made to avoid double counting and over-reporting. The methods used to estimate the number of people in need of ART are described and expanded with estimates of treatment needs for children, both for ART and for cotrimoxazole prophylaxis. An estimated 6.5 million people were in need of treatment in low- and middle-income countries by the end of 2004, including 660,000 children under age 15 years. The mid-2005 estimate of 970,000 people receiving ART in low- and middle-income countries (with an uncertainty range 840,000-1,100,000) corresponds to a coverage of 15% of people in need of treatment. PMID:16501733

  11. Health outcomes among HIV-positive Latinos initiating antiretroviral therapy in North America versus Central and South America

    PubMed Central

    Cesar, Carina; Koethe, John R; Giganti, Mark J; Rebeiro, Peter; Althoff, Keri N; Napravnik, Sonia; Mayor, Angel; Grinsztejn, Beatriz; Wolff, Marcelo; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Sterling, Timothy R; Willig, James; Levison, Julie; Kitahata, Mari; Rodriguez-Barradas, Maria C; Moore, Richard D; McGowan, Catherine; Shepherd, Bryan E; Cahn, Pedro

    2016-01-01

    Introduction Latinos living with HIV in the Americas share a common ethnic and cultural heritage. In North America, Latinos have a relatively high rate of new HIV infections but lower rates of engagement at all stages of the care continuum, whereas in Latin America antiretroviral therapy (ART) services continue to expand to meet treatment needs. In this analysis, we compare HIV treatment outcomes between Latinos receiving ART in North America versus Latin America. Methods HIV-positive adults initiating ART at Caribbean, Central and South America Network for HIV (CCASAnet) sites were compared to Latino patients (based on country of origin or ethnic identity) starting treatment at North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) sites in the United States and Canada between 2000 and 2011. Cox proportional hazards models compared mortality, treatment interruption, antiretroviral regimen change, virologic failure and loss to follow-up between cohorts. Results The study included 8400 CCASAnet and 2786 NA-ACCORD patients initiating ART. CCASAnet patients were younger (median 35 vs. 37 years), more likely to be female (27% vs. 20%) and had lower nadir CD4 count (median 148 vs. 195 cells/µL, p<0.001 for all). In multivariable analyses, CCASAnet patients had a higher risk of mortality after ART initiation (adjusted hazard ratio (AHR) 1.61; 95% confidence interval (CI): 1.32 to 1.96), particularly during the first year, but a lower hazard of treatment interruption (AHR: 0.46; 95% CI: 0.42 to 0.50), change to second-line ART (AHR: 0.56; 95% CI: 0.51 to 0.62) and virologic failure (AHR: 0.52; 95% CI: 0.48 to 0.57). Conclusions HIV-positive Latinos initiating ART in Latin America have greater continuity of treatment but are at higher risk of death than Latinos in North America. Factors underlying these differences, such as HIV testing, linkage and access to care, warrant further investigation. PMID:26996992

  12. Relationship between viral load and behavioral measures of adherence to antiretroviral therapy in children living with human immunodeficiency virus in Latin America.

    PubMed

    Duarte, Horacio A; Harris, Donald Robert; Tassiopoulos, Katherine; Leister, Erin; Negrini, Silvia Fabiana Biason de Moura; Ferreira, Flávia Faleiro; Cruz, Maria Letícia Santos; Pinto, Jorge; Allison, Susannah; Hazra, Rohan

    2015-01-01

    Few studies have examined antiretroviral therapy adherence in Latin American children. Standardized behavioral measures were applied to a large cohort of human immunodeficiency virus-infected children in Brazil, Mexico, and Peru to assess adherence to prescribed antiretroviral therapy doses during the three days prior to study visits, assess timing of last missed dose, and evaluate the ability of the adherence measures to predict viral suppression. Time trends in adherence were modeled using a generalized estimating equations approach to account for possible correlations in outcomes measured repeatedly in the same participants. Associations of adherence with human immunodeficiency virus viral load were examined using linear regression. Mean enrollment age of the 380 participants was 5 years; 57.6% had undetectable' viral load (<400 copies/mL). At enrollment, 90.8% of participants were perfectly (100%) adherent, compared to 87.6% at the 6-month and 92.0% at the 12-month visit; the proportion with perfect adherence did not differ over time (p=0.1). Perfect adherence was associated with a higher probability of undetectable viral load at the 12-month visit (odds ratio=4.1, 95% confidence interval: 1.8-9.1; p<0.001), but not at enrollment or the 6-month visit (p>0.3). Last time missed any antiretroviral therapy dose was reported as "never" for 52.0% at enrollment, increasing to 60.7% and 65.9% at the 6- and 12-month visits, respectively (p<0.001 for test of trend). The proportion with undetectable viral load was higher among those who never missed a dose at enrollment and the 12-month visit (p≤0.005), but not at the 6-month visit (p=0.2). While antiretroviral therapy adherence measures utilized in this study showed some association with viral load for these Latin American children, they may not be adequate for reliably identifying non-adherence and consequently children at risk for viral resistance. Other strategies are needed to improve the evaluation of adherence in

  13. A three-tier framework for monitoring antiretroviral therapy in high HIV burden settings

    PubMed Central

    Osler, Meg; Hilderbrand, Katherine; Hennessey, Claudine; Arendse, Juanita; Goemaere, Eric; Ford, Nathan; Boulle, Andrew

    2014-01-01

    The provision of antiretroviral therapy (ART) in low and middle-income countries is a chronic disease intervention of unprecedented magnitude and is the dominant health systems challenge for high-burden countries, many of which rank among the poorest in the world. Substantial external investment, together with the requirement for service evolution to adapt to changing needs, including the constant shift to earlier ART initiation, makes outcome monitoring and reporting particularly important. However, there is growing concern at the inability of many high-burden countries to report on the outcomes of patients who have been in care for various durations, or even the number of patients in care at a particular point in time. In many instances, countries can only report on the number of patients ever started on ART. Despite paper register systems coming under increasing strain, the evolution from paper directly to complex electronic medical record solutions is not viable in many contexts. Implementing a bridging solution, such as a simple offline electronic version of the paper register, can be a pragmatic alternative. This paper describes and recommends a three-tiered monitoring approach in low- and middle-income countries based on the experience implementing such a system in the Western Cape province of South Africa. A three-tier approach allows Ministries of Health to strategically implement one of the tiers in each facility offering ART services. Each tier produces the same nationally required monthly enrolment and quarterly cohort reports so that outputs from the three tiers can be aggregated into a single database at any level of the health system. The choice of tier is based on context and resources at the time of implementation. As resources and infrastructure improve, more facilities will transition to the next highest and more technologically sophisticated tier. Implementing a three-tier monitoring system at country level for pre-antiretroviral wellness, ART

  14. Acceptability and Feasibility of a Cell Phone Support Intervention for Youth Living with HIV with Nonadherence to Antiretroviral Therapy.

    PubMed

    Belzer, Marvin E; Kolmodin MacDonell, Karen; Clark, Leslie F; Huang, Jennifer; Olson, Johanna; Kahana, Shoshana Y; Naar, Sylvie; Sarr, Moussa; Thornton, Sarah

    2015-06-01

    A pilot randomized clinical trial of youth ages 15-24 nonadherent to antiretroviral therapy (ART) utilizing daily cell phone support was found to have significant improvement in self-reported adherence and HIV RNA. Understanding acceptability and feasibility is critical for future implementation in clinic settings. Exit interviews were obtained from participants and adherence facilitators (AF). Acceptability was assessed from content analysis of exit interviews. Feasibility was assessed via intervention retention and study retention rates. Thirty-seven eligible youth were enrolled with 19 assigned to the intervention. Seven (37%) discontinued the intervention either due to missing over 20% of calls for two consecutive months (N=5) or missing 10 consecutive calls (N=2). Sixteen participants completed exit interviews, 15 reported the call length was just right, 13 reported they would have liked to continue calls after the 24-week intervention, and all participants reported they would recommend the intervention to friends. Scheduling and making calls required less than 1 h per week per participant. Providing cell phone support to youth nonadherent to ART was acceptable and feasible. While the cost is low compared to the price of ART, healthcare systems will need to explore how to cover the cost of providing cell phones (incentive).

  15. Acceptability and Feasibility of a Cell Phone Support Intervention for Youth Living with HIV with Nonadherence to Antiretroviral Therapy.

    PubMed

    Belzer, Marvin E; Kolmodin MacDonell, Karen; Clark, Leslie F; Huang, Jennifer; Olson, Johanna; Kahana, Shoshana Y; Naar, Sylvie; Sarr, Moussa; Thornton, Sarah

    2015-06-01

    A pilot randomized clinical trial of youth ages 15-24 nonadherent to antiretroviral therapy (ART) utilizing daily cell phone support was found to have significant improvement in self-reported adherence and HIV RNA. Understanding acceptability and feasibility is critical for future implementation in clinic settings. Exit interviews were obtained from participants and adherence facilitators (AF). Acceptability was assessed from content analysis of exit interviews. Feasibility was assessed via intervention retention and study retention rates. Thirty-seven eligible youth were enrolled with 19 assigned to the intervention. Seven (37%) discontinued the intervention either due to missing over 20% of calls for two consecutive months (N=5) or missing 10 consecutive calls (N=2). Sixteen participants completed exit interviews, 15 reported the call length was just right, 13 reported they would have liked to continue calls after the 24-week intervention, and all participants reported they would recommend the intervention to friends. Scheduling and making calls required less than 1 h per week per participant. Providing cell phone support to youth nonadherent to ART was acceptable and feasible. While the cost is low compared to the price of ART, healthcare systems will need to explore how to cover the cost of providing cell phones (incentive). PMID:25928772

  16. Mapping Patient–Identified Barriers and Facilitators to Retention in HIV Care and Antiretroviral Therapy Adherence to Andersen's Behavioral Model

    PubMed Central

    Holtzman, Carol W.; Shea, Judy A.; Glanz, Karen; Jacobs, Lisa M.; Gross, Robert; Hines, Janet; Mounzer, Karam; Samuel, Rafik; Metlay, Joshua P.; Yehia, Baligh R.

    2015-01-01

    Andersen's Behavioral Model (ABM) provides a framework for understanding how patient and environmental factors impact health behaviors and outcomes. We compared patient-identified barriers/facilitators to retention in care and antiretroviral therapy (ART) adherence, and evaluated how they mapped to ABM. Qualitative semi-structured interviews with 51 HIV-infected adults at HIV clinics in Philadelphia, PA in 2013 were used to explore patients’ experiences with HIV care and treatment. Interview data were analyzed for themes using a grounded theory approach. Among those interviewed, 53% were male and 88% were non-white; 49% were retained in care, 96% were on ART, and 57% were virally suppressed. Patients discussed 18 barriers/facilitators to retention in care and ART adherence: 11 common to both behaviors (stigma, mental illness, substance abuse, social support, reminder strategies, housing, insurance, symptoms, competing life activities, colocation of services, provider factors), 3 distinct to retention (transportation, clinic experiences, appointment scheduling), and 4 distinct to adherence (medication characteristics, pharmacy services, health literacy, health beliefs). Identified barriers/facilitators mapped to all ABM domains. These data support the use of ABM as a framework for classifying factors influencing HIV-specific health behaviors, and have the potential to inform the design of interventions to improve retention in care and ART adherence. PMID:25671515

  17. Antiretroviral Therapy Normalizes Autoantibody Profile of HIV Patients by Decreasing CD33+CD11b+HLA-DR+ Cells

    PubMed Central

    Meng, Zhefeng; Du, Ling; Hu, Ningjie; Byrd, Daniel; Amet, Tohti; Desai, Mona; Shepherd, Nicole; Lan, Jie; Han, Renzhi; Yu, Qigui

    2016-01-01

    Abstract Autoimmune manifestations are common in human immunodeficiency virus (HIV) patients. However, the autoantibody spectrum associated with HIV infection and the impact of antiretroviral therapy (ART) remains to be determined. The plasma autoantibody spectrum for HIV patients was characterized by protein microarrays containing 83 autoantigens and confirmed by enzyme-linked immunosorbent assay (ELISA). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were analyzed by flow cytometry and their effects on autoantibodies production were determined by B cell ELISpot. Higher levels of autoantibody and higher prevalence of elevated autoantibodies were observed in ART-naive HIV patients compared to healthy subjects and HIV patients on ART. The highest frequency of CD33+CD11b+HLA-DR+ cells was observed in ART-naive HIV patients and was associated with the quantity of elevated autoantibodies. In addition, CD33+CD11b+HLA-DR+ cells other than Tregs or MDSCs boost the B cell response in a dose-dependent manner by in vitro assay. In summary, HIV infection leads to elevation of autoantibodies while ART suppresses the autoimmune manifestation by decreasing CD33+CD11b+HLA-DR+ cells in vivo. The roles of CD33+CD11b+HLA-DR+ cells on disease progression in HIV patients needs further assessment. PMID:27082567

  18. Acceptability and Feasibility of a Cell Phone Support Intervention for Youth Living with HIV with Nonadherence to Antiretroviral Therapy

    PubMed Central

    Kolmodin MacDonell, Karen; Clark, Leslie F.; Huang, Jennifer; Olson, Johanna; Kahana, Shoshana Y.; Naar, Sylvie; Sarr, Moussa; Thornton, Sarah

    2015-01-01

    Abstract A pilot randomized clinical trial of youth ages 15–24 nonadherent to antiretroviral therapy (ART) utilizing daily cell phone support was found to have significant improvement in self-reported adherence and HIV RNA. Understanding acceptability and feasibility is critical for future implementation in clinic settings. Exit interviews were obtained from participants and adherence facilitators (AF). Acceptability was assessed from content analysis of exit interviews. Feasibility was assessed via intervention retention and study retention rates. Thirty-seven eligible youth were enrolled with 19 assigned to the intervention. Seven (37%) discontinued the intervention either due to missing over 20% of calls for two consecutive months (N=5) or missing 10 consecutive calls (N=2). Sixteen participants completed exit interviews, 15 reported the call length was just right, 13 reported they would have liked to continue calls after the 24-week intervention, and all participants reported they would recommend the intervention to friends. Scheduling and making calls required less than 1 h per week per participant. Providing cell phone support to youth nonadherent to ART was acceptable and feasible. While the cost is low compared to the price of ART, healthcare systems will need to explore how to cover the cost of providing cell phones (incentive). PMID:25928772

  19. Immunodeficiency in children starting antiretroviral therapy in low-, middle- and high-income countries

    PubMed Central

    Koller, Manuel; Patel, Kunjal; Chi, Benjamin H.; Wools-Kaloustian, Kara; Dicko, Fatoumata; Chokephaibulkit, Kulkanya; Chimbetete, Cleophas; Avila, Dorita; Hazra, Rohan; Ayaya, Samual; Leroy, Valeriane; Trong, Huu Khanh; Egger, Matthias; Davies, Mary-Ann

    2014-01-01

    Background The CD4 cell count or percent (CD4%) at the start of combination antiretroviral therapy (cART) are important prognostic factors in children starting therapy and an important indicator of program performance. We describe trends and determinants of CD4 measures at cART initiation in children from low-, middle- and high-income countries. Methods We included children aged <16 years from clinics participating in a collaborative study spanning sub-Saharan Africa, Asia, Latin America and the United States of America (USA). Missing CD4 values at cART start were estimated through multiple imputation. Severe immunodeficiency was defined according to World Health Organization criteria. Analyses used generalized additive mixed models adjusted for age, country and calendar year. Results 34,706 children from nine low-income, six lower middle-income, four upper middle-income countries and one high-income country (United States of America, USA) were included; 20,624 children (59%) had severe immunodeficiency. In low-income countries the estimated prevalence of children starting cART with severe immunodeficiency declined from 76% in 2004 to 63% in 2010. Corresponding figures for lower middle-income countries were from 77% to 66% and for upper middle-income countries from 75% to 58%. In the USA, the percentage decreased from 42% to 19% during the period 1996 to 2006. In low- and middle-income countries infants and children aged 12-15 years had the highest prevalence of severe immunodeficiency at cART initiation. Conclusions Despite progress in most low- and middle-income countries, many children continue to start cART with severe immunodeficiency. Early diagnosis and treatment of HIV-infected children to prevent morbidity and mortality associated with immunodeficiency must remain a global public health priority. PMID:25501345

  20. HIV patients' decision of switching to second-line antiretroviral therapy in India.

    PubMed

    de Mello-Sampayo, Felipa

    2015-01-01

    The objective is to examine when patients should switch to second-line antiretroviral therapy (ART) under health uncertainty and in the absence of viral load monitoring. We formalize and solve the therapeutic dilemma about whether or not, and when, to switch a therapy. The model's main value-added consists in the concrete application to patients with HIV in India. In our dynamic stochastic model, health level volatility can be understood as the variation in CD4 count and the trend of health level as increases in CD4 count and, thus, decreases in the incidence of opportunistic infections and mortality. The results of the empirical application suggest that the theoretical model can explain ART treatment switch. Treatment switch depends negatively on the volatility of patients' health, and on trend of health, i.e., the greater the variation in CD4 count and the more CD4 count increase, the fewer treatment switches one expects to occur. Treatment switch also depends negatively on the degree of irreversibility. Under irreversibility, low-risk patients must begin the second-line treatment as soon as possible, which is precisely when the second-line treatment is least valuable. The existence of an option value means that ART first-line regimen may be the better choice when considering lifetime welfare. Conversely, treatment switch depends positively on the discount rate and on the correlation between the patient's health under first- and second-line treatments. This means that treatment switch is likelier to succeed in second-line treatments that are similar to the first-line treatments, implying that a decision-maker should not rely on treatment switch as a risk diversification tool.

  1. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy.

    PubMed

    Palmer, Sarah; Maldarelli, Frank; Wiegand, Ann; Bernstein, Barry; Hanna, George J; Brun, Scott C; Kempf, Dale J; Mellors, John W; Coffin, John M; King, Martin S

    2008-03-11

    Residual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter. Single-copy assay results revealed that 77% of the patient samples had detectable low-level viremia (>/=1 copy per ml), and all patients had at least one sample with detectable viremia. A nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39 weeks and a subsequent phase with no perceptible decay. The level of pretherapy viremia extrapolated for each phase of decay was significantly correlated with total baseline viremia for each patient (R(2) = 0.27, P = 0.001 and R(2) = 0.19, P < 0.005, respectively), supporting a biological link between the extent of overall baseline viral infection and the infection of long-lived reservoirs. These data suggest that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years. PMID:18332425

  2. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy

    PubMed Central

    Palmer, Sarah; Maldarelli, Frank; Wiegand, Ann; Bernstein, Barry; Hanna, George J.; Brun, Scott C.; Kempf, Dale J.; Mellors, John W.; Coffin, John M.; King, Martin S.

    2008-01-01

    Residual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter. Single-copy assay results revealed that 77% of the patient samples had detectable low-level viremia (≥1 copy per ml), and all patients had at least one sample with detectable viremia. A nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39 weeks and a subsequent phase with no perceptible decay. The level of pretherapy viremia extrapolated for each phase of decay was significantly correlated with total baseline viremia for each patient (R2 = 0.27, P = 0.001 and R2 = 0.19, P < 0.005, respectively), supporting a biological link between the extent of overall baseline viral infection and the infection of long-lived reservoirs. These data suggest that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years. PMID:18332425

  3. Metabolic and renal adverse effects of antiretroviral therapy in HIV-infected children and adolescents.

    PubMed

    Fortuny, Clàudia; Deyà-Martínez, Ángela; Chiappini, Elena; Galli, Luisa; de Martino, Maurizio; Noguera-Julian, Antoni

    2015-05-01

    Worldwide, the benefits of combined antiretroviral (ARV) therapy in morbidity and mortality due to perinatally acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to ARV treatment. The other metabolic comorbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit nonsymptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the third and fourth decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts' consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of ARV options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more ARV drugs have proved useful. Specific therapies are also available for some of these comorbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically HIV-infected children and adolescents.

  4. 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.

  5. Directly observed versus self-administered antiretroviral therapies: preference of HIV-positive jailed inmates in San Francisco.

    PubMed

    Saberi, Parya; Caswell, Nikolai H; Jamison, Ross; Estes, Milton; Tulsky, Jacqueline P

    2012-10-01

    Directly observed therapy (DOT) of antiretroviral (ARV) medications has beneficial effects on HIV treatment for incarcerated inmates but has been associated with limited continuation after release and inadvertent disclosure of HIV status. Guided self-administered therapy (g-SAT) may be a preferred method of ARV delivery and may encourage medication-taking behavior. We surveyed the preference of 102 HIV-positive jailed inmates at the San Francisco City and County Jails regarding receiving ARVs via DOT versus g-SAT while incarcerated. Participants overwhelmingly preferred g-SAT over DOT. PMID:22547327

  6. Different delivery models for antiretroviral therapy in sub-Saharan Africa in the context of 'universal access'.

    PubMed

    Harries, Anthony D; Makombe, Simon D; Schouten, Erik J; Ben-Smith, Anne; Jahn, Andreas

    2008-04-01

    In 10 years, in line with the concept of universal access, 25 million HIV-infected patients in sub-Saharan Africa might be on antiretroviral therapy (ART). There are different models of ART delivery, from the individualised, medical approach to the simple, public health approach, both having distinct advantages and disadvantages. This mini-review highlights the essential components of both models and argues that, whatever the mix of different models in a country, both must be underpinned by similar core principles so that uninterrupted drug supplies, patient adherence to therapy and compliance with follow up are assured. Failure to do otherwise is to court disaster.

  7. Dynamic Perturbations of the T-Cell Receptor Repertoire in Chronic HIV Infection and following Antiretroviral Therapy

    PubMed Central

    Heather, James M.; Best, Katharine; Oakes, Theres; Gray, Eleanor R.; Roe, Jennifer K.; Thomas, Niclas; Friedman, Nir; Noursadeghi, Mahdad; Chain, Benjamin

    2016-01-01

    HIV infection profoundly affects many parameters of the immune system and ultimately leads to AIDS, yet which factors are most important for determining resistance, pathology, and response to antiretroviral treatment – and how best to monitor them – remain unclear. We develop a quantitative high-throughput sequencing pipeline to characterize the TCR repertoires of HIV-infected individuals before and after antiretroviral therapy, working from small, unfractionated samples of peripheral blood. This reveals the TCR repertoires of HIV+ individuals to be highly perturbed, with considerably reduced diversity as a small proportion of sequences are highly overrepresented. HIV also causes specific qualitative changes to the repertoire including an altered distribution of V gene usage, depletion of public TCR sequences, and disruption of TCR networks. Short-term antiretroviral therapy has little impact on most of the global damage to repertoire structure, but is accompanied by rapid changes in the abundance of many individual TCR sequences, decreases in abundance of the most common sequences, and decreases in the majority of HIV-associated CDR3 sequences. Thus, high-throughput repertoire sequencing of small blood samples that are easy to take, store, and process can shed light on various aspects of the T-cell immune compartment and stands to offer insights into patient stratification and immune reconstitution. PMID:26793190

  8. Comparative Impact of Suppressive Antiretroviral Regimens on the CD4/CD8 T-Cell Ratio: A Cohort Study.

    PubMed

    Masiá, Mar; Padilla, Sergio; Barber, Xavier; Sanchis, Marina; Terol, Gertrudis; Lidón, Fernando; Gutiérrez, Félix

    2016-03-01

    Although different factors have been implicated in the CD4/CD8 T-cell ratio recovery in HIV-infected patients who receive effective antiretroviral therapy (ART), limited information exists on the influence of the regimen composition. A longitudinal study carried out in a prospective, single-center cohort of HIV-infected patients. ART regimens including non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), or integrase strand transfer inhibitors (INSTI) from patients who achieved long-term (≥6-month duration) virological suppression (HIV-RNA < 400 copies/mL) from January 1998 to June 2014 were analyzed. The impact of ART composition on the changes of the CD4/CD8 T-cell ratio was modeled using a mixed linear approach with adjustment for possible confounders. A total of 1068 ART regimens from 570 patients were analyzed. Mean (SD) age of the patients was 42.15 (10.68) years and 276 (48.42%) had hepatitis C virus (HCV) coinfection. Five hundred fifty-eight (52.25%) regimens were PI-based, 439 (40.10%) NNRTI-based, and 71 (6.65%) INSTI-based; 487 (45.60%) were initial regimens, 476 (44.57%) simplification, and 105 (9.83%) salvage regimens. Median (IQR) number of regimens was 1 (1-2) per patient, of 29 (14-58) months duration, and 4 (3-7) CD4/CD8 measurements per regimen. The median baseline CD4/CD8 ratio was 0.42, 0.50, and 0.54, respectively, with the PI-, NNRTI-, and INSTI-based regimens (P = 0.0073). Overall median (IQR) increase of CD4/CD8 ratio was 0.0245 (-0.0352-0.0690) per year, and a CD4/CD8 ratio ≥1 was achieved in 19.35% of the cases with PI-based, 25.97% with NNRTI-based, and 22.54% with INSTI-based regimens (P = 0.1406). In the adjusted model, the mean CD4/CD8 T-cell ratio increase was higher with NNRTI-based regimens compared for PI-based (estimated coefficient for PI [95% CI], -0.0912 [-0.1604 to -0.0219], P = 0.009). Also, a higher CD4/CD8 baseline ratio was associated with higher CD4/CD8 increase in the

  9. Initiating Antiretroviral Therapy for HIV at a Patient’s First Clinic Visit: The RapIT Randomized Controlled Trial

    PubMed Central

    Rosen, Sydney; Maskew, Mhairi; Fox, Matthew P.; Nyoni, Cynthia; Mongwenyana, Constance; Sanne, Ian; Sauls, Celeste; Long, Lawrence

    2016-01-01

    Background High rates of patient attrition from care between HIV testing and antiretroviral therapy (ART) initiation have been documented in sub-Saharan Africa, contributing to persistently low CD4 cell counts at treatment initiation. One reason for this is that starting ART in many countries is a lengthy and burdensome process, imposing long waits and multiple clinic visits on patients. We estimated the effect on uptake of ART and viral suppression of an accelerated initiation algorithm that allowed treatment-eligible patients to be dispensed their first supply of antiretroviral medications on the day of their first HIV-related clinic visit. Methods and Findings RapIT (Rapid Initiation of Treatment) was an unblinded randomized controlled trial of single-visit ART initiation in two public sector clinics in South Africa, a primary health clinic (PHC) and a hospital-based HIV clinic. Adult (≥18 y old), non-pregnant patients receiving a positive HIV test or first treatment-eligible CD4 count were randomized to standard or rapid initiation. Patients in the rapid-initiation arm of the study (“rapid arm”) received a point-of-care (POC) CD4 count if needed; those who were ART-eligible received a POC tuberculosis (TB) test if symptomatic, POC blood tests, physical exam, education, counseling, and antiretroviral (ARV) dispensing. Patients in the standard-initiation arm of the study (“standard arm”) followed standard clinic procedures (three to five additional clinic visits over 2–4 wk prior to ARV dispensing). Follow up was by record review only. The primary outcome was viral suppression, defined as initiated, retained in care, and suppressed (≤400 copies/ml) within 10 mo of study enrollment. Secondary outcomes included initiation of ART ≤90 d of study enrollment, retention in care, time to ART initiation, patient-level predictors of primary outcomes, prevalence of TB symptoms, and the feasibility and acceptability of the intervention. A survival analysis

  10. Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria

    PubMed Central

    Agbaji, Oche O.; Onu, Adamu; Agaba, Patricia E.; Muazu, Muhammad A.; Falang, Kakjing D.; Idoko, John A.

    2011-01-01

    Background: Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria. Materials and Methods: This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1. Results: Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8±8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively. Conclusions: Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV-infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs. PMID:22083208

  11. Antiretroviral Therapy and Viral Suppression Among Foreign-Born HIV-Infected Persons Receiving Medical Care in the United States

    PubMed Central

    Myers, Tanya R.; Lin, Xia; Skarbinski, Jacek

    2016-01-01

    Abstract Immigrants to the United States are more likely to be diagnosed with human immunodeficiency virus (HIV) infection compared with native-born persons. Navigating access to healthcare in the United States can be challenging for foreign-born persons, and HIV treatment outcomes may be suboptimal for these persons. We compared characteristics of and assessed disparities in clinical outcomes of foreign-born persons in care for HIV in the United States. The Medical Monitoring Project is a complex sample, cross-sectional survey designed to be nationally representative of HIV-infected adults receiving medical care in the United States. Using data from 2009, 2010, and 2011, we conducted descriptive analyses and multivariable logistic regression to assess associations between foreign-born status and antiretroviral therapy (ART) prescription, and between foreign-born status and viral suppression. In all, 13.4% of HIV-infected persons were self-identified as foreign-born; the most common regions of birth were Central America and Mexico (45.4%) and the Caribbean (16.0%). Nearly 90% of foreign-born persons were diagnosed with HIV after entry into the United States. Compared with US-born persons, foreign-born persons were more likely to be younger, Hispanic, less educated, and uninsured. The prevalence of ART prescription (prevalence ratio 1.00; 95% confidence interval 0.98–1.02) was not significantly different between foreign-born and US-born persons. A higher percentage of foreign-born persons achieved viral suppression compared with US-born persons (prevalence ratio 1.05; 95% confidence interval 1.00–1.09). No major disparities in ART prescription and viral suppression were found between foreign-born and US-born HIV-infected persons receiving medical care, despite higher percentages being uninsured. PMID:26986128

  12. Association between age at antiretroviral therapy initiation and 24-month immune response in HIV-infected children in West Africa

    PubMed Central

    Desmonde, Sophie; Dicko, Fatoumata; Koueta, Fla; Eboua, Tanoh; Balestre, Eric; Amani-Bosse, Clarisse; Aka, Edmond A.; Lawson-Evi, Koko; Amorissani-Folquet, Madeleine; Kouakou, Kouadio; Koumakpai, Siriatou; Renner, Lorna; Sy, Haby Signaté; Valériane, Leroy

    2014-01-01

    Objective We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4+ cell response in West African HIV-infected children. Methods All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4+ cell count measurements, including one at ART initiation (baseline) were included. CD4+ cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4+ cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model compared immune recovery for age within 24 months post-ART. Results Of the 4808 children initiated on ART, 3014 were enrol led at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4+ cell gains compared with children less than 2 years, the reference group (P < 0.001). However, by 24 months, we observed higher CD4+cell gain in children who initiated ART between 3 and 4 years compared with those less than 2 years (P < 0.001). The 24-month CD4+ cell gain was also strongest in immunodeficient children at baseline. Among these children, 75% reached immune recovery: 12-month rates were significantly highest in all those aged 2–5 years at ART initiation compared with those less than 2 years. Beyond 12 months on ART, immune recovery was significantly lower in children initiated more than 5 years (adjusted hazard ratio: 0.69, 95% confidence interval: 0.56–0.86). Conclusion These results suggest that both the initiation of ART at the earliest age less than 5 years and before any severe immunodeficiency is needed for improving 24-month immune recovery on ART. PMID:24804858

  13. Effects of 96 Weeks of Rosuvastatin on Bone, Muscle, and Fat in HIV-Infected Adults on Effective Antiretroviral Therapy.

    PubMed

    Erlandson, Kristine M; Jiang, Ying; Debanne, Sara M; McComsey, Grace A

    2016-04-01

    Heightened inflammation and immune activation are associated with lower bone mineral density (BMD) and lean body mass (LBM) among HIV-infected persons. We hypothesized that a reduction in inflammation with rosuvastatin would be associated with improvements in BMD and LBM. HIV-infected participants on stable antiretroviral therapy without statin indication and with heightened immune activation (≥19% CD8(+)CD38(+)HLA-DR(+) T cells) or inflammation (hsCRP ≥2 mg/liter) were randomized to rosuvastatin 10 mg daily or placebo for 96 weeks. Among 72 participants randomized to rosuvastatin and 75 to placebo, there were no significant differences in the relative changes in BMD (p > 0.29) or in fat (p ≥ 0.19). A trend toward increased LBM (p = 0.059) was seen in the rosuvastatin arm without differences in creatinine kinase or self-reported physical activity (p ≥ 0.10). In a multivariable regression model, rosuvastatin was associated with a significant positive effect on LBM after adjusting for age, sex, race, smoking status, and detectable HIV-1 viral load. Higher baseline sCD163 correlated with increases in LBM from weeks 0 to 96 (p = 0.023); greater changes in total and leg lean mass were seen among statin users with higher compared to lower baseline IP-10 levels (LBM 1.8 vs. -0.3%; p = 0.028 and leg lean mass 2.9 vs. -1.7%; p = 0.012). Rosuvastatin is associated with an absence of toxicity on BMD and a potential benefit on LBM over 96 weeks of therapy. The preservation of LBM in the rosuvastatin arm over the 2 years of the study is of major clinical relevance in delaying loss of muscle mass with aging. PMID:26477698

  14. Incomplete Reconstitution of T Cell Subsets on Combination Antiretroviral Therapy in the AIDS Clinical Trials Group Protocol 384

    PubMed Central

    Robbins, Gregory K.; Spritzler, John G.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Rodriguez, Benigno A.; Skowron, Gail; Skolnik, Paul R.; Shafer, Robert W.; Pollard, Richard B.

    2009-01-01

    Background Initiation of combination antiretroviral therapy (ART) results in higher total CD4 cell counts, a surrogate for immune reconstitution. Whether the baseline CD4 cell count affects reconstitution of immune cell subsets has not been well characterized. Methods Using data from 978 patients (621 with comprehensive immunological assessments) from the AIDS [Acquired Immunodeficiency Syndrome] Clinical Trials Group protocol 384, a randomized trial of initial ART, we compared reconstitution of CD4+, CD4+ naive and memory, CD4+ activation, CD8+, CD8+ activation, B, and natural killer cells among patients in different baseline CD4+ strata. Reference ranges for T cell populations in control patients negative for human immunodeficiency virus (HIV) infection were calculated using data from AIDS Clinical Trials Group protocol A5113. Results Patients in the lower baseline CD4+ strata did not achieve total CD4+ cell counts similar to those of patients in the higher strata during 144 weeks of ART, although CD4+ cell count increases were similar. Ratios of CD4+ naive-memory cell counts and CD4+:CD8+ cell counts remained significantly reduced in patients with lower baseline CD4+ cell counts (≤350 cells/mm3). These immune imbalances were most notable for those initiating ART with a baseline CD4+ cell count ≤200 cells/mm3, even after adjustment for baseline plasma HIV RNA levels. Conclusions After nearly 3 years of ART, T cell subsets in patients with baseline CD4+ cell counts >350 cells/mm3 achieved or approached the reference range those of control individuals without HIV infection. In contrast, patients who began ART with ≤350 CD4+ cells/mm3 generally did not regain normal CD4+ naive-memory cell ratios. These results support current guidelines to start ART at a threshold of 350 cells/mm3 and suggest that there may be immunological benefits associated with initiating therapy at even higher CD4+ cell counts. PMID:19123865

  15. Growth patterns reflect response to antiretroviral therapy in HIV-positive infants: potential utility in resource-poor settings.

    PubMed

    Benjamin, D K; Miller, W C; Ryder, R W; Weber, D J; Walter, E; McKinney, R E

    2004-01-01

    Laboratory monitoring of HIV-infected children is the current standard of care in the United States to guide the appropriate use of antiretroviral therapy (ART). Although ART is becoming a reality in some developing countries, laboratory monitoring of ART is costly, necessitating creative approaches to monitoring. As an initial step to guide monitoring of HIV progression in low resource settings, we assessed the utility of the physical examination to predict clinical progression of HIV. We conducted a retrospective cohort study of HIV-infected children using data from Pediatric AIDS Clinical Trials Group Protocol 300. We developed a clinical predictive model, and compared the utility of the clinical model to the change in HIV RNA viral load as diagnostic tests of ART failure. The clinical model incorporated treatment regimen, age, and height velocity: a three-level clinical predictive model provided likelihood ratios of 0.3, 3.9, and 14. For decline in RNA the likelihood ratios were 0.2 (> 1 log decline), 1.4, and 3.5 (> log increase). We developed a simple clinical predictive model that was able to predict clinical progression of HIV after initiation of new ART. The clinical model performed similarly to using changes in HIV RNA viral load. These data should be validated internationally and prospectively, because the test subjects were from a resource rich environment and growth patterns in undernourished children may be impacted differently by HIV and its treatment. The model was most pertinent to children 36 months of age or younger, and was conducted in children receiving monotherapy and dual therapy.

  16. Partner-Focused Adherence Intervention for Second-line Antiretroviral Therapy: A Multinational Randomized Trial (ACTG A5234)

    PubMed Central

    Gross, Robert; Zheng, Lu; La Rosa, Alberto; Sun, Xin; Rosenkranz, Susan L.; Cardoso, Sandra Wagner; Ssali, Francis; Camp, Rob; Godfrey, Catherine; Cohn, Susan E.; Robbins, Gregory K.; Chisada, Anthony; Wallis, Carole L.; Reynolds, Nancy R.; Lu, Darlene; Safren, Steven A.; Hosey, Lara; Severe, Patrice; Collier, Ann C.

    2015-01-01

    Background Adherence is key to antiretroviral therapy (ART) success. Enhanced partner support may benefit patients with prior treatment failure. Methods We conducted a 1:1 randomized trial of a partner-based modified directly observed therapy (mDOT) compared with standard of care (SOC) at 9 sites in 8 countries. Participants had failed a first-line regimen with HIV RNA >1000 copies/mL and a willing partner. Randomization was computer generated and balanced by site. Participants and site investigators were not masked to group assignment. ART included lopinavir/ritonavir (400/100 mg) twice daily and emtricitabine/tenofovir disoproxil fumarate (200/300 mg) once daily. Trained partners observed one ART dose daily ≥5 days/week for 24 weeks. Primary outcome was HIV RNA >400 copies/mL before or at week 48 and adherence measured with microelectronic monitors was a secondary outcome. Findings We randomized 129 participants to mDOT and 128 to SOC, 130 (51%) males, 204 (79%) of African origin, 52 (20%) Latino, with median age 38 years. Partners were parents, 57 (22%), spouses 55 (21%), siblings 50 (19%), friends 41 (16%), and others 54 (21%). Primary outcome occurred in 26% (34/129) of mDOT and 18% (23/128) of SOC participants at week 48 (p=0.13). Median adherence was similar [Q1: 95% vs. 96% p=0.38, Q2: 91% vs. 94% p=0.40, Q3: 90% vs. 93% p=0.17, Q4: 90% vs. 93% p=0.36] in mDOT and SOC, respectively. Interpretation This intervention had no effect on outcomes. Potential reasons include study visits maximizing adherence in both groups and control partners already providing sufficient support. Partner-based training with mDOT does not appear promising to enhance adherence. Intensive follow-up with clinic staff may be a viable strategy in this setting. PMID:25664336

  17. Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation

    PubMed Central

    Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W.; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C.; Currier, Judith S.; Tang, Alice M.; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

    2015-01-01

    Background. Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. Methods. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥10 mg/L) with clinical failure were assessed using multivariable Cox models. Results. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82–14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37–1.58) for anemia without inflammation, and 0.45 (95% CI, .11–1.80) for inflammation without anemia compared to those without anemia and inflammation. Conclusions. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent

  18. Persistently Elevated C-Reactive Protein Level in the First Year of Antiretroviral Therapy, Despite Virologic Suppression, Is Associated With HIV Disease Progression in Resource-Constrained Settings.

    PubMed

    Shivakoti, Rupak; Yang, Wei-Teng; Berendes, Sima; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Santos, Breno; Poongulali, Selvamuthu; Tripathy, Srikanth; Riviere, Cynthia; Lama, Javier R; Cardoso, Sandra W; Sugandhavesa, Patcharaphan; Balagopal, Ashwin; Gupte, Nikhil; Semba, Richard D; Campbell, Thomas B; Bollinger, Robert C; Gupta, Amita

    2016-04-01

    A case-cohort analysis of human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) was performed within a multicountry randomized trial (PEARLS) to assess the prevalence of persistently elevated C-reactive protein (CRP) levels, based on serial measurements of CRP levels, and their association with HIV clinical failure. A persistently elevated CRP level in plasma (defined as ≥ 5 mg/L at both baseline and 24 weeks after ART initiation) was observed in 50 of 205 individuals (24%). A persistently elevated CRP level but not an elevated CRP level only at a single time point was independently associated with increased clinical failure, compared with a persistently low CRP level, despite achievement of virologic suppression. Serial monitoring of CRP levels could identify individuals who are at highest risk of HIV progression and may benefit from future adjunct antiinflammatory therapies. PMID:26621909

  19. Empiric Deworming and CD4 Count Recovery in HIV-Infected Ugandans Initiating Antiretroviral Therapy

    PubMed Central

    Lankowski, Alexander J.; Tsai, Alexander C.; Kanyesigye, Michael; Bwana, Mwebesa; Haberer, Jessica E.; Wenger, Megan; Martin, Jeffrey N.; Bangsberg, David R.; Hunt, Peter W.; Siedner, Mark J.

    2014-01-01

    Background There is conflicting evidence on the immunologic benefit of treating helminth co-infections (“deworming”) in HIV-infected individuals. Several studies have documented reduced viral load and increased CD4 count in antiretroviral therapy (ART) naïve individuals after deworming. However, there are a lack of data on the effect of deworming therapy on CD4 count recovery among HIV-infected persons taking ART. Methodology/Principal Findings To estimate the association between empiric deworming therapy and CD4 count after ART initiation, we performed a retrospective observational study among HIV-infected adults on ART at a publicly operated HIV clinic in southwestern Uganda. Subjects were assigned as having received deworming if prescribed an anti-helminthic agent between 7 and 90 days before a CD4 test. To estimate the association between deworming and CD4 count, we fit multivariable regression models and analyzed predictors of CD4 count, using a time-by-interaction term with receipt or non-receipt of deworming. From 1998 to 2009, 5,379 subjects on ART attended 21,933 clinic visits at which a CD4 count was measured. Subjects received deworming prior to 668 (3%) visits. Overall, deworming was not associated with a significant difference in CD4 count in either the first year on ART (β = 42.8; 95% CI, −2.1 to 87.7) or after the first year of ART (β = −9.9; 95% CI, −24.1 to 4.4). However, in a sub-analysis by gender, during the first year of ART deworming was associated with a significantly greater rise in CD4 count (β = 63.0; 95% CI, 6.0 to 120.1) in females. Conclusions/Significance Empiric deworming of HIV-infected individuals on ART conferred no significant generalized benefit on subsequent CD4 count recovery. A significant association was observed exclusively in females and during the initial year on ART. Our findings are consistent with recent studies that failed to demonstrate an immunologic advantage to empirically deworming ART

  20. Recent trends in early stage response to combination antiretroviral therapy in Australia

    PubMed Central

    McManus, Hamish; Hoy, Jennifer F; Woolley, Ian; Boyd, Mark A; Kelly, Mark D; Mulhall, Brian; Roth, Norman J; Petoumenos, Kathy; Law, Matthew G

    2014-01-01

    Background There have been improvements in combination antiretroviral therapy (cART) over the last 15 years. The aim of this analysis was to assess whether improvements in ART have resulted in improvements in surrogates of HIV outcome. Methods Patients in the Australian HIV Observational Database who initiated treatment using mono/duo therapy prior to 1996, or using cART from 1996 onwards, were included in the analysis. Patients were stratified by era of ART initiation. Median changes in CD4+ and the proportion of patients with detectable HIV viral load (>400 copies/ml) were calculated over the first 4 years of treatment. Probabilities of treatment switch were estimated using the Kaplan-Meier method. Results 2,753 patients were included in the analysis: 28% initiated treatment <1996 using mono/duo therapy; and 72% initiated treatment ≥1996 using cART (30% 1996–99; 12% 2000–03; 11% 2004–07; and 19% ≥2008). Overall CD4 response improved by later era of initiation (p<0.001), although 2000–03 CD4 response was less than that for 1996–99 (p=0.007). The average proportion with detectable viral load from 2 to 4 years post treatment commencement by era was: <1996 mono/duo 0.69 (0.67–0.71); 1996–99 cART 0.29 (0.28–0.30); 2000–03 cART 0.22 (0.20–0.24); 2004–07 cART 0.09 (0.07–0.10); ≥2008 cART 0.04 (0.03–0.05). Probability of treatment switch at 4 years after initiation decreased from 53% in 1996–99 to 29% after 2008 (p<0.001). Conclusions Across the five time-periods examined, there have been incremental improvements for patients initiated on cART, as measured by overall response (viral load and CD4 count), and also increased durability of first-line ART regimens. PMID:24704818

  1. Human Immunodeficiency Virus Replication and Genotypic Resistance in Blood and Lymph Nodes after a Year of Potent Antiretroviral Therapy

    PubMed Central

    Günthard, Huldrych F.; Wong, Joseph K.; Ignacio, Caroline C.; Guatelli, John C.; Riggs, Nanette L.; Havlir, Diane V.; Richman, Douglas D.

    1998-01-01

    Potent antiretroviral therapy can reduce human immunodeficiency virus (HIV) in plasma to levels below the limit of detection for up to 2 years, but the extent to which viral replication is suppressed is unknown. To search for ongoing viral replication in 10 patients on combination antiretroviral therapy for up to 1 year, the emergence of genotypic drug resistance across different compartments was studied and correlated with plasma viral RNA levels. In addition, lymph node (LN) mononuclear cells were assayed for the presence of multiply spliced RNA. Population sequencing of HIV-1 pol was done on plasma RNA, peripheral blood mononuclear cell (PBMC) RNA, PBMC DNA, LN RNA, LN DNA, and RNA from virus isolated from PBMCs or LNs. A special effort was made to obtain sequences from patients with undetectable plasma RNA, emphasizing the rapidly emerging lamivudine-associated M184V mutation. Furthermore, concordance of drug resistance mutations across compartments was investigated. No evidence for viral replication was found in patients with plasma HIV RNA levels of <20 copies/ml. In contrast, evolving genotypic drug resistance or the presence of multiply spliced RNA provided evidence for low-level replication in subjects with plasma HIV RNA levels between 20 and 400 copies/ml. All patients failing therapy showed multiple drug resistance mutations in different compartments, and multiply spliced RNA was present upon examination. Concordance of nucleotide sequences from different tissue compartments obtained concurrently from individual patients was high: 98% in the protease and 94% in the reverse transcriptase regions. These findings argue that HIV replication differs significantly between patients on potent antiretroviral therapy with low but detectable viral loads and those with undetectable viral loads. PMID:9499103

  2. Medication-Taking Practices of Patients on Antiretroviral HIV Therapy: Control, Power, and Intentionality.

    PubMed

    Muessig, Kathryn E; Panter, Abigail T; Mouw, Mary S; Amola, Kemi; Stein, Kathryn E; Murphy, Joseph S; Maiese, Eric M; Wohl, David A

    2015-11-01

    Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) is crucial for health, but patients face numerous challenges achieving sustained lifetime adherence. We conducted six focus groups with 56 PLWH regarding ART adherence barriers and collected sociodemographics and ART histories. Participants were recruited through clinics and AIDS service organizations in North Carolina. Dedoose software was used to support thematic analysis. Participants were 59% male, 77% black, aged 23-67 years, and living with HIV 4-20 years. Discussions reflected the fluid, complex nature of ART adherence. Maintaining adherence required participants to indefinitely assert consistent control across multiple areas including: their HIV disease, their own bodies, health care providers, and social systems (e.g., criminal justice, hospitals, drug assistance programs). Participants described limited control over treatment options, ART's impact on their body, and inconsistent access to ART and subsequent inability to take ART as prescribed. When participants felt they had more decision-making power, intentionally choosing whether and how to take ART was not exclusively a decision about best treating HIV. Instead, through these decisions, participants tried to regain some amount of power and control in their lives. Supportive provider relationships assuaged these struggles, while perceived side-effects and multiple co-morbidities further complicated adherence. Adherence interventions need to better convey adherence as a continuous, changing process, not a fixed state. A perspective shift among care providers could also help address negative consequences of the perceived power struggles and pressures that may drive patients to exert control via intentional medication taking practices.

  3. Dyslipidemias and Elevated Cardiovascular Risk on Lopinavir-Based Antiretroviral Therapy in Cambodia

    PubMed Central

    Ly, Sowath; Ouk, Vara; Chanroeurn, Hak; Thavary, Saem; Boroath, Ban; Canestri, Ana; Viretto, Gérald; Delfraissy, Jean-François; Ségéral, Olivier

    2016-01-01

    Background Lopinavir/ritonavir (LPV/r) is widely used in Cambodia with high efficacy but scarce data exist on long-term metabolic toxicity. Methods We carried out a cross-sectional and retrospective study evaluating metabolic disorders and cardiovascular risk in Cambodian patients on LPV/r-based antiretroviral therapy (ART) for > 1 year followed in Calmette Hospital, Phnom Penh. Data collected included cardiovascular risk factors, fasting blood lipids and glucose, and retrospective collection of bioclinical data. We estimated the 10-year risks of coronary heart disease with the Framingham, Ramathibodi-Electricity Generating Authority of Thailand (Rama-EGAT), and the Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk equations. We identified patients with LDL above targets defined by the French expert group on HIV and by the HIV Medicine Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group (IDSA-AACTG). Results Of 115 patients enrolled—mean age 40.9 years, 69.2% male, mean time on LPV/r 3.8 years—40 (34.8%) had hypercholesterolemia (> 2.40 g/L), and 69 (60.0%) had low HDL cholesterol (< 0.40 g/L). Twelve (10.5%), 28 (24%) and 9 (7.7%) patients had a 10-year risk of coronary heart disease ≥ 10% according to the Framingham, D:A:D, and Rama-EGAT score, respectively. Fifty one (44.4%) and 36 (31.3%) patients had not reached their LDL target according to IDSA-AACTG and French recommendations, respectively. Conclusion Prevalence of dyslipidemia was high in this cohort of HIV-infected Cambodian patients on LPV/r. Roughly one third had high LDL levels requiring specific intervention. PMID:27579612

  4. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

    PubMed

    Sede, Mariano; Parra, Micaela; Manrique, Julieta M; Laufer, Natalia; Jones, Leandro R; Quarleri, Jorge

    2016-09-01

    Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses. PMID:27234841

  5. Time Preferences Predict Mortality among HIV-Infected Adults Receiving Antiretroviral Therapy in Kenya

    PubMed Central

    Thirumurthy, Harsha; Hayashi, Kami; Linnemayr, Sebastian; Vreeman, Rachel C.; Levin, Irwin P.; Bangsberg, David R.; Brewer, Noel T.

    2015-01-01

    Background Identifying characteristics of HIV-infected adults likely to have poor treatment outcomes can be useful for targeting interventions efficiently. Research in economics and psychology suggests that individuals’ intertemporal time preferences, which indicate the extent to which they trade-off immediate vs. future cost and benefits, can influence various health behaviors. While there is empirical support for the association between time preferences and various non-HIV health behaviors and outcomes, the extent to which time preferences predict outcomes of those receiving antiretroviral therapy (ART) has not been examined previously. Methods HIV-infected adults initiating ART were enrolled at a health facility in Kenya. Participants’ time preferences were measured at enrollment and used to classify them as having either a low or high discount rate for future benefits. At 48 weeks, we assessed mortality and ART adherence, as measured by Medication Event Monitoring System (MEMS). Logistic regression models adjusting for socio-economic characteristics and risk factors were used to determine the association between time preferences and mortality as well as MEMS adherence ≥90%. Results Overall, 44% (96/220) of participants were classified as having high discount rates. Participants with high discount rates had significantly higher 48-week mortality than participants with low discount rates (9.3% vs. 3.1%; adjusted odds ratio 3.84; 95% CI 1.03, 14.50). MEMS adherence ≥90% was similar for participants with high vs. low discount rates (42.3% vs. 49.6%, AOR 0.70; 95% CI 0.40, 1.25). Conclusion High discount rates were associated with significantly higher risk of mortality among HIV-infected patients initiating ART. Greater use of time preference measures may improve identification of patients at risk of poor clinical outcomes. More research is needed to further identify mechanisms of action and also to build upon and test the generalizability of this finding

  6. Combined effect of antiretroviral therapy and blockade of IDO in SIV-infected rhesus macaques.

    PubMed

    Boasso, Adriano; Vaccari, Monica; Fuchs, Dietmar; Hardy, Andrew W; Tsai, Wen-Po; Tryniszewska, Elzbieta; Shearer, Gene M; Franchini, Genoveffa

    2009-04-01

    Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-d-tryptophan (d-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). d-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, d-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, d-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-beta mRNA expression in lymph nodes of ART-treated macaques after d-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by d-1mT, which may account for the lack of effect on plasma Kyn. Finally, d-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, d-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which d-1mT inhibited SIV replication in vivo. PMID:19299731

  7. Equity in adherence to antiretroviral therapy among economically vulnerable adolescents living with HIV in Uganda

    PubMed Central

    Bermudez, Laura Gauer; Jennings, Larissa; Ssewamala, Fred M.; Nabunya, Proscovia; Mellins, Claude; McKay, Mary

    2016-01-01

    ABSTRACT Studies from sub-Saharan Africa indicate that children made vulnerable by poverty have been disproportionately affected by HIV with many exposed via mother-to-child transmission. For youth living with HIV, adherence to life-saving treatment regimens are likely to be affected by the complex set of economic and social circumstances that challenge their families and also exacerbate health problems. Using baseline data from the National Institute of Child and Human Development (NICHD) funded Suubi+Adherence study, we examined the extent to which individual and composite measures of equity predict self-reported adherence among Ugandan adolescents aged 10–16 (n = 702) living with HIV. Results showed that greater asset ownership, specifically familial possession of seven or more tangible assets, was associated with greater odds of self-reported adherence (OR 1.69, 95% CI: 1.00–2.85). Our analyses also indicated that distance to the nearest health clinic impacts youth’s adherence to an ARV regimen. Youth who reported living nearest to a clinic were significantly more likely to report optimal adherence (OR 1.49, 95% CI: 0.92–2.40). Moreover, applying the composite equity scores, we found that adolescents with greater economic advantage in ownership of household assets, financial savings, and caregiver employment had higher odds of adherence by a factor of 1.70 (95% CI: 1.07–2.70). These findings suggest that interventions addressing economic and social inequities may be beneficial to increase antiretroviral therapy (ART) uptake among economically vulnerable youth, especially in sub-Saharan Africa. This is one of the first studies to address the question of equity in adherence to ART among economically vulnerable youth with HIV. PMID:27392003

  8. Select Host Restriction Factors Are Associated with HIV Persistence During Antiretroviral Therapy

    PubMed Central

    ABDEL-MOHSEN, Mohamed; WANG, Charlene; STRAIN, Matthew C.; LADA, Steven M.; DENG, Xutao; COCKERHAM, Leslie R.; PILCHER, Christopher D.; HECHT, Frederick M.; LIEGLER, Teri; RICHMAN, Douglas D.; DEEKS, Steven G.; PILLAI, Satish K.

    2015-01-01

    Objective The eradication of HIV necessitates elimination of the HIV latent reservoir. Identifying host determinants governing latency and reservoir size in the setting of antiretroviral therapy (ART) is an important step in developing strategies to cure HIV infection. We sought to determine the impact of cell-intrinsic immunity on the HIV latent reservoir. Design We investigated the relevance of a comprehensive panel of established anti-HIV-1 host restriction factors to multiple established virologic and immunologic measures of viral persistence in HIV-1-infected, ART-suppressed individuals. Methods We measured the mRNA expression of 42 anti-HIV-1 host restriction factors, levels of cell-associated HIV-1 RNA, levels of total pol and 2-LTR circle HIV-1 DNA, and immunophenotypes of CD4+ T cells in 72 HIV-1-infected subjects on suppressive ART (23 subjects initiated ART <1 year post-infection, and 49 subjects initiated ART >1 year post-infection). Correlations were analyzed using non-parametric tests. Results The enhanced expression of a few select host restriction factors, p21, schlafen 11, and PAF1, was strongly associated with reduced CD4+ T cell-associated HIV RNA during ART (p<0.001). In addition, our data suggested that ART perturbs the regulatory relationship between CD4+ T cell activation and restriction factor expression. Lastly, cell-intrinsic immune responses were significantly enhanced in subjects who initiated ART during early versus chronic infection, and may contribute to the reduced reservoir size observed in these individuals. Conclusions Intrinsic immune responses modulate HIV persistence during suppressive ART, and may be manipulated to enhance the efficacy of ART and promote viral eradication through reversal of latency in vivo. PMID:25602681

  9. Discontinuation of Antiretroviral Therapy Among Adults Receiving HIV Care in the United States

    PubMed Central

    Hughes, Alison J.; Mattson, Christine L.; Scheer, Susan; Beer, Linda; Skarbinski, Jacek

    2016-01-01

    Background Continuous antiretroviral therapy (ART) is important for maintaining viral suppression. This analysis estimates prevalence of and reason for ART discontinuation. Methods Three-stage sampling was used to obtain a nationally representative, cross-sectional sample of HIV-infected adults receiving HIV care. Face-to-face interviews and medical record abstractions were collected from June 2009 to May 2010. Data were weighted based on known probabilities of selection and adjusted for nonresponse. Patient characteristics of ART discontinuation, defined as not currently taking ART, stratified by provider-initiated versus non–provider-initiated discontinuation, were examined. Weighted logistic regression models predicted factors associated with ART discontinuation. Results Of adults receiving HIV care in the United States who reported ever initiating ART, 5.6% discontinued treatment. Half of those who discontinued treatment reported provider-initiated discontinuation. Provider-initiated ART discontinuation patients were more likely to have a nadir CD4 ≥200 cells per cubic millimeter. Non–provider-initiated ART discontinuation patients were more likely to have unmet need for supportive services and to have not received HIV care in the past 3 months. Among all patients who discontinued, younger age, female gender, not having continuous health insurance, incarceration, injection drug use, nadir CD4 count ≥200 cells per cubic millimeter, unmet need for supportive services, no care in the past 3 months and HIV diagnosis ≥5 years before interview were independently associated with ART discontinuation. Conclusions These findings inform development of interventions to increase ART persistence by identifying groups at increased risk of ART discontinuation. Evidence-based interventions targeting vulnerable populations are needed and are increasingly important as recent HIV treatment guidelines have recommended universal ART. PMID:24326608

  10. Anti-Retroviral Therapy Increases the Prevalence of Dyslipidemia in South African HIV-Infected Patients

    PubMed Central

    Dave, Joel A.; Levitt, Naomi S.; Ross, Ian L.; Lacerda, Miguel; Maartens, Gary; Blom, Dirk

    2016-01-01

    Purpose Data on the prevalence of dyslipidaemia and associated risk factors in HIV-infected patients from sub-Saharan Africa is sparse. We performed a cross-sectional analysis in a cohort of HIV-infected South African adults. Methods We studied HIV-infected patients who were either antiretroviral therapy (ART)-naive or receiving non-nucleoside reverse transcriptase inhibitor (NNRTI)-based or protease inhibitor (PI)-based ART. Evaluation included fasting lipograms, oral glucose tolerance tests and clinical anthropometry. Dyslipidemia was defined using the NCEP ATPIII guidelines. Results The median age of the participants was 34 years (range 19–68 years) and 78% were women. The prevalence of dyslipidemia in 406 ART-naive and 551 participants on ART was 90.0% and 85%, respectively. Low HDL-cholesterol (HDLC) was the most common abnormality [290/406 (71%) ART-naïve and 237/551 (43%) ART- participants]. Participants on ART had higher triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLC) and HDLC than the ART-naïve group. Severe dyslipidaemia, (LDLC> 4.9 mmol/L or TG >5.0 mmol/L) was present in <5% of participants. In multivariate analyses there were complex associations between age, gender, type and duration of ART and body composition and LDLC, HDLC and TG, which differed between ART-naïve and ART-participants. Conclusion Participants on ART had higher TG, TC, LDLC and HDLC than those who were ART-naïve but severe lipid abnormalities requiring evaluation and treatment were uncommon. PMID:26986065

  11. Harnessing the Prevention Benefits of Antiretroviral Therapy to Address HIV and Tuberculosis

    PubMed Central

    Granich, Reuben; Lo, Ying-Ru; Suthar, Amitabh B; Vitoria, Marco; Baggaley, Rachel; Obermeyer, Carla Makhlouf; McClure, Craig; Souteyrand, Yves; Perriens, Jos; Kahn, James G; Bennett, Rod; Smyth, Caoimhe; Williams, Brian; Montaner, Julio; Hirnschall, Gottfried

    2011-01-01

    After 30 years we are still struggling to address a devastating HIV pandemic in which over 25 million people have died. In 2010, an estimated 34 million people were living with HIV, around 70% of whom live in sub-Saharan Africa. Furthermore, in 2009 there were an estimated 1.2 million new HIV-associated TB cases, and tuberculosis (TB) accounted for 24% of HIV-related deaths. By the end of 2010, 6.6 million people were taking antiretroviral therapy (ART), around 42% of those in need as defined by the 2010 World Health Organization (WHO) guidelines. Despite this achievement, around 9 million people were eligible and still in need of treatment, and new infections (approximately 2.6 million in 2010 alone) continue to add to the future caseload. This combined with the international fiscal crisis has led to a growing concern regarding weakening of the international commitment to universal access and delivery of the Millennium Development Goals by 2015. The recently launched UNAIDS/WHO Treatment 2.0 platform calls for accelerated simplification of ART, in line with a public health approach, to achieve and sustain universal access to ART, including maximizing the HIV and TB preventive benefit of ART by treating people earlier, in line with WHO 2010 normative guidance. The potential individual and public health prevention benefits of using treatment in the prevention of HIV and TB enhance the value of the universal access pledge from a life-saving initiative, to a strategic investment aimed at ending the HIV epidemic. This review analyzes the gaps and summarizes the evidence regarding ART in the prevention of HIV and TB. PMID:21999771

  12. Socioeconomic status and response to antiretroviral therapy in high-income countries: a literature review.

    PubMed

    Burch, Lisa S; Smith, Colette J; Phillips, Andrew N; Johnson, Margaret A; Lampe, Fiona C

    2016-05-15

    It has been shown that socioeconomic factors are associated with the prognosis of several chronic diseases; however, there is no recent systematic review of their effect on HIV treatment outcomes. We aimed to review the evidence regarding the existence of an association of socioeconomic status with virological and immunological response to antiretroviral therapy (ART). We systematically searched the current literature using the database PubMed. We identified and summarized original research studies in high-income countries that assessed the association between socioeconomic factors (education, employment, income/financial status, housing, health insurance, and neighbourhood-level socioeconomic factors) and virological response, immunological response, and ART nonadherence among people with HIV-prescribed ART. A total of 48 studies met the inclusion criteria (26 from the United States, six Canadian, 13 European, and one Australian), of which 14, six, and 35 analysed virological, immunological, and ART nonadherence outcomes, respectively. Ten (71%), four (67%), and 23 (66%) of these studies found a significant association between lower socioeconomic status and poorer response, and none found a significant association with improved response. Several studies showed that adjustment for nonadherence attenuated the association between socioeconomic status and ART response. Our review provides strong support that socioeconomic disadvantage is associated with poorer response to ART. However, most studies have been conducted in settings such as the United States without universal free healthcare access. Further study in settings with free access to ART could help assess the impact of socioeconomic status on ART outcomes and the mechanisms by which it operates. PMID:26919732

  13. Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy.

    PubMed

    Sede, Mariano; Parra, Micaela; Manrique, Julieta M; Laufer, Natalia; Jones, Leandro R; Quarleri, Jorge

    2016-09-01

    Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses.

  14. What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers

    PubMed Central

    Kikuchi, Kimiyo; Poudel, Krishna C; Muganda, John; Sato, Tomoko; Mutabazi, Vincent; Muhayimpundu, Ribakare; Majyambere, Adolphe; Nyonsenga, Simon P; Sase, Eriko; Jimba, Masamine

    2014-01-01

    Introduction Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. Methods We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. Results The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans’ caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Conclusions Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children. PMID:25477050

  15. Deterrents to HIV-patient initiation of antiretroviral therapy in urban Lusaka, Zambia: a qualitative study.

    PubMed

    Musheke, Maurice; Bond, Virginia; Merten, Sonja

    2013-04-01

    Some people living with HIV (PLHIV) refuse to initiate antiretroviral therapy (ART) despite availability. Between March 2010 and September 2011, using a social ecological framework, we investigated barriers to ART initiation in Lusaka, Zambia. In-depth interviews were conducted with PLHIV who were offered treatment but declined (n=37), ART staff (n=5), faith healers (n=5), herbal medicine providers (n=5), and home-based care providers (n=5). One focus group discussion with lay HIV counselors and observations in the community and at an ART clinic were conducted. Interviews were audio-recorded, transcribed, and translated, coded using Atlas ti, and analyzed using latent content analysis. Lack of self-efficacy, negative perceptions of medication, desire for normalcy, and fear of treatment-induced physical body changes, all modulated by feeling healthy, undermined treatment initiation. Social relationships generated and perpetuated these health and treatment beliefs. Long waiting times at ART clinics, concerns about long-term availability of treatment, and taking strong medication amidst livelihood insecurity also dissuaded PLHIV from initiating treatment. PLHIV opted for herbal remedies and faith healing as alternatives to ART, with the former being regarded as effective as ART, while the latter contributed to restoring normalcy through the promise of being healed. Barriers to treatment initiation were not mutually exclusive. Some coalesced to undermine treatment initiation. Ensuring patients initiate ART requires interventions at different levels, addressing, in particular, people's health and treatment beliefs, changing perceptions about effectiveness of herbal remedies and faith healing, improving ART delivery to attenuate social and economic costs and allaying concerns about future non-availability of treatment. PMID:23530573

  16. Trends and Determinants of Antiretroviral Therapy Patient Monitoring Practices in Kenya and Uganda

    PubMed Central

    Dansereau, Emily; Gakidou, Emmanuela; Ng, Marie; Achan, Jane; Burstein, Roy; DeCenso, Brendan; Gasasira, Anne; Ikilezi, Gloria; Kisia, Caroline; Masters, Samuel H.; Njuguna, Pamela; Odeny, Thomas A.; Okiro, Emelda A.; Roberts, D. Allen; Duber, Herbert C.

    2015-01-01

    Introduction Patients receiving antiretroviral therapy (ART) require routine monitoring to track response to treatment and assess for treatment failure. This study aims to identify gaps in monitoring practices in Kenya and Uganda. Methods We conducted a systematic retrospective chart review of adults who initiated ART between 2007 and 2012. We assessed the availability of baseline measurements (CD4 count, weight, and WHO stage) and ongoing CD4 and weight monitoring according to national guidelines in place at the time. Mixed-effects logistic regression models were used to analyze facility and patient factors associated with meeting monitoring guidelines. Results From 2007 to 2012, at least 88% of patients per year in Uganda had a recorded weight at initiation, while in Kenya there was a notable increase from 69% to 90%. Patients with a documented baseline CD4 count increased from 69% to about 80% in both countries. In 2012, 83% and 86% of established patients received the recommended quarterly weight monitoring in Kenya and Uganda, respectively, while semiannual CD4 monitoring was less common (49% in Kenya and 38% in Uganda). Initiating at a more advanced WHO stage was associated with a lower odds of baseline CD4 testing. On-site CD4 analysis capacity was associated with increased odds of CD4 testing at baseline and in the future. Discussion Substantial gaps were noted in ongoing CD4 monitoring of patients on ART. Although guidelines have since changed, limited laboratory capacity is likely to remain a significant issue in monitoring patients on ART, with important implications for ensuring quality care. PMID:26275151

  17. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Vilchez, Regis A.; Keitel, Wendy A.; Visnegarwala, Fehmida; White, Zoe S.; Kozinetz, Claudia A.; Lewis, Dorothy E.; Butel, Janet S.

    2003-01-01

    OBJECTIVE: To assess the frequency of shedding of polyomavirus JC virus (JCV) genotypes in urine of HIV-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: Single samples of urine and blood were collected prospectively from 70 adult HIV-infected patients and 68 uninfected volunteers. Inclusion criteria for HIV-infected patients included an HIV RNA viral load < 1000 copies, CD4 cell count of 200-700 x 106 cells/l, and stable HAART regimen. PCR assays and sequence analysis were carried out using JCV-specific primers against different regions of the virus genome. RESULTS: JCV excretion in urine was more common in HIV-positive patients but not significantly different from that of the HIV-negative group [22/70 (31%) versus 13/68 (19%); P = 0.09]. HIV-positive patients lost the age-related pattern of JCV shedding (P = 0.13) displayed by uninfected subjects (P = 0.01). Among HIV-infected patients significant differences in JCV shedding were related to CD4 cell counts (P = 0.03). Sequence analysis of the JCV regulatory region from both HIV-infected patients and uninfected volunteers revealed all to be JCV archetypal strains. JCV genotypes 1 (36%) and 4 (36%) were the most common among HIV-infected patients, whereas type 2 (77%) was the most frequently detected among HIV-uninfected volunteers. CONCLUSION: These results suggest that JCV shedding is enhanced by modest depressions in immune function during HIV infection. JCV shedding occurred in younger HIV-positive persons than in the healthy controls. As the common types of JCV excreted varied among ethnic groups, JCV genotypes associated with progressive multifocal leukoencephalopathy may reflect demographics of those infected patient populations.

  18. Erectile Dysfunction Among HIV Patients Undergoing Highly Active Antiretroviral Therapy: Dyslipidemia as a Main Risk Factor

    PubMed Central

    Romero-Velez, Gustavo; Lisker-Cervantes, Andrés; Villeda-Sandoval, Christian I; Sotomayor de Zavaleta, Mariano; Olvera-Posada, Daniel; Sierra-Madero, Juan Gerardo; Arreguin-Camacho, Lucrecia O; Castillejos-Molina, Ricardo A

    2014-01-01

    Objective To assess the prevalence and risk factors of erectile dysfunction (ED) in HIV patients from the HIV clinic of a tertiary referral center in Mexico City. Design Prevalence was obtained from cross-sectional studies, and the International Index of Erectile Function (IIEF), a standardized method, was used to assess ED. Methods A cross-sectional study was performed in the HIV clinic. Participants completed the IIEF to allow ED assessment. Information on demographics, clinical and HIV-related variables was retrieved from their medical records. Results One hundred and nine patients were included, with a mean age of 39.9 ± 8.8 years. ED was present in 65.1% of the individuals. Patients had been diagnosed with HIV for a mean of 92.7 ± 70.3 months and had undergone a mean 56.4 ± 45.5 months of HAART. The only variable associated with ED in the univariate analysis was dyslipidemia, and this association was also found in the multivariate analysis (P = 0.01). Conclusions ED is highly prevalent in HIV patients. Dyslipidemia should be considered as a risk factor for ED in HIV patients. Romero-Velez G, Lisker-Cervantes A, Villeda-Sandoval CI, Sotomayor de Zavaleta M, Olvera-Posada D, Sierra-Madero JG, Arreguin-Camacho LO, and Castillejos-Molina RA. Erectile dysfunction among HIV patients undergoing highly active antiretroviral therapy: Dyslipidemia as a main risk factor. Sex Med 2014;2:24–30. PMID:25356298

  19. Pubertal development in HIV-infected African children on first-line antiretroviral therapy

    PubMed Central

    Szubert, Alexander J.; Musiime, Victor; Bwakura-Dangarembizi, Mutsawashe; Nahirya-Ntege, Patricia; Kekitiinwa, Adeodata; Gibb, Diana M.; Nathoo, Kusum; Prendergast, Andrew J.; Walker, A. Sarah

    2015-01-01

    Objectives: To estimate age at attaining Tanner stages in Ugandan/Zimbabwean HIV-infected children initiating antiretroviral therapy (ART) in older childhood and investigate predictors of delayed puberty, particularly age at ART initiation. Design: Observational analysis within a randomized trial. Methods: Tanner staging was assessed every 24 weeks from 10 years of age, menarche every 12 weeks and height every 4–6 weeks. Age at attaining different Tanner stages was estimated using normal interval regression, considering predictors using multivariable regression. Growth was estimated using multilevel models with child-specific intercepts and trajectories. Results: Median age at ART initiation was 9.4 years (inter-quartile range 7.8, 11.3) (n = 582). At the first assessment, the majority (80.2%) were in Tanner stage 1; median follow-up with staging was 2.8 years. There was a strong delaying effect of older age at ART initiation on age at attaining all Tanner stages (P < 0.05) and menarche (P = 0.02); in boys the delaying effect generally weakened with older age. There were additional significant delays associated with greater impairments in pre-ART height-for-age Z-score (P < 0.05) in both sexes and pre-ART BMI-for-age in girls (P < 0.05). There was no evidence that pre-ART immuno-suppression independently delayed puberty or menarche. However, older children/adolescents had significant growth spurts in intermediate Tanner stages, and were still significantly increasing their height when in Tanner stage 5 (P < 0.01). Conclusion: Delaying ART initiation until older childhood substantially delays pubertal development and menarche, independently of immuno-suppression. This highlights that factors other than CD4+, such as pubertal development, need consideration when making decisions about timing of ART initiation in older children. PMID:25710288

  20. Antiretroviral Therapy and Pregnancy Outcomes in Developing Countries: A Systematic Review

    PubMed Central

    Alemu, Fekadu Mazengia; Yalew, Alemayehu Worku; Fantahun, Mesganaw; Ashu, Eta Ebasi

    2015-01-01

    Background: Despite significant efforts to understand adverse pregnancy outcome in women receiving Antiretroviral Therapy (ART), ART-related adverse birth outcomes are still poorly understood. We systematically review ART-related adverse birth outcomes among HIV-infected pregnant women; we also review the covariates associated with adverse birth outcomes in the aforementioned group. Methods: The main source for our systematic review was electronic bibliographic databases. Databases such as MEDLINE, PubMed, EMBASE and AIDSLINE were searched. Furthermore, search engines such as Google and Google Scholar were specifically searched for gray literature. Methodological quality of available literature was assessed using the Newcastle - Ottawa Quality Assessment Scale & M. Hewitt guideline. We examined a total of 1,124 papers and reviewed the studies using the PICOT criteria which stands for Patient (population), Intervention (or “Exposure”), Comparison, Outcome and Type of study. Finally, 32 methodologically fit studies were retained and included in our review. Results: Frequently observed adverse birth outcomes included low birth weight (LBW), Preterm Birth (PB), Small for Gestational Age (SGA), while still birth and congenital anomalies were infrequent. Type of regimen such as Protease Inhibitor (PI) based regimens and timing of initiation of ART are some of the factors associated with adverse pregnancy outcomes. Covariates principally included malnutrition and other co-morbidities such as malaria and HIV. Conclusions and Public Health Implications: There is growing evidence in published literature suggesting that ART might be causing adverse birth outcomes among pregnant women in developing countries. There is a need to consider regimen types for HIV-infected pregnant women. There is need to design large cohort studies.

  1. Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda.

    PubMed

    Russell, Steve; Martin, Faith; Zalwango, Flavia; Namukwaya, Stella; Nalugya, Ruth; Muhumuza, Richard; Katongole, Joseph; Seeley, Janet

    2016-01-01

    The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resource-limited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': they saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other non-medical aspects of wellbeing for self-management which ART

  2. Incidence of pregnancy following antiretroviral therapy initiation and associated factors in eight West African countries

    PubMed Central

    Burgos-Soto, Juan; Balestre, Eric; Minga, Albert; Ajayi, Samuel; Sawadogo, Adrien; Zannou, Marcel D.; Leroy, Valériane; Ekouevi, Didier K.; Dabis, François; Becquet, Renaud

    2014-01-01

    Introduction This study aimed at estimating the incidence of pregnancy after antiretroviral therapy (ART) initiation in eight West African countries over a 10-year period. Methods A retrospective analysis was conducted within the international database of the IeDEA West Africa Collaboration. All HIV-infected women aged <50 years and starting ART for their own health between 1998 and 2011 were eligible. Pregnancy after ART initiation was the main outcome and was based on clinical reporting. Poisson regression analysis accounting for country heterogeneity was computed to estimate first pregnancy incidence post-ART and to identify its associated factors. Pregnancy incidence rate ratios were adjusted on country, baseline CD4 count and clinical stage, haemoglobin, age, first ART regimen and calendar year. Results Overall 29,425 HIV-infected women aged 33 years in median [Inter Quartile Range: 28–38] contributed for 84,870 women-years of follow-up to this analysis. The crude incidence of first pregnancy (2,304 events) was 2.9 per 100 women-years [95% confidence interval [CI]: 2.7–3.0], the highest rate being reported among women aged 25–29 years: 4.7 per 100 women-years; 95% CI: 4.3–5.1. The overall Kaplan-Meier probability of pregnancy occurrence by the fourth year on ART was 10.9% (95% CI: 10.4–11.4) and as high as 28.4% (95% CI: 26.3–30.6) among women aged 20–29 years at ART initiation. Conclusion The rate of pregnancy occurrence after ART initiation among HIV-infected women living in the West Africa region was high. Family planning services tailored to procreation needs should be provided to all HIV-infected women initiating ART and health consequences carefully monitored in this part of the world. PMID:25216079

  3. Finding Meaning: HIV Self-Management and Wellbeing among People Taking Antiretroviral Therapy in Uganda.

    PubMed

    Russell, Steve; Martin, Faith; Zalwango, Flavia; Namukwaya, Stella; Nalugya, Ruth; Muhumuza, Richard; Katongole, Joseph; Seeley, Janet

    2016-01-01

    The health of people living with HIV (PLWH) and the sustained success of antiretroviral therapy (ART) programmes depends on PLWH's motivation and ability to self-manage the condition over the long term, including adherence to drugs on a daily basis. PLWH's self-management of HIV and their wellbeing are likely to be interrelated. Successful self-management sustains wellbeing, and wellbeing is likely to motivate continued self-management. Detailed research is lacking on PLWH's self-management processes on ART in resource-limited settings. This paper presents findings from a study of PLWH's self-management and wellbeing in Wakiso District, Uganda. Thirty-eight PLWH (20 women, 18 men) were purposefully selected at ART facilities run by the government and by The AIDS Support Organisation in and around Entebbe. Two in-depth interviews were completed with each participant over three or four visits. Many were struggling economically, however the recovery of health and hope on ART had enhanced wellbeing and motivated self-management. The majority were managing their condition well across three broad domains of self-management. First, they had mobilised resources, notably through good relationships with health workers. Advice and counselling had helped them to reconceptualise their condition and situation more positively and see hope for the future, motivating their work to self-manage. Many had also developed a new network of support through contacts they had developed at the ART clinic. Second, they had acquired knowledge and skills to manage their health, a useful framework to manage their condition and to live their life. Third, participants were psychologically adjusting to their condition and their new 'self': they saw HIV as a normal disease, were coping with stigma and had regained self-esteem, and were finding meaning in life. Our study demonstrates the centrality of social relationships and other non-medical aspects of wellbeing for self-management which ART

  4. Loss to Care and Death Before Antiretroviral Therapy in Durban, South Africa

    PubMed Central

    Bassett, Ingrid V.; Wang, Bingxia; Chetty, Senica; Mazibuko, Matilda; Bearnot, Benjamin; Giddy, Janet; Lu, Zhigang; Losina, Elena; Walensky, Rochelle P.; Freedberg, Kenneth A.

    2009-01-01

    Objective To examine the loss to care and mortality rates before starting antiretroviral therapy (ART) among ART eligible HIV-infected patients in Durban, South Africa. Design Retrospective cohort study. Methods We reviewed data from ART eligible adults (≥18 years) at an urban HIV clinic that charges a monthly fee from July to December 2006. ART eligibility was based on CD4 count ≤200 cells per microliter or clinical criteria and a psychosocial assessment. Patients who did not start ART and were lost within 3 months were phoned. Correlates of loss to care were evaluated using logistic regression. Results During the study period, 501 patients registered for ART training. Mean time from initial CD4 count to first ART training was 3.6 months (interquartile range 2.3−3.9 months). Four hundred eight patients (81.4%) were in care and on ART at 3-month follow-up, and 11 (2.2%) were in care but had not initiated ART. Eighty-two ART eligible patients (16.4%) were lost before ART initiation. Of these, 28 (34.1%) had died; two thirds of deaths occurred before or within 2 months after the first ART training. Despite multiple attempts, 32 patients (39%) were unreachable by phone. Lower baseline CD4 counts (≤100 cells/μL) and unemployment were independently associated with being lost. Conclusions Loss to care and death occur frequently before starting ART at an HIV clinic in Durban, South Africa. This delay from CD4 count to ART training, even among those with the lowest CD4 counts, highlights the need for interventions that improve linkage to care and prioritize ART initiation for those with low baseline CD4 counts. PMID:19504725

  5. Who starts antiretroviral therapy in Durban, South Africa?… not everyone who should

    PubMed Central

    Bassett, Ingrid V.; Regan, Susan; Chetty, Senica; Giddy, Janet; Uhler, Lauren M.; Holst, Helga; Ross, Douglas; Katz, Jeffrey N.; Walensky, Rochelle P.; Freedberg, Kenneth A.; Losina, Elena

    2012-01-01

    Objective To evaluate rates of antiretroviral therapy (ART) initiation within 12 months of a new HIV diagnosis in Durban, South Africa. Design Prospective observational cohort. Methods Adults (≥18 years) were enrolled before HIV testing at two outpatient clinics into the South African Test, Identify and Link cohort. Both sites offer comprehensive HIV care. HIV test results, CD4 cell counts, dates of ART initiation and dates of death were collected from medical records and 12-month patient/family interviews were conducted. ART eligibility was defined as a CD4 cell count less than 200 cells/μl within 90 days of HIV diagnosis. The primary endpoint was ART initiation within 12 months for ART-eligible subjects. Results From November 2006 to October 2008, 1474 newly diagnosed HIV-infected outpatients were enrolled, 1012 (69%) of whom underwent CD4 cell count testing within 90 days. The median CD4 cell count was 159 cells/μl (interquartile range 65–299). Of those who underwent CD4 cell count testing, 538 (53%) were ART-eligible. Only 210 (39%) eligible enrollees were known to have initiated ART within 12 months. Among ART-eligible subjects, there were 108 known deaths; 82% occurred before ART initiation or with unknown ART initiation status. Men [rate ratio (RR) 1.3, 95% confidence interval (CI) 1.1–1.5] and subjects without an HIV-infected family member/friend (RR 1.3, 95% CI 1.1–1.7) were more likely not to start ART. Conclusion Less than half of ART-eligible subjects started ART within 12 months. Substantial attrition and mortality follow HIV diagnosis before ART initiation in Durban, South Africa. Major efforts directed towards earlier HIV diagnosis, effective linkage to care and timely ART initiation are urgently needed. PMID:20023438

  6. Rapamycin with Antiretroviral Therapy in AIDS-Associated Kaposi Sarcoma: An AIDS Malignancy Consortium Study

    PubMed Central

    Krown, Susan E.; Roy, Debasmita; Lee, Jeannette Y.; Dezube, Bruce J.; Reid, Erin G.; Venkataramanan, Raman; Han, Kelong; Cesarman, Ethel; Dittmer, Dirk P.

    2011-01-01

    Purpose The mammalian target of rapamycin (mTOR) is activated in Kaposi sarcoma (KS) and its inhibitor, rapamycin, has induced KS regression in transplant-associated KS. This study aimed to evaluate rapamycin's safety and toxicity in HIV-infected individuals with KS receiving antiretroviral therapy (ART), investigate rapamycin interactions with both protease inhibitor (PI)-containing and non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing ART regimens, and assess clinical and biological endpoints including KS response and mTOR-dependent signaling. Methods Seven participants, 4 on PI-based and 3 on NNRTI-based ART, had rapamycin titrated to achieve trough concentrations of 5-10 ng/mL. Patients were monitored for safety and KS response. KS biopsies were evaluated for changes in phospho-Ribosomal S6 protein (pRPS6), and phospho-Akt expression. Interleukin-6 and vascular endothelial growth factor levels, HIV and KS-associated herpesvirus viral loads, and CD4 counts were monitored. Results Despite pharmacokinetic interactions resulting in >200-fold differences in cumulative weekly rapamycin doses between participants on PI-containing and NNRTI-containing regimens, treatment was well tolerated. There were no significant changes in viral loads or cytokine levels; modest initial decreases in CD4 counts occurred in some patients. Three participants, all on PI-containing regimens and with higher rapamycin exposure, showed partial KS responses. Three of four subjects whose biopsies were studied at ≥day 50 showed decreased pRPS6 staining. Conclusions Rapamycin appears safe in HIV-infected individuals with KS and can, in some cases, induce tumor regression and affect its molecular targets. Significant pharmacokinetic interactions require careful titration to achieve target drug trough concentrations, but may be exploited to achieve therapeutic benefit. PMID:22067664

  7. Violence and the perceived risks of taking antiretroviral therapy in US jails and prisons

    PubMed Central

    Culbert, Gabriel J.

    2014-01-01

    Purpose About one in five men living with HIV in the USA passes through a correctional center annually. Jails and prisons are seen therefore as key intervention sites to promote HIV treatment as prevention. Almost no research, however, has examined inmates' perspectives on HIV treatment or their strategies for retaining access to antiretroviral therapy (ART) during incarceration. The purpose of this paper is to describe the results of an exploratory study examining men's perceptions of and experiences with HIV care and ART during incarceration. Design/methodology/approach Semi-structured, in-depth interviews were conducted with 42 HIV positive male and male-to-female transgendered persons recently released from male correctional centers in Illinois, USA. Findings Interpersonal violence, a lack of safety, and perceived threats to privacy were frequently cited barriers to one's willingness and ability to access and adhere to treatment. Over 60 percent of study participants reported missed doses or sustained treatment interruption (greater than two weeks) because of failure to disclose their HIV status, delayed prescribing, intermittent dosing and out-of-stock medications, confiscation of medications, and medication strikes. Research limitations/implications Substantial improvements in ART access and adherence are likely to follow organizational changes that make incarcerated men feel safer, facilitate HIV status disclosure, and better protect the confidentiality of inmates receiving ART. Originality/value This study identified novel causes of ART non-adherence among prisoners and provides first-hand information about how violence, stigma, and the pursuit of social support influence prisoner's decisions to disclose their HIV status or accept ART during incarceration. PMID:25764073

  8. Survival benefits of antiretroviral therapy in Brazil: a model-based analysis

    PubMed Central

    Luz, Paula M; Girouard, Michael P; Grinsztejn, Beatriz; Freedberg, Kenneth A; Veloso, Valdilea G; Losina, Elena; Struchiner, Claudio J; MacLean, Rachel L; Parker, Robert A; Paltiel, A David; Walensky, Rochelle P

    2016-01-01

    Objective In Brazil, universal provision of antiretroviral therapy (ART) has been guaranteed free of charge to eligible HIV-positive patients since December 1996. We sought to quantify the survival benefits of ART attributable to this programme. Methods We used a previously published microsimulation model of HIV disease and treatment (CEPAC-International) and data from Brazil to estimate life expectancy increase for HIV-positive patients initiating ART in Brazil. We divided the period of 1997 to 2014 into six eras reflecting increased drug regimen efficacy, regimen availability and era-specific mean CD4 count at ART initiation. Patients were simulated first without ART and then with ART. The 2014-censored and lifetime survival benefits attributable to ART in each era were calculated as the product of the number of patients initiating ART in a given era and the increase in life expectancy attributable to ART in that era. Results In total, we estimated that 598,741 individuals initiated ART. Projected life expectancy increased from 2.7, 3.3, 4.1, 4.9, 5.5 and 7.1 years without ART to 11.0, 17.5, 20.7, 23.0, 25.3, and 27.0 years with ART in Eras 1 through 6, respectively. Of the total projected lifetime survival benefit of 9.3 million life-years, 16% (or 1.5 million life-years) has been realized as of December 2014. Conclusions Provision of ART through a national programme has led to dramatic survival benefits in Brazil, the majority of which are still to be realized. Improvements in initial and subsequent ART regimens and higher CD4 counts at ART initiation have contributed to these increasing benefits. PMID:27029828

  9. Equity in adherence to antiretroviral therapy among economically vulnerable adolescents living with HIV in Uganda.

    PubMed

    Bermudez, Laura Gauer; Jennings, Larissa; Ssewamala, Fred M; Nabunya, Proscovia; Mellins, Claude; McKay, Mary

    2016-03-01

    Studies from sub-Saharan Africa indicate that children made vulnerable by poverty have been disproportionately affected by HIV with many exposed via mother-to-child transmission. For youth living with HIV, adherence to life-saving treatment regimens are likely to be affected by the complex set of economic and social circumstances that challenge their families and also exacerbate health problems. Using baseline data from the National Institute of Child and Human Development (NICHD) funded Suubi+Adherence study, we examined the extent to which individual and composite measures of equity predict self-reported adherence among Ugandan adolescents aged 10-16 (n = 702) living with HIV. Results showed that greater asset ownership, specifically familial possession of seven or more tangible assets, was associated with greater odds of self-reported adherence (OR 1.69, 95% CI: 1.00-2.85). Our analyses also indicated that distance to the nearest health clinic impacts youth's adherence to an ARV regimen. Youth who reported living nearest to a clinic were significantly more likely to report optimal adherence (OR 1.49, 95% CI: 0.92-2.40). Moreover, applying the composite equity scores, we found that adolescents with greater economic advantage in ownership of household assets, financial savings, and caregiver employment had higher odds of adherence by a factor of 1.70 (95% CI: 1.07-2.70). These findings suggest that interventions addressing economic and social inequities may be beneficial to increase antiretroviral therapy (ART) uptake among economically vulnerable youth, especially in sub-Saharan Africa. This is one of the first studies to address the question of equity in adherence to ART among economically vulnerable youth with HIV. PMID:27392003

  10. Viral Decay Kinetics in the Highly Active Antiretroviral Therapy-Treated Rhesus Macaque Model of AIDS

    PubMed Central

    Deere, Jesse D.; Higgins, Joanne; Cannavo, Elda; Villalobos, Andradi; Adamson, Lourdes; Fromentin, Emilie; Schinazi, Raymond F.; Luciw, Paul A.; North, Thomas W.

    2010-01-01

    To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies. Due to the specificity of non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for HIV-1, we have used RT-SHIV, a chimeric virus of simian immunodeficiency virus with RT from HIV-1. This virus is susceptible to NNRTIs and causes an AIDS-like disease in rhesus macaques. In this study, two groups of HAART-treated, RT-SHIV-infected macaques were analyzed to determine viral decay kinetics. In the first group, viral loads were monitored with a standard TaqMan RT-PCR assay with a limit of detection of 50 viral RNA copies per mL. Upon initiation of HAART, viremia decayed in a bi-phasic manner with half-lives of 1.7 and 8.5 days, respectively. A third phase was observed with little further decay. In the second group, the macaques were followed longitudinally with a more sensitive assay utilizing ultracentrifugation to concentrate virus from plasma. Bi-phasic decay of viral RNA was also observed in these animals with half-lives of 1.8 and 5.8 days. Viral loads in these animals during a third phase ranged from 2–58 RNA copies/mL, with little decay over time. The viral decay kinetics observed in these macaques are similar to those reported for HIV-1 infected humans. These results demonstrate that low-level viremia persists in RT-SHIV-infected macaques despite a HAART regimen commonly used in humans. PMID:20668516

  11. Changes in HIV-1 Subtypes B and C Genital Tract RNA in Women and Men After Initiation of Antiretroviral Therapy

    PubMed Central

    Fiscus, Susan A.; Cu-Uvin, Susan; Eshete, Abel Tilahun; Hughes, Michael D.; Bao, Yajing; Hosseinipour, Mina; Grinsztejn, Beatriz; Badal-Faesen, Sharlaa; Dragavon, Joan; Coombs, Robert W.; Braun, Ken; Moran, Laura; Hakim, James; Flanigan, Timothy; Kumarasamy, N.; Campbell, Thomas B.; Klingman, Karin L.; Nair, Apsara; Walawander, Ann; Smeaton, Laura M.; De Gruttola, Victor; Martinez, Ana I.; Swann, Edith; Barnett, Ronald L.; Brizz, Barbara; Delph, Yvette; Gettinger, Nikki; Mitsuyasu, Ronald T.; Eshleman, Susan; Safren, Steven; Andrade, Adriana; Haas, David W.; Amod, Farida; Berthaud, Vladimir; Bollinger, Robert C.; Bryson, Yvonne; Celentano, David; Chilongozi, David; Cohen, Myron; Collier, Ann C.; Currier, Judith Silverstein; Eron, Joseph; Firnhaber, Cynthia; Flexner, Charles; Gallant, Joel E.; Gulick, Roy M.; Hammer, Scott M.; Hoffman, Irving; Kazembe, Peter; Kumwenda, Johnstone; Kumwenda, Newton; Lama, Javier R.; Lawrence, Jody; Maponga, Chiedza; Martinson, Francis; Mayer, Kenneth; Nielsen, Karin; Pendame, Richard B.; Ramratnam, Bharat; Rooney, James F.; Sanchez, Jorge; Sanne, Ian; Schooley, Robert T.; Snowden, Wendy; Solomon, Suniti; Tabet, Steve; Taha, Taha; Uy, Jonathan; van der Horst, Charles; Wanke, Christine; Gormley, Joan; Marcus, Cheryl J.; Putnam, Beverly; Ntshele, Smanga; Loeliger, Edde; Pappa, Keith A.; Webb, Nancy; Shugarts, David L.; Winters, Mark A.; Descallar, Renard S.; Sharma, Jabin; Poongulali, S.; Cardoso, Sandra Wagner; Faria, Deise Lucia; Berendes, Sima; Burke, Kelly; Kanyama, Cecelia; Kayoyo, Virginia; Samaneka, Wadzanai P.; Chisada, Anthony; Santos, Breno; La Rosa, Alberto; Infante, Rosa; Balfour, Henry H.; Mullan, Beth; Kim, Ge-Youl; Klebert, Michael K.; Mildvan, Donna; Revuelta, Manuel; Jan Geiseler, P.; Santos, Bartolo; Daar, Eric S.; Lopez, Ruben; Frarey, Laurie; Currin, David; Haas, David H.; Bailey, Vicki L.; Tebas, Pablo; Zifchak, Larisa; Sha, Beverly E.; Fritsche, Janice M.

    2013-01-01

    Background. Combination antiretroviral therapy (cART) reduces genital tract human immunodeficiency virus type 1 (HIV-1) load and reduces the risk of sexual transmission, but little is known about the efficacy of cART for decreasing genital tract viral load (GTVL) and differences in sex or HIV-1 subtype. Methods. HIV-1 RNA from blood plasma, seminal plasma, or cervical wicks was quantified at baseline and at weeks 48 and 96 after entry in a randomized clinical trial of 3 cART regimens. Results. One hundred fifty-eight men and 170 women from 7 countries were studied (men: 55% subtype B and 45% subtype C; women: 24% subtype B and 76% subtype C). Despite similar baseline CD4+ cell counts and blood plasma viral loads, women with subtype C had the highest GTVL (median, 5.1 log10 copies/mL) compared to women with subtype B and men with subtype C or B (4.0, 4.0, and 3.8 log10 copies/mL, respectively; P < .001). The proportion of participants with a GTVL below the lower limit of quantification (LLQ) at week 48 (90%) and week 96 (90%) was increased compared to baseline (16%; P < .001 at both times). Women were significantly less likely to have GTVL below the LLQ compared to men (84% vs 94% at week 48, P = .006; 84% vs 97% at week 96, P = .002), despite a more sensitive assay for seminal plasma than for cervical wicks. No difference in GTVL response across the 3 cART regimens was detected. Conclusions. The female genital tract may serve as a reservoir of persistent HIV-1 replication during cART and affect the use of cART to prevent sexual and perinatal transmission of HIV-1. PMID:23532477

  12. Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS

    PubMed Central

    Renner, Lorna A; Dicko, Fatoumata; Kouéta, Fla; Malateste, Karen; Gueye, Ramatoulaye D; Aka, Edmond; Eboua, Tanoh K; Azondékon, Alain; Okomo, Uduok; Touré, Pety; Ekouévi, Didier; Leroy, Valeriane

    2013-01-01

    Introduction There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. Methods Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. Results As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was −2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p≤0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ≥1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p≤0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤−3 was a strong predictor associated with a 5.59 times risk of severe

  13. Mortality of the elderly is still exceedingly high at diagnosis of AIDS despite favourable outcomes after highly active antiretroviral therapy in Recife, Brazil.

    PubMed

    Lacerda, H R; Kitner, D

    2008-07-01

    This study aimed to compare the outcome of an elderly group of AIDS patients with that of a younger group and their features at the time of the diagnosis of AIDS. We evaluated 58 patients aged >60 years and 114 aged 20-39 years, followed for 35.3 months. There was an obvious delay in diagnosing the elderly as they had more AIDS-defining diseases at diagnosis and their most frequent opportunistic infection was pulmonary tuberculosis. Mortality at the time of the diagnosis of AIDS was four times higher in the elderly (24.1% versus 6.1%, P < 0.001). However, when comparing only those submitted to highly active antiretroviral therapy, there was a similar frequency of favourable outcomes; 76.9% in the elderly against 83.1% in the young (P = 0.455). Mean CD4 lymphocyte was 438 cells/mm(3) at the end of follow up in the young when compared with 442 cells/mm(3) in the elderly (P = 0.945). The types of antiretroviral schema and the number of antivirals per patient were similar in both groups.

  14. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system.

    PubMed

    Gomes, Maria João; Neves, José das; Sarmento, Bruno

    2014-01-01

    Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood-brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood-brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS.

  15. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy

    PubMed Central

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory’s development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  16. Nanoparticle-based drug delivery to improve the efficacy of antiretroviral therapy in the central nervous system

    PubMed Central

    Gomes, Maria João; Neves, José das; Sarmento, Bruno

    2014-01-01

    Antiretroviral drug therapy plays a cornerstone role in the treatment of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome patients. Despite obvious advances over the past 3 decades, new approaches toward improved management of infected individuals are still required. Drug distribution to the central nervous system (CNS) is required in order to limit and control viral infection, but the presence of natural barrier structures, in particular the blood–brain barrier, strongly limits the perfusion of anti-HIV compounds into this anatomical site. Nanotechnology-based approaches may help providing solutions for antiretroviral drug delivery to the CNS by potentially prolonging systemic drug circulation, increasing the crossing and reducing the efflux of active compounds at the blood–brain barrier, and providing cell/tissue-targeting and intracellular drug delivery. After an initial overview on the basic features of HIV infection of the CNS and barriers to active compound delivery to this anatomical site, this review focuses on recent strategies based on antiretroviral drug-loaded solid nanoparticles and drug nanosuspensions for the potential management of HIV infection of the CNS. PMID:24741312

  17. Magnetic resonance imaging of folic acid-coated magnetite nanoparticles reflects tissue biodistribution of long-acting antiretroviral therapy.

    PubMed

    Li, Tianyuzi; Gendelman, Howard E; Zhang, Gang; Puligujja, Pavan; McMillan, JoEllyn M; Bronich, Tatiana K; Edagwa, Benson; Liu, Xin-Ming; Boska, Michael D

    2015-01-01

    Regimen adherence, systemic toxicities, and limited drug penetrance to viral reservoirs are obstacles limiting the effectiveness of antiretroviral therapy (ART). Our laboratory's development of the monocyte-macrophage-targeted long-acting nanoformulated ART (nanoART) carriage provides a novel opportunity to simplify drug-dosing regimens. Progress has nonetheless been slowed by cumbersome, but required, pharmacokinetic (PK), pharmacodynamics, and biodistribution testing. To this end, we developed a small magnetite ART (SMART) nanoparticle platform to assess antiretroviral drug tissue biodistribution and PK using magnetic resonance imaging (MRI) scans. Herein, we have taken this technique a significant step further by determining nanoART PK with folic acid (FA) decorated magnetite (ultrasmall superparamagnetic iron oxide [USPIO]) particles and by using SMART particles. FA nanoparticles enhanced the entry and particle retention to the reticuloendothelial system over nondecorated polymers after systemic administration into mice. These data were seen by MRI testing and validated by comparison with SMART particles and direct evaluation of tissue drug levels after nanoART. The development of alendronate (ALN)-coated magnetite thus serves as a rapid initial screen for the ability of targeting ligands to enhance nanoparticle-antiretroviral drug biodistribution, underscoring the value of decorated magnetite particles as a theranostic tool for improved drug delivery. PMID:26082630

  18. Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy.

    PubMed

    López-Verdín, Sandra; Andrade-Villanueva, Jaime; Zamora-Perez, Ana Lourdes; Bologna-Molina, Ronell; Cervantes-Cabrera, José Justino; Molina-Frechero, Nelly

    2013-01-01

    Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV), and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow.

  19. Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy

    PubMed Central

    López-Verdín, Sandra; Andrade-Villanueva, Jaime; Zamora-Perez, Ana Lourdes; Bologna-Molina, Ronell; Cervantes-Cabrera, José Justino

    2013-01-01

    Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV), and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow. PMID:24455222

  20. Differences in Salivary Flow Level, Xerostomia, and Flavor Alteration in Mexican HIV Patients Who Did or Did Not Receive Antiretroviral Therapy.

    PubMed

    López-Verdín, Sandra; Andrade-Villanueva, Jaime; Zamora-Perez, Ana Lourdes; Bologna-Molina, Ronell; Cervantes-Cabrera, José Justino; Molina-Frechero, Nelly

    2013-01-01

    Introduction. Objective and subjective alterations related to salivary flow have been reported in patients infected with human immunodeficiency virus (HIV), and these alterations are associated with the introduction of antiretroviral therapy. The aim of the current study was to discern whether these alterations are disease induced or secondary to drug therapy. Objective. The objective was to determine the relationships between low salivary flow, xerostomia, and flavor alterations in HIV patients who did or did not receive antiretroviral therapy. Materials and Methods. In this cross-sectional study, HIV patients were divided into two groups based on whether they had received antiretroviral therapy. Those patients with a previous diagnosis of any salivary gland disease were excluded. A survey was used to assess subjective variables, and colorimetry and salivary flow rates were measured using the Schirmer global test. Results. A total of 293 patients were included. The therapy group showed a significantly lower average salivary flow than did the group without therapy, and we observed that the flow rate tended to decrease after one year of therapy. The results were not conclusive, despite significant differences in xerostomia and flavor alteration between the groups. Conclusion. The study results suggest that antiretroviral therapy can cause cumulative damage that affects the amount of salivary flow. PMID:24455222

  1. Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects.

    PubMed

    Palmer, Clovis S; Anzinger, Joshua J; Zhou, Jingling; Gouillou, Maelenn; Landay, Alan; Jaworowski, Anthony; McCune, Joseph M; Crowe, Suzanne M

    2014-12-01

    Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.

  2. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation.

  3. Mitochondrial compromise in 3-year old patas monkeys exposed in utero to human-equivalent antiretroviral therapies.

    PubMed

    Liu, Yongmin; Shim Park, Eunwoo; Gibbons, Alexander T; Shide, Eric D; Divi, Rao L; Woodward, Ruth A; Poirier, Miriam C

    2016-08-01

    Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother-to-child transmission of human immunodeficiency virus 1 (HIV-1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15-year old human) after exposure of the dams to human-equivalent in utero ARV exposure protocols. Pregnant patas dams (3-5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P < 0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3-year-old patas offspring was ∼50% reduced in AZT/3TC/ABC-exposed patas (P < 0.01), but not in AZT/3TC/NVP-exposed patas. Overall the data show that 3-year-old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526-534, 2016. © 2016 Wiley Periodicals, Inc.

  4. Mitochondrial compromise in 3-year old patas monkeys exposed in utero to human-equivalent antiretroviral therapies.

    PubMed

    Liu, Yongmin; Shim Park, Eunwoo; Gibbons, Alexander T; Shide, Eric D; Divi, Rao L; Woodward, Ruth A; Poirier, Miriam C

    2016-08-01

    Antiretroviral (ARV) drug therapy, given during pregnancy for prevention of mother-to-child transmission of human immunodeficiency virus 1 (HIV-1), induces fetal mitochondrial dysfunction in some children. However, the persistence/reversibility of that dysfunction is unclear. Here we have followed Erythrocebus patas (patas) monkey offspring for up to 3 years of age (similar in development to a 15-year old human) after exposure of the dams to human-equivalent in utero ARV exposure protocols. Pregnant patas dams (3-5/exposure group) were given ARV drug combinations that included zidovudine (AZT)/lamivudine (3TC)/abacavir (ABC), or AZT/3TC/nevirapine (NVP), for the last 10 weeks (50%) of gestation. Infants kept for 1 and 3 years also received drug for the first 6 weeks of life. In offpsring at birth, 1 and 3 years of age mitochondrial morphology, examined by electron microscopy (EM), was compromised compared to the unexposed controls. Mitochondrial DNA (mtDNA), measured by hybrid capture chemiluminescence assay (HCCA) was depleted in hearts of patas exposed to AZT/3TC/NVP at all ages (P < 0.05), but not in those exposed to AZT/3TC/ABC at any age. Compared to unexposed controls, mitochondrial reserve capacity oxygen consumption rate (OCR by Seahorse) in cultured bone marrow mesenchymal fibroblasts from 3-year-old patas offspring was ∼50% reduced in AZT/3TC/ABC-exposed patas (P < 0.01), but not in AZT/3TC/NVP-exposed patas. Overall the data show that 3-year-old patas sustain persistent mitochondrial dysfunction as a result of perinatal ARV drug exposure. Environ. Mol. Mutagen. 57:526-534, 2016. © 2016 Wiley Periodicals, Inc. PMID:27452341

  5. Insurability of HIV-positive people treated with antiretroviral therapy in Europe: collaborative analysis of HIV cohort studies

    PubMed Central

    Kaulich-Bartz, Josee; Dam, Wayne; May, Margaret T.; Lederberger, Bruno; Widmer, Urs; Phillips, Andrew N.; Grabar, Sophie; Mocroft, Amanda; Vilaro, Josep; van Sighem, Ard; Moreno, Santiago; Dabis, François; Monforte, Antonella D’Arminio; Teira, Ramon; Ingle, Suzanne M.; Sterne, Jonathan A.C.

    2013-01-01

    Objective: To increase equitable access to life insurance for HIV-positive individuals by identifying subgroups with lower relative mortality. Design: Collaborative analysis of cohort studies. Methods: We estimated relative mortality from 6 months after starting antiretroviral therapy (ART), compared with the insured population in each country, among adult patients from European cohorts participating in the ART Cohort Collaboration (ART-CC) who were not infected via injection drug use, had not tested positive for hepatitis C, and started triple ART between 1996–2008. We used Poisson models for mortality, with the expected number of deaths according to age, sex and country specified as offset. Results: There were 1236 deaths recorded among 34 680 patients followed for 174 906 person-years. Relative mortality was lower in patients with higher CD4 cell count and lower HIV-1 RNA 6 months after starting ART, without prior AIDS, who were older, and who started ART after 2000. Compared with insured HIV-negative lives, estimated relative mortality of patients aged 20–39 from France, Italy, United Kingdom, Spain and Switzerland, who started ART after 2000 had 6-month CD4 cell count at least 350 cells/μl and HIV-1 RNA less than104 copies/ml and without prior AIDS was 459%. The proportion of exposure time with relative mortality below 300, 400, 500 and 600% was 28, 43, 61 and 64%, respectively, suggesting that more than 50% of patients (those with lower relative mortality) could be insurable. Conclusion: The continuing long-term effectiveness of ART implies that life insurance with sufficiently long duration to cover a mortgage is feasible for many HIV-positive people successfully treated with ART for more than 6 months. PMID:23449349

  6. Determinants of Viraemia Copy-Years in People with HIV/AIDS Following Initiation of Antiretroviral Therapy

    PubMed Central

    Wright, Stephen T; Hoy, Jennifer; Mulhall, Brian; O’Connor, Catherine C; Petoumenos, Kathy; Read, Timothy; Smith, Don; Woolley, Ian; Boyd, Mark A

    2014-01-01

    Background Recent studies suggest higher cumulative HIV viraemia exposure measured as viraemia copy-years (VCY) is associated with increased all-cause mortality. The objectives of this study are (a) report the association between VCY and all-cause mortality, and (b) assess associations between common patient characteristics and VCY. Methods Analyses were based on patients recruited to the Australian HIV Observational Database (AHOD) who had received ≥ 24 weeks of antiretroviral therapy (ART). We established VCY after 1, 3, 5 and 10 years of ART by calculating the area under the plasma viral load time-series. We used survival methods to determine the association between high VCY and all-cause mortality. We used multivariable mixed-effect models to determine predictors of VCY. We compared a baseline information model with a time-updated model to evaluate discrimination of patients with high VCY. Results Of the 3021 AHOD participants that initiated ART, 2073(69%), 1667(55%), 1267(42%) and 638(21%) were eligible for analysis at 1, 3, 5, 10 years of ART respectively. Multivariable adjusted hazard ratio (HR) association between all-cause mortality and high VCY was statistically significant, HR 1.52(1.09, 2.13), p-value=0.01. Predicting high VCY after one-year of ART for a time-updated model compared to a baseline information only model, the area under the sensitivity/specificity curve (AUC) was 0.92 vs. 0.84; and at 10 years of ART, AUC: 0.87 vs. 0.61 respectively. Conclusion A high cumulative measure of viral load after initiating ART is associated with increased risk of all-cause mortality. Identifying patients with high VCY is improved by incorporating time-updated information. PMID:24463783

  7. Monitoring and Switching of First-line Antiretroviral Therapy in sub-Saharan Africa: Collaborative Analysis of Adult Treatment Cohorts

    PubMed Central

    Haas, Andreas D.; Keiser, Olivia; Balestre, Eric; Brown, Steve; Bissagnene, Emmanuel; Chimbetete, Cleophas; Dabis, François; Davies, Mary-Ann; Hoffmann, Christopher J.; Oyaro, Patrick; Parkes-Ratanshi, Rosalind; Reynolds, Steven J.; Sikazwe, Izukanji; Wools-Kaloustian, Kara; Zannou, Djimon Marcel; Wandeler, Gilles; Egger, Matthias

    2015-01-01

    Background HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004–2013. Methods Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. Findings Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine VL, 1·21 (1·13–1·30) for targeted VL and 0·49 (0·43–0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114–133 cells/µl). Interpretation Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing. PMID:26423252

  8. A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned.

    PubMed

    Collier, Ann C; Chun, Tae-Wook; Maenza, Janine; Coombs, Robert W; Tapia, Kenneth; Chang, Ming; Stevens, Claire E; Justement, J Shawn; Murray, Danielle; Stekler, Joanne D; Mullins, James I; Holte, Sarah E

    2016-01-01

    Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation. PMID:26862469

  9. 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

  10. The use of dried blood spot specimens for HIV-1 drug resistance genotyping in young children initiating antiretroviral therapy

    PubMed Central

    Salimo, Anna T.; Ledwaba, Johanna; Coovadia, Ashraf; Abrams, Elaine J.; Technau, Karl-Günter; Kuhn, Louise; Morris, Lynn; Hunt, Gillian M.

    2015-01-01

    Paired plasma and dried blood spots (DBS) from 232 South African HIV-infected children initiating antiretroviral therapy (ART) were genotyped for drug resistance mutations, most of who had prior exposure to ART for prevention-of-mother-to-child-transmission. Non-nucleoside reverse transcriptase inhibitor mutations were most commonly detected in both specimen types, particularly Y181C/I and K103N/S. Resistance interpretation concordance was achieved in 97% of pairs with 7 children having mutations detected in DBS only. These results validate the preferential use of DBS specimens for HIVDR genotyping in this patient group. PMID:26192603

  11. 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

  12. Effects of a switch from tenofovir- to abacavir-based antiretroviral therapy, with or without atazanavir, on renal function

    PubMed Central

    Guillemi, Silvia A; Ling, Sean H; Dahlby, Julia S; Yip, Benita; Zhang, Wendy; Hull, Mark W; Lima, Viviane Dias; Hogg, Robert S; Werb, Ronald; Montaner, Julio S; Harris, Marianne

    2016-01-01

    Introduction Tenofovir disoproxil fumarate (TDF)–associated renal dysfunction may abate when TDF is replaced with abacavir (ABC). The extent to which the third drug atazanavir contributes to renal dysfunction is unclear. Methods A retrospective analysis was conducted on adults who had plasma viral load (pVL)<200 copies/mL for≥six months while receiving TDF/lamivudine (3TC) – or TDF/emtricitabine (FTC)–based antiretroviral therapy (ART), then switched to ABC/3TC while retaining the third drug in the ART regimen. CD4, pVL, creatinine, estimated glomerular filtration rate (eGFR), serum phosphorus, urine albumin to creatinine ratio and serum lipids were compared between pre-switch baseline and 3, 6 and 12 months after the switch to ABC. Results A total of 286 patients switched from TDF to ABC between 2004 and 2014: 232 (81%) male, median age 48 years (interquartile range (IQR) 42, 56). The third drug was atazanavir (± ritonavir) in 141 (49%) cases. The pVL was<50 copies/mL in 93 to 96% at all time points. Median serum creatinine was 93 µmol/L (IQR 80–111) at baseline and decreased to 88 µmol/L (IQR 78–98) at 12 months after the switch to ABC. Median eGFR increased from 74 (IQR 60–88) mL/min at baseline to 80 mL/min (IQR 69–89) at 12 months. Results were not significantly different between patients on atazanavir versus those on another third drug. Conclusions Viral suppression was maintained among patients who switched from TDF/3TC or TDF/FTC to ABC/3TC. Serum creatinine and eGFR improved up to 12 months after switching to ABC/3TC, irrespective of whether or not patients were also receiving atazanavir±ritonavir. PMID:27624144

  13. Persisting high prevalence of pneumococcal carriage among HIV-infected adults receiving antiretroviral therapy in Malawi: a cohort study

    PubMed Central

    Heinsbroek, Ellen; Tafatatha, Terence; Phiri, Amos; Ngwira, Bagrey; Crampin, Amelia C.; Read, Jonathan M.; French, Neil

    2015-01-01

    Objective: HIV-infected adults have high rates of pneumococcal carriage and invasive disease. We investigated the effect of antiretroviral therapy (ART) on pneumococcal carriage in HIV-infected adults prior to infant pneumococcal conjugate vaccine (PCV) rollout. Design: Observational cohort study. Methods: We recruited HIV-infected adults newly attending a rural HIV clinic in northern Malawi between 2008 and 2010. Nasopharyngeal samples were taken at baseline and after 6, 12, 18 and 24 months. We compared pneumococcal carriage by ART status using generalized estimated equation models adjusted for CD4+ cell count, sex, seasonality, and other potential confounders. Results: In total, 336 individuals were included, of which 223 individuals started ART during follow-up. Individuals receiving ART had higher pneumococcal carriage than individuals not receiving ART (25.9 vs. 19.8%, P = 0.03) particularly for serotypes not included in PCV13 (16.1 vs. 9.6% P = 0.003). Following adjustment, increased carriage of non-PCV13 serotypes was still observed for individuals on ART, but results for all serotypes were nonsignificant [all serotypes: adjusted risk ratio (aRR) 1.22 (0.95–1.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.13–2.62]. Conclusion: Pneumococcal carriage in HIV-infected adults in Malawi remained high despite use of ART, consistent with failure of mucosal immune reconstitution in the upper respiratory tract. There was evidence of increased carriage of non-PCV13 serotypes. HIV-infected adults on ART could remain an important reservoir for pneumococcal diversity post infant pneumococcal vaccine introduction. Control of pneumococcal disease in African HIV remains a priority. PMID:26218599

  14. The influence of partnership on contraceptive use among HIV-infected women accessing antiretroviral therapy in rural Uganda

    PubMed Central

    Nieves, Christina I.; Kaida, Angela; Seage, George R.; Kabakyenga, Jerome; Muyindike, Winnie; Boum, Yap; Mocello, A. Rain; Martin, Jeffrey N.; Hunt, Peter W.; Haberer, Jessica E.; Bangsberg, David R.; Matthews, Lynn T

    2016-01-01

    Objective To determine individual and dyadic factors associated with effective contraceptive use among HIV-infected women accessing antiretroviral therapy (ART) in rural Uganda. Study Design HIV-infected women enrolled in the Uganda AIDS Rural Treatment Outcomes cohort completed questionnaires (detailing socio-behavioral characteristics, sexual and reproductive history, contraceptive use, fertility desires), and phlebotomy (October 2011–March 2013). We describe prevalence of effective contraceptive use (i.e., consistent condom use, and/or oral contraceptives, injectable hormonal contraception, intrauterine device, female sterilization) in the previous six months among sexually active, non-pregnant women (18–40 years). We assessed covariates of contraceptive use using multivariable logistic regression. Results 362 women (median values: age 30 years, CD4 count 397 cells/mm3, 4.0 years since ART initiation) were included. Among 284 sexually active women, 50% did not desire a(nother) child and 51% had a sero-concordant partner. 45% (n=127) reported effective contraceptive use of whom, 57% (n=72) used condoms, 42% (n=53) injectables, 12% (n=15) oral contraceptives, and 11% (n=14) other effective methods. Dual contraception was reported by 6% (n=8). Only ‘partnership fertility desire’ was independently associated with contraceptive use; women who reported neither partner desired a child had significantly increased odds of contraceptive use (aOR: 2.40, 95% CI: 1.07–5.35) compared with women in partnerships where at least one partner desired a child. Conclusions Less than half of sexually active HIV-infected women accessing ART used effective contraception, of which 44% (n=56) relied exclusively on male condoms, highlighting a continued need to expand access to a wider range of longer acting female-controlled contraceptive methods. Association with partnership fertility desire underscores the need to include men in reproductive health programming. PMID:25983013

  15. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

    PubMed Central

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D.; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M.; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L.; Shea, Thomas C.; Liomba, N. George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  16. HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era.

    PubMed

    Evans, Ceri; Humphrey, Jean H; Ntozini, Robert; Prendergast, Andrew J

    2016-01-01

    The ZVITAMBO trial recruited 14,110 mother-infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1-2 years of follow-up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV-unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were >800 cells/μL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and growth failure and determine the impact of ART and cotrimoxazole on outcomes of this vulnerable group of infants in the current era. PMID:27375613

  17. Adherence to Antiretroviral Therapy During and After Pregnancy: Cohort Study on Women Receiving Care in Malawi's Option B+ Program

    PubMed Central

    Haas, Andreas D.; Msukwa, Malango T.; Egger, Matthias; Tenthani, Lyson; Tweya, Hannock; Jahn, Andreas; Gadabu, Oliver J.; Tal, Kali; Salazar-Vizcaya, Luisa; Estill, Janne; Spoerri, Adrian; Phiri, Nozgechi; Chimbwandira, Frank; van Oosterhout, Joep J.; Keiser, Olivia

    2016-01-01

    Background. Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART. Methods. We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days “covered” by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease. Results. Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4–21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center. Conclusions. One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented. PMID:27461920

  18. Mitochondrial Toxicity Studied with the PBMC of Children from the Chinese National Pediatric Highly Active Antiretroviral Therapy Cohort

    PubMed Central

    Liu, Daojie; Yin, Jiming; Qiao, Luxin; Shi, Ying; Dong, Yaowu; Li, Ning; Zhang, Fujie; Chen, Dexi

    2013-01-01

    As the backbone of highly active antiretroviral therapy (HAART), nucleoside reverse transcriptase inhibitors (NRTIs) have effectively improved outcomes for HIV-infected patients. However, long-term treatment with NRTIs can cause a series of pathologies associated with mitochondrial toxicity. To date, the status and mechanism of mitochondrial toxicity induced by NRTIs are still not clear, especially in HIV-infected children. As part of the national pediatric HAART program in China, our study focused on mitochondrial toxicity and its potential mechanism in HIV-1-infected children who were divided into two groups based on their duration of treatment with NRTIs: one group received treatment for less than 36 months and one group was treated for 36 to 72 months. The control group comprised age-matched non-HIV-infected children. Blood lactic acid and ATP levels in peripheral blood mononuclear cells (PBMCs) were measured to evaluate mitochondrial function, and mtDNA copies and mutations in PBMCs were determined for detecting mtDNA lesions. Simultaneously, TK2 and P53R2 gene expression in PBMC was measured. As compared with the control group, blood lactic acid levels in both NRTI treatment groups were significantly higher, whereas ATP levels and mtDNA mutation rates in PBMCs did not differ between the control and the two NRTI treatment groups. Both NRTI treatment groups exhibited significant mtDNA loss. N Moreover, we found that P53R2 mRNA expression and protein levels were significantly reduced in both treatment groups and that TK2 mRNA expression and protein levels were induced in the long-term NRTI treatment group. These results suggest that mitochondrial toxicity occurs in long-term HAART patients and that P53R2 and TK2 levels in PBMCs are useful biomarkers for detecting mitochondrial toxicity in patients on long-term treatment with NRTIs. PMID:23468942

  19. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi.

    PubMed

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L; Shea, Thomas C; Liomba, N George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39-56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥ 2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1-31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61-244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31-57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.

  20. Evaluating the effectiveness of patient education and empowerment to improve patient–provider interactions in antiretroviral therapy clinics in Namibia

    PubMed Central

    Maclachlan, Ellen W.; Shepard-Perry, Mark G.; Ingo, Paulina; Uusiku, James; Mushimba, Ruusa; Simwanza, Ricky; Likoro, Joseph; Brandt, Laura J.; Thomas, Katherine K.; Kasonka, Claude; Hamunime, Ndapewa; O'Malley, Gabrielle

    2016-01-01

    ABSTRACT In order to increase patient active engagement during patient–provider interactions, we developed and implemented patient training sessions in four antiretroviral therapy (ART) clinics in Namibia using a “Patient Empowerment” training curriculum. We examined the impact of these trainings on patient–provider interactions after the intervention. We tested the effectiveness of the intervention using a randomized parallel group design, with half of the 589 enrolled patients randomly assigned to receive the training immediately and the remaining randomized to receive the training 6 months later. The effects of the training on patient engagement during medical consultations were measured at each clinic visit for at least 8 months of follow-up. Each consultation was audiotaped and then coded using the Roter Interaction Analysis System (RIAS). RIAS outcomes were compared between study groups at 6 months. Using intention-to-treat analysis, consultations in the intervention group had significantly higher RIAS scores in doctor facilitation and patient activation (adjusted difference in score 1.19, p = .004), doctor information gathering (adjusted difference in score 2.96, p = .000), patient question asking (adjusted difference in score .48, p = .012), and patient positive affect (adjusted difference in score 2.08, p = .002). Other measures were higher in the intervention group but did not reach statistical significance. We have evidence that increased engagement of patients in clinical consultation can be achieved via a targeted training program, although outcome data were not available on all patients. The patient training program was successfully integrated into ART clinics so that the trainings complemented other services being provided. PMID:26695005

  1. Immune targeting of PD-1{sup hi} expressing cells during and after antiretroviral therapy in SIV-infected rhesus macaques

    SciTech Connect

    Vargas-Inchaustegui, Diego A.; Xiao, Peng; Hogg, Alison E.; Demberg, Thorsten; McKinnon, Katherine; Venzon, David; Brocca-Cofano, Egidio; DiPasquale, Janet; Lee, Eun M.; Hudacik, Lauren; Pal, Ranajit; Sui, Yongjun; Berzofsky, Jay A.; Liu, Linda; Langermann, Solomon; Robert-Guroff, Marjorie

    2013-12-15

    High-level T cell expression of PD-1 during SIV infection is correlated with impaired proliferation and function. We evaluated the phenotype and distribution of T cells and Tregs during antiretroviral therapy plus PD-1 modulation (using a B7-DC-Ig fusion protein) and post-ART. Chronically SIV-infected rhesus macaques received: 11 weeks of ART (Group A); 11 weeks of ART plus B7-DC-Ig (Group B); 11 weeks of ART plus B7-DC-Ig, then 12 weeks of B7-DC-Ig alone (Group C). Continuous B7-DC-Ig treatment (Group C) decreased rebound viremia post-ART compared to pre-ART levels, associated with decreased PD-1{sup hi} expressing T cells and Tregs in PBMCs, and PD-1{sup hi} Tregs in lymph nodes. It transiently decreased expression of Ki67 and α{sub 4}β{sub 7} in PBMC CD4{sup +} and CD8{sup +} Tregs for up to 8 weeks post-ART and maintained Ag-specific T-cell responses at low levels. Continued immune modulation targeting PD-1{sup hi} cells during and post-ART helps maintain lower viremia, keeps a favorable T cell/Treg repertoire and modulates antigen-specific responses. - Highlights: • B7-DC-Ig modulates PD-1{sup hi} cells in SIV-infected rhesus macaques during and post-ART. • Continued PD-1 modulation post-ART maintains PD-1{sup hi} cells at low levels. • Continued PD-1 modulation post-ART maintains a favorable T cell and Treg repertoire.

  2. Before and after the earthquake: a case study of attrition from the HIV antiretroviral therapy program in Haiti

    PubMed Central

    Puttkammer, Nancy H.; Zeliadt, Steven B.; Balan, Jean Gabriel; Baseman, Janet G.; Destiné, Rodney; Domerçant, Jean Wysler; Duvilaire, Jean Marie; Raphael, Nernst Atwood; Sherr, Kenneth; Yuhas, Krista; Barnhart, Scott

    2014-01-01

    Background On January 12, 2010, a devastating 7.0 magnitude earthquake struck the West Department of Haiti, killing more than 200,000 people and injuring or displacing many more. This disaster threatened continuity of HIV care and treatment services. Objectives This case study examined the effect of the devastating 2010 earthquake in Haiti on attrition from the HIV antiretroviral therapy (ART) program. Design The study triangulated retrospective data from existing sources, including: 1) individual-level longitudinal patient data from an electronic medical record for ART patients at two large public sector departmental hospitals differently affected by the earthquake; and 2) aggregate data on the volume of HIV-related services delivered at the two hospitals before and after the earthquake. Methods The study compared ART attrition and service delivery in Jacmel, a site in the ‘very strong’ zone of earthquake impact, and in Jérémie, a site in the ‘light’ zone of earthquake impact. The analysis used time-to-event analysis methods for the individual-level patient data, and descriptive statistical methods for the aggregate service delivery data. Results Adjusted ART attrition risk was lower at the hospital in Jacmel after vs. before the earthquake (HR=0.51; p=0.03), and was lower in Jacmel vs. Jérémie both before (HR=0.55; p=0.01) and after the earthquake (HR=0.35; p=0.001). The number of new ART patient enrollments, new HIV patient registrations, and HIV clinical visits dropped notably in Jacmel immediately after the earthquake, but then rapidly rebounded. On average, there was no change in new ART enrollments per month after vs. before the earthquake at either site. Conclusion These findings underscore the resilience of Haitian ART providers and patients, and contribute evidence that it is possible to maintain continuity of ART services even in the context of a complex humanitarian crisis. PMID:25103146

  3. HIV/antiretroviral therapy-related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma.

    PubMed

    Peraire, J; López-Dupla, M; Alba, V; Beltrán-Debón, R; Martinez, E; Domingo, P; Asensi, V; Leal, M; Viladés, C; Inza, M-I; Escoté, X; Arnedo, M; Mateo, G; Valle-Garay, E; Ferrando-Martinez, S; Veloso, S; Vendrell, J; Gatell, J Ma; Vidal, F

    2015-07-01

    Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.

  4. Correlates of Adherence and Treatment Failure Among Kenyan Patients on Long-term Highly Active Anti-Retroviral Therapy

    PubMed Central

    Ochieng, Washingtone; Kitawi, Rose C.; Nzomo, Timothy J.; Mwatelah, Ruth S.; Kimulwo, Maureen J.; Ochieng, Dorothy J.; Kinyua, Joyceline; Lagat, Nancy; Onyango, Kevin O.; Lwembe, Raphael M.; Mwamburi, Mkaya; Ogutu, Bernhards R.; Oloo, Florence A.; Aman, Rashid

    2015-01-01

    Background Universal access to highly active antiretroviral therapy (HAART) is still elusive in most developing nations. We asked whether peer support influenced adherence and treatment outcome and if a single viral load (VL) could define treatment failure in a resource-limited setting. Methods A multi-center longitudinal and cross-sectional survey of VL, CD4 T-cells and adherence in 546 patients receiving HAART for up to 228 months. VL and CD4 counts were determined using m2000 Abbott RealTime HIV-1 assay and FACS respectively. Adherence was assessed based on pill-count and on self-report. Results Respectively, 55.8%, 22.2% and 22% of the patients had good, fair and poor adherence. Adherence, peer support and regimen but not HIV disclosure, age or gender, independently correlated with VL and durability of treatment in a multivariate analysis (p<0.001). Treatment failure was 35.9% using sequential VL but ranged between 27% and 35% using alternate single VL cross-sectional definitions. More patients failed stavudine (41.2%) than zidovudine (37.4%) or tenofovir (28.8%, P=0.043) treatment arms. Peer support correlated positively with adherence (χ2, p<0.001), with non-adherence highest in the stavudine arm. VL before the time of regimen switch was comparable between patients switching and those not switching treatment. Moreover, 36% of those switching still failed second-line regimen. Conclusion Weak adherence support and inaccessible VL testing threaten to compromise the success of HAART scale-up in Kenya. To hasten ART monitoring and decision-making, we suggest strengthening patient-focused adherence programs, optimizing and aligning regimen to WHO standards, and a single point-of-care VL testing when multiple tests are unavailable. PMID:26009836

  5. A Study of Compliance to Antiretroviral Therapy among HIV Infected Patients at a Tertiary Care Hospital in North Karnataka

    PubMed Central

    Hasabi, Ishwar Siddappa; Kachapur, Chandrashekar; Kaulgud, Ram Suresh

    2016-01-01

    Introduction Compliance to Antiretroviral Therapy (ART) is a primary determinant of treatment success of HIV-AIDS. Many studies have shown inadequate compliance to ART in the Indian population. Aim To assess the compliance to ART among HIV infected patients, to explore the factors affecting compliance and impact of compliance on CD4 count. Materials and Methods A cross-sectional study was conducted with 200 adult patients attending ART center, KIMS, Hubli. The patients were randomly selected and compliance to ART over preceding 3 months was assessed. Reasons for non- compliance were assessed among those with inadequate compliance. Results Mean age of the study population was 40.07±9.99 years. The sex ratio was 1.02:1 (M:F). Majority of patients were in WHO stage 1 with treatment, with CD4 count above 500/μl. Pulmonary tuberculosis was the most common opportunistic infection. Most of the patients were on long term ART, more than 5 years {81 (40.5%)}. Most of the patients were on ZLN regimen {97 (48.5%)}. Compliance over the preceding 3 months was 94.84± 14.93% for ART and 88.97±23.75% for opportunistic infection prophylaxis. There was no significant difference in compliance in relation to age group, sex, educational status, residence, religion, habits, HIV status of spouse or child, the regimen of ART and frequency of dosing. The compliance was better among those on long term treatment, i.e., those on treatment for more than 5 years compared to those who started ART in last 1 year (p=0.06). The most common reasons given by patients for non-compliance were going away from home, busy with other work and simply forgot. Better compliance was associated with higher CD4 count. Conclusion Compliance to ART was inadequate in the studied population, which is a major obstacle to success of ART. PMID:27437267

  6. Evaluating the effectiveness of patient education and empowerment to improve patient-provider interactions in antiretroviral therapy clinics in Namibia.

    PubMed

    Maclachlan, Ellen W; Shepard-Perry, Mark G; Ingo, Paulina; Uusiku, James; Mushimba, Ruusa; Simwanza, Ricky; Likoro, Joseph; Brandt, Laura J; Thomas, Katherine K; Kasonka, Claude; Hamunime, Ndapewa; O'Malley, Gabrielle

    2016-01-01

    In order to increase patient active engagement during patient-provider interactions, we developed and implemented patient training sessions in four antiretroviral therapy (ART) clinics in Namibia using a "Patient Empowerment" training curriculum. We examined the impact of these trainings on patient-provider interactions after the intervention. We tested the effectiveness of the intervention using a randomized parallel group design, with half of the 589 enrolled patients randomly assigned to receive the training immediately and the remaining randomized to receive the training 6 months later. The effects of the training on patient engagement during medical consultations were measured at each clinic visit for at least 8 months of follow-up. Each consultation was audiotaped and then coded using the Roter Interaction Analysis System (RIAS). RIAS outcomes were compared between study groups at 6 months. Using intention-to-treat analysis, consultations in the intervention group had significantly higher RIAS scores in doctor facilitation and patient activation (adjusted difference in score 1.19, p = .004), doctor information gathering (adjusted difference in score 2.96, p = .000), patient question asking (adjusted difference in score .48, p = .012), and patient positive affect (adjusted difference in score 2.08, p = .002). Other measures were higher in the intervention group but did not reach statistical significance. We have evidence that increased engagement of patients in clinical consultation can be achieved via a targeted training program, although outcome data were not available on all patients. The patient training program was successfully integrated into ART clinics so that the trainings complemented other services being provided. PMID:26695005

  7. CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi.

    PubMed

    Gopal, Satish; Fedoriw, Yuri; Kaimila, Bongani; Montgomery, Nathan D; Kasonkanji, Edwards; Moses, Agnes; Nyasosela, Richard; Mzumara, Suzgo; Varela, Carlos; Chikasema, Maria; Makwakwa, Victor; Itimu, Salama; Tomoka, Tamiwe; Kamiza, Steve; Dhungel, Bal M; Chimzimu, Fred; Kampani, Coxcilly; Krysiak, Robert; Richards, Kristy L; Shea, Thomas C; Liomba, N George

    2016-01-01

    There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39-56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥ 2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1-31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61-244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31-57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV. PMID:26934054

  8. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells

    PubMed Central

    Smith, Kellie N.; Mailliard, Robbie B.; Piazza, Paolo A.; Fischer, Will; Korber, Bette T.; Fecek, Ronald J.; Ratner, Deena; Gupta, Phalguni; Mullins, James I.

    2016-01-01

    ABSTRACT Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control. Here we report that naive CD8+ T cells from chronic HIV-1-infected participants on long-term cART can be primed by dendritic cells (DC). These DC must be mature, produce high levels of interleukin 12p70 (IL-12p70), be responsive to CD40 ligand (CD40L), and be loaded with inactivated, autologous HIV-1. These DC-primed CD8+ T cell responders produced high levels of gamma interferon (IFN-γ) in response to a broad range of both conserved and variable regions of Gag and effectively killed CD4+ T cell targets that were either infected with the autologous latent reservoir-associated virus or loaded with autologous Gag peptides. In contrast, HIV-1-specific memory CD8+ T cells stimulated with autologous HIV-1-loaded DC produced IFN-γ in response to a narrow range of conserved and variable Gag peptides compared to the primed T cells and most notably, displayed significantly lower cytolytic function. Our findings highlight the need to selectively induce new HIV-1-specific CTL from naive precursors while avoiding activation of existing, dysfunctional memory T cells in potential curative immunotherapeutic strategies for HIV-1 infection. PMID:27247230

  9. Intensifying Antiretroviral Therapy With Raltegravir and Maraviroc During Early Human Immunodeficiency Virus (HIV) Infection Does Not Accelerate HIV Reservoir Reduction.

    PubMed

    Ostrowski, Mario; Benko, Erika; Yue, Feng Yun; Kim, Connie J; Huibner, Sanja; Lee, Terry; Singer, Joel; Pankovich, Jim; Laeyendecker, Oliver; Kaul, Rupert; Kandel, Gabor; Kovacs, Colin

    2015-12-01

    Background.  Persistent human immunodeficiency virus (HIV) within the CD4(+) T-cell reservoir is an obstacle to eradication. We hypothesized that adding raltegravir and maraviroc to standard combination antiretroviral therapy (cART) during early HIV infection could substantially reduce viral reservoirs as a step towards eradication. Methods.  A prospective, randomized, double-blinded, placebo-controlled pilot trial enrolled 32 participants with documented early (<6 months) HIV infection to either standard cART (emtricitabine/tenofovir/lopinavir/ritonavir) or intensive cART (standard regimen + raltegravir/maraviroc). Human immunodeficiency virus reservoirs were assessed at baseline and at 48 weeks by (1) proviral DNA, (2) cell-associated RNA, and (3) replication-competent virus, all from purified blood CD4(+) T cells, and (4) gut proviral DNA. A multiassay algorithm (MAA) on baseline sera estimated timing of infection. Results.  Thirty individuals completed the study to the 48-week endpoint. The reduction in blood proviral burden was -1.03 log DNA copies/10(6) CD4(+) T cells versus -.84 log in the standard and intensive groups, respectively (P = .056). Overall, there was no significant difference in the rate of decline of HIV-associated RNA, replication-competent virus in blood CD4(+) T cells, nor proviral gut HIV DNA to 48 weeks. Individuals who presented with more recent HIV infection had significantly lower virus reservoirs, and cART tended to reduce their reservoirs to a greater extent. Conclusions.  Intensive cART led to no additional reduction in the blood virus reservoir at 48 weeks compared with standard cART. Human immunodeficiency virus reservoir size is smaller earlier in HIV infection. Other novel treatment strategies in combination with early cART will be needed to eliminate the HIV latent reservoir.

  10. Progression of Liver Fibrosis and Modern Combination Antiretroviral Therapy Regimens in HIV-Hepatitis C–Coinfected Persons

    PubMed Central

    Brunet, Laurence; Moodie, Erica E. M.; Young, Jim; Cox, Joseph; Hull, Mark; Cooper, Curtis; Walmsley, Sharon; Martel-Laferrière, Valérie; Rachlis, Anita; Klein, Marina B.

    2016-01-01

    Background. Liver diseases progress faster in human immunodeficiency virus (HIV)–hepatitis C virus (HCV)-coinfected persons than HIV-monoinfected persons. The aim of this study was to compare rates of liver fibrosis progression (measured by the aspartate-to-platelet ratio index [APRI]) among HIV-HCV–coinfected users of modern protease inhibitor (PI)- and nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens with a backbone of tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC). Methods. Data from a Canadian multicenter cohort study were analyzed, including 315 HCV polymerase chain reaction–positive persons who initiated antiretroviral therapy with a PI or NNRTI and a backbone containing either TDF/FTC or ABC/3TC. Multivariate linear regression analyses with generalized estimating equations were performed after propensity score matching to balance covariates across classes of anchor agent. Results. A backbone of TDF/FTC was received by 67% of PI users and 69% of NNRTI users. Both PI and NNRTI use was associated with increases in APRI over time when paired with a backbone of ABC/3TC: 16% per 5 years (95% confidence interval [CI], 4%, 29%) and 11% per 5 years (95% CI, 2%, 20%), respectively. With TDF/FTC use, no clear association was found among PI users (8% per 5 years, 95% CI, −3%, 19%) or NNRTI users (3% per 5 years, 95% CI, −7%, 12%). Conclusions. Liver fibrosis progression was more influenced by the backbone than by the class of anchor agent in HIV-HCV–coinfected persons. Only ABC/3TC-containing regimens were associated with an increase of APRI score over time, regardless of the class of anchor agent used. PMID:26400998

  11. Prevalence and distribution of the GBV-C/HGV among HIV-1-infected patients under anti-retroviral therapy.

    PubMed

    Alcalde, Rosana; Nishiya, Anna; Casseb, Jorge; Inocêncio, Lilian; Fonseca, Luiz A M; Duarte, Alberto J S

    2010-08-01

    Infection with GB virus C (GBV-C) or hepatitis G virus (HGV) is highly prevalent among HIV/AIDS patients. GBV-C/HGV viremia has not been associated with liver disease and seems to slow HIV disease progression. To study the GBV-C/HGV genotypes prevalence among HIV/AIDS patients and its association with HIV viral load (VL) and CD4+ lymphocyte counts. From February 2003 to February 2004, we analyzed 210 HIV-1-infected subjects who were on anti-retroviral therapy (ART). For 63 of them a PCR-nested to the non-coding 5' (5'NCR) region of the GBV-C/HGV was done, and for 49 a DNA direct sequencing was done. A phylogenetic analysis was performed by PHYLIP program. 63 (30%) of the HIV-1-infected patients were co-infected with GBV-C/HGV. The phylogenetic analysis revealed the following genotypes (and respective relative frequencies): 1 (10%), 2a (41%), 2b (43%), and 3 (6%). Co-infected patients presented lower HIV-1 VL and higher T CD4+ lymphocyte cells counts as compared with patients negative for GBV-C/HGV sequences (log=4.52 vs. 4.71, p=0.036), and T CD4+ lymphocyte counts (cells/mm(3)=322.6 vs. 273.5, p=0.081, respectively). T CD4+ cells counts equal to, or higher than, 200/mm(3) were significantly more common among co-infected patients than among HIV-infected-only patients (p=0.042). The lowest T CD4+ cells counts were associated with genotype 1 and the highest with genotype 2b (p=0.05). The GBV-C/HGV infection prevalence was 30% among HIV-1-infected subjects, and was associated with lower VL and higher CD4+ lymphocyte counts. GBV-C/HGV genotype 2b may be associated with better immunological response. PMID:20420864

  12. HIV-Exposed Uninfected Infants in Zimbabwe: Insights into Health Outcomes in the Pre-Antiretroviral Therapy Era

    PubMed Central

    Evans, Ceri; Humphrey, Jean H.; Ntozini, Robert; Prendergast, Andrew J.

    2016-01-01

    The ZVITAMBO trial recruited 14,110 mother–infant pairs to a randomized controlled trial of vitamin A between 1997 and 2000, before the availability of antiretroviral therapy for HIV prophylaxis or treatment in Zimbabwe. The HIV status of mothers and infants was well characterized through 1–2 years of follow-up, leading to the largest cohort to date of HIV-exposed uninfected (HEU) infants (n = 3135), with a suitable comparison group of HIV-unexposed infants (n = 9510). Here, we draw on 10 years of published findings from the ZVITAMBO trial. HEU infants had increased morbidity compared to HIV-unexposed infants, with 50% more hospitalizations in the neonatal period and 30% more sick clinic visits during infancy, particularly for skin infections, lower respiratory tract infections, and oral thrush. HEU children had 3.9-fold and 2.0-fold higher mortality than HIV-unexposed children during the first and second years of life, respectively, most commonly due to acute respiratory infections, diarrhea/dysentery, malnutrition, sepsis, and meningitis. Infant morbidity and mortality were strongly related to maternal HIV disease severity, and increased morbidity remained until maternal CD4 counts were >800 cells/μL. HEU infants were more likely to be premature and small-for-gestational age than HIV-unexposed infants, and had more postnatal growth failure. Here, we propose a conceptual framework to explain the increased risk of infectious morbidity, mortality, and growth failure among HEU infants, hypothesizing that immune activation and inflammation are key drivers of both infection susceptibility and growth failure. Future studies should further dissect the causes of infection susceptibility and gro