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Chemokine (C-C motif) receptor 5 -2459 genotype in patients receiving highly active antiretroviral therapy: race-specific influence on virologic success.

ABSTRACT: In patients receiving highly active antiretroviral therapy (HAART), antiretroviral drug-metabolizing enzyme and transporter gene polymorphisms, as well as chemokine receptor gene polymorphisms, may influence response to treatment.In a North American, treated, adherent human immunodeficiency virus (HIV)-positive cohort (self-identified whites, n = 175; blacks, n = 218), we investigated whether CYP2B6 (516G>T, 983T>C), UGT2B7 (IVS1+985A>G, 802C>T), MDR1 3435C>T, chemokine (C-C motif) receptor 2 (CCR2) 190G>A, and CCR5 (-2459G>A, ?32) polymorphisms influenced the time to achieve virologic success (TVLS).No difference in TVLS was observed between races. In Kaplan-Meier analyses, only 516G>T (log-rank P = .045 for comparison of GG, GT, and TT and P = .02 GG + GT vs TT) and -2459G>A (log-rank P = .04 for GG, GA, and AA and P = .02 for GG + GA vs AA) genotypes were significantly associated with TVLS in black patients but not in white patients. However, in the Cox proportional hazards model that included age, sex, baseline CD4(+) T cell count, and baseline viral load, no significant association was observed between 516G>T and TVLS, whereas the association between -2459G>A and TVLS remained significant even after including CCR2 190G>A as well as all the drug-metabolizing enzyme and transporter genotypes.These findings suggest that CCR5 -2459G>A genotype had a strong, race-specific influence on TVLS in this cohort. Understanding the possible mechanisms underlying this influence requires further studies.

SUBMITTER: Mehlotra RK

PROVIDER: S-EPMC3114473 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Chemokine (C-C motif) receptor 5 -2459 genotype in patients receiving highly active antiretroviral therapy: race-specific influence on virologic success.

Mehlotra Rajeev K RK Cheruvu Vinay K VK Blood Zikursh Melinda J MJ Benish Rebekah L RL Lederman Michael M MM Salata Robert A RA Gripshover Barbara B McComsey Grace A GA Lisgaris Michelle V MV Fulton Scott S Subauste Carlos S CS Jurevic Richard J RJ Guillemette Chantal C Zimmerman Peter A PA Rodriguez Benigno B

The Journal of infectious diseases 20110701 2

<h4>Background</h4>In patients receiving highly active antiretroviral therapy (HAART), antiretroviral drug-metabolizing enzyme and transporter gene polymorphisms, as well as chemokine receptor gene polymorphisms, may influence response to treatment.<h4>Methods</h4>In a North American, treated, adherent human immunodeficiency virus (HIV)-positive cohort (self-identified whites, n = 175; blacks, n = 218), we investigated whether CYP2B6 (516G>T, 983T>C), UGT2B7 (IVS1+985A>G, 802C>T), MDR1 3435C>T, ...[more]

PMID: 21673041

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Project description:INTRODUCTION:Directly observed therapy of highly active antiretroviral therapy (DOT-HAART) is a feasible adherence intervention. Prospective DOT-HAART studies have shown mixed results, and optimal target groups have yet to be defined. We performed a meta-analysis and systematic review to assess the effect of DOT-HAART on adherence and virologic and immunologic response. METHODS:We performed a comprehensive search through August 2009 to identify peer-reviewed controlled studies that involved outpatient DOT-HAART among adults and reported at least 1 outcome assessed in this meta-analysis. Random-effects meta-analyses were performed; differences in effect on virologic suppression were examined using stratified meta-analyses and meta-regression on several study characteristics. RESULTS:Seventeen studies met inclusion criteria. Compared with control groups, DOT-HAART recipients were more likely to achieve an undetectable viral load (random effects risk ratio 1.24, 95% confidence interval (CI): 1.08 to 1.41), a greater increase in CD4 cell count (random effects weighted mean difference 43 cells/microL, 95% CI: 12 to 74 cells/microL), and HAART adherence of > or =95% (random effects risk ratio 1.17, 95% CI: 1.03 to 1.32). Results varied with respect to virologic response. DOT-HAART did not have a significant effect on virologic suppression when restricted to randomized controlled studies. Post-treatment effect was not observed in a limited number of studies. CONCLUSIONS:DOT-HAART had a significant effect on virologic, immunologic, and adherence outcomes, although its efficacy was not supported when restricting analysis to randomized controlled trials. DOT-HAART shows greatest treatment effect when targeting individuals with greater risk of nonadherence and when delivering the intervention that maximizes participant convenience and provides enhanced adherence support. Further investigation is needed to assess the postintervention effect and cost-effectiveness of DOT-HAART.

Project description:Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART) in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1) mortality, 2) virologic failure, and 3) mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127) of participants died, 6% (n = 31) were lost-to-follow-up and 23% (107/472) experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10-year ART outcomes. A low level of formal education does not appear to be a barrier to successful long-term ART.

Project description:BackgroundMinimizing antiretroviral treatment failure is crucial for improving patient health and for maintaining long-term access to care in low-income settings such as eastern Africa. To develop interventions to support adherence, policymakers must understand the extent and scope of treatment failure in their programs. However, estimates of treatment failure in eastern Africa have been variable and inconclusive.ObjectiveThis systematic review and meta-analysis sought to determine the pooled prevalence of immunological failure among adults receiving antiretroviral therapy in eastern Africa.MethodsWe performed a systematic search of the PubMed, Google Scholar, Excerpta Medica Database, and the World Health Organization's Hinari portal (which includes the Scopus, African Index Medicus, and African Journals Online databases) databases. Unpublished studies were also accessed from conference websites and university repositories. We used Stata version 14 for data analysis. The Cochrane Q test and I 2 test statistic were used to test for heterogeneity across the studies. Due to high levels of heterogeneity, a random effects model was used to estimate the pooled prevalence of immunological failure. Begg and Egger tests of the intercept in the random effects model were used to check for publication bias.ResultsAfter removing duplicates, 25 articles remained for assessment and screening. After quality screening, 15 articles were deemed eligible and incorporated into the final analysis. The average pooled estimate of immunological treatment failure prevalence was found to be 21.89% (95% CI, 15.14-28.64). In the subgroup analysis conducted by geographic region, the pooled prevalence of immunological treatment failure in Ethiopia was 15.2% (95% CI, 12.27-18.13) while in Tanzania it was 53.93% (95% CI, 48.14-59.73). Neither the results of Egger test or Begg tests suggested publication bias; however, on visual examination, the funnel plot appeared asymmetric. The large heterogeneity across the studies could be explained by study country.ConclusionImmunological treatment failure among patients receiving antiretroviral therapy in eastern Africa was high, and greater than previously reported. The relatively low rates of treatment failure found in Ethiopia suggest that its health extension program should be studied as a model for improving adherence in the region. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX) © 2021 Elsevier HS Journals, Inc.

Dataset Information

Chemokine (C-C motif) receptor 5 -2459 genotype in patients receiving highly active antiretroviral therapy: race-specific influence on virologic success.

Publications

Chemokine (C-C motif) receptor 5 -2459 genotype in patients receiving highly active antiretroviral therapy: race-specific influence on virologic success.

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