The relationship of CCR5 antagonists to CD4+ T-cell gain: a meta-regression of recent clinical trials in treatment-experienced HIV-infected patients.

TitleThe relationship of CCR5 antagonists to CD4+ T-cell gain: a meta-regression of recent clinical trials in treatment-experienced HIV-infected patients.
Publication TypeJournal Article
Year of Publication2010
AuthorsWilkin TJ, Ribaudo HR, Tenorio AR, Gulick RM
JournalHIV Clin Trials
Volume11
Issue6
Pagination351-8
Date Published2010 Nov-Dec
ISSN1528-4336
KeywordsAnti-Retroviral Agents, CCR5 Receptor Antagonists, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, HIV Infections, HIV-1, Humans, Randomized Controlled Trials as Topic, Regression Analysis, Treatment Outcome, Viral Load
Abstract

PURPOSE: Lower CD4+ T-cell counts are related to increased morbidity and mortality despite virologic suppression. CCR5 antagonists are associated with robust CD4+ T-cell responses. We examined the relationship of CCR5 antagonists to CD4+ T-cell gains.

DESIGN: Meta-regression of recent phase 2-3 trials evaluating new antiretroviral agents in treatment-experienced subjects.

METHODS: We analyzed the relationship of CCR5 antagonists to CD4+ T-cell count increase 24 weeks after initiating the new regimen using a linear model with generalized estimating equations controlling for differing rates of virologic suppression. Each treatment group was treated as a data point weighted by sample size.

RESULTS: We included 46 treatment groups from 17 trials (11 groups from 5 trials used CCR5 antagonists). Controlling for average baseline HIV-1 RNA and proportion of subjects achieving HIV-1 RNA <50 copies/mL, use of a CCR5 antagonist was associated with an additional significant CD4+ T-cell gain of +30/μL (95% CI, 19-42) at 24 weeks compared to treatment groups not using a CCR5 antagonist.

CONCLUSIONS: Use of a CCR5 antagonist was associated with an enhanced CD4+ T-cell count response independent of virologic suppression. This observation supports further evaluation of CCR5 antagonists in patients with discordant immunologic and virologic responses to ART.

DOI10.1310/hct1106-351
Alternate JournalHIV Clin Trials
PubMed ID21239363
PubMed Central IDPMC3086540
Grant ListK24 AI-51966 / AI / NIAID NIH HHS / United States
K24 AI051966 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01-AI069471 / AI / NIAID NIH HHS / United States