The Relationship of CCR5 Antagonists to CD4+T-Cell Gain: A Meta-Regression of Recent Clinical Trials in Treatment-Experienced HIV-Infected Patients

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/mu L (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.