Background: Effective ART leads to suppression of HIV replication and a consequent increase in CD4 cell count. Differences in CD4 response may exist among newer agents with distinct mechanisms of action.

Methods: We conducted a meta-analysis of recent phase II and III trials in treatment-experienced subjects evaluating newer non-nucleosides (etravirine), protease inhibitors (daruanvir, tipranavir), integrase inhibitors (raltegravir), fusion inhibitors (enfuvirtide), and CCR5 inhibitors (maraviroc, vicriviroc), each in combination with an optimized background regimen. For each arm of each clinical trial, we collected baseline descriptive data, the proportion achieving a plasma HIV-1 RNA <50 copies/mL, and the CD4 cell count increase 24 weeks after the initiation of an optimized antiretroviral regimen. We analyzed predictors of CD4 cell count increase using a linear model with generalized estimating equations. Each clinical trial arm was treated as a data point that was weighted by sample size; empirical standard errors were used to account for multiple results from a single clinical trial.

Results: We included 37 treatment arms in 16 clinical trials, including 9 arms from 4 clinical trials with a CCR5 inhibitor. Use of a CCR5 inhibitor was associated with an additional gain of +32 cells/μL (95%CI 19 to 45) at 24 weeks compared to other regimens without a CCR5 inhibitor. The multivariate model also showed CD4 cell increase was associated with the baseline HIV-1 RNA (+21 cells/μL per 0.5 log₁₀ higher level, [95%CI 6 to 36]) and with the virologic response at week 24 (+11 cells/μL per 10% greater proportion of subjects with HIV-1 RNA suppressed to <50 copies/mL [95%CI [9 to 14]). In this model, CD4 cell increase was not associated with the baseline CD4 cell count, gender, or median age.

Conclusions: Use of a CCR5 inhibitor was associated with an enhanced CD4 cell count response in treatment-experienced patients initiating an optimized antiretroviral regimen compared to other regimens. This effect was independent of the degree of virologic suppression. The durability and clinical significance of this observation remain to be determined, but could be explored in subjects with discordant immunologic and virologic responses to therapy.