Virologic and immunologic effects of adding maraviroc to suppressive ART in subjects with suboptimal CD4+ T-cell recovery

Abstract

Background

Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4+ T-cell counts in all subjects. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in subjects with incomplete CD4+ T-cell recovery, we performed a prospective, open-label pilot trial in which maraviroc was added to a suppressive ART regimen for 24 weeks.

Design

A5256 was a single-arm trial in which subjects on suppressive ART with incomplete CD4+ T-cell recovery added maraviroc for 24 weeks.

Methods

We quantified low-level, residual viremia in plasma and total HIV-1 DNA and 2-LTR circles in peripheral blood mononuclear cells before and after maraviroc intensification. We also evaluated markers of CD4+ and CD8+ T-cell immune activation (%CD38+HLA-DR+) and apoptosis (%caspase3+/Bcl-2−).

Results

No effect of maraviroc was found on the probability of detectable plasma viremia (≥1 copy/mL; n=31, exact McNemar p=1.0) or detectable 2-LTR circles (n=28, p=0.25) or on total HIV-1 DNA (n=28, 90% confidence interval: −0.1, +0.3 log ₁₀ copies/10 ⁶ CD4+ T-cells). Pre-maraviroc HIV-1 DNA levels were inversely related to pre-maraviroc %CD38+HLA-DR+ CD4+ T-cells (Spearman=−0.52, p=0.004), and lower pre-maraviroc HIV-1 DNA levels were associated with larger decreases in %CD38+HLA-DR+ CD4+ T-cells during maraviroc intensification (Spearman=0.44, p=0.018).

Conclusions

In subjects on suppressive ART with incomplete CD4+ T-cell recovery, maraviroc intensification did not affect measures of HIV-1 persistence but did decrease persistent CD4+ T-cell immune activation especially in subjects with low pre-intensification levels of HIV-1 DNA.