Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery

Background:Combination antiretroviral therapy (ART) suppresses HIV-1 replication, but does not restore CD4(+) T-cell counts in all individuals. To investigate the effects of maraviroc on HIV-1 persistence and the relations between virologic and immunologic parameters in individuals 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 individuals 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-long terminal repeat (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 (1copy/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). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38(+)HLA-DR+ CD4(+) T-cells (Spearman=-0.52, P=0.004), and lower premaraviroc 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).Conclusion:In individuals 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 individuals with low preintensification levels of HIV-1 DNA.