Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery
Cillo AR, Hilldorfer BB, Lalama CM, McKinnon JE, Coombs RW, Tenorio AR, Fox L, Gandhi RT, Ribaudo H, Currier JS, Gulick RM, Wilkin TJ, and Mellors JW. Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery. AIDS 2015; 29(16):2121-2129.
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 (%CD38HLA-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 log10 copies/10 CD4 T-cells). Premaraviroc HIV-1 DNA levels were inversely related to premaraviroc %CD38HLA-DR CD4 T-cells (Spearman = -0.52, P = 0.004), and lower premaraviroc HIV-1 DNA levels were associated with larger decreases in %CD38HLA-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.
Medical Subject Headings
Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cyclohexanes; Female; HIV Infections; HIV-1; Humans; Male; Maraviroc; Middle Aged; Prospective Studies; Treatment Outcome; Triazoles; Viral Load