Studies exploring the immunologic effects of maraviroc (MVC) have produced mixed results; hence it remains unclear whether MVC has unique immunologic effects in comparison to other antiretroviral drugs. We sought to determine whether MVC has differential effects compared to tenofovir disoproxil fumarate (TDF) during initial antiretroviral therapy (ART).
Prospective study in ACTG A5303, a double-blind, placebo-controlled trial (N=262) of MVC versus TDF, each combined with boosted darunavir and emtricitabine METHODS:: A total of 31 cellular and soluble biomarkers were assayed at weeks 0 and 48. Polychromatic flow cytometry was performed on cryopreserved peripheral blood mononuclear cells (PBMC). Soluble markers were assayed in plasma using ELISA kits. Analyses were as-treated.
Analyses included 230 participants (119 in MVC arm and 111 in TDF arm). Over 48 weeks of treatment, no significant differences were detected in declines in markers of inflammation and activation with MVC versus TDF. A greater CD4 T-cell count increase (median +234 cells/mm vs. +188 cells/mm, p=0.036), a smaller CD8+ T-cell count decrease (-6 cells/mm vs. -109 cells/mm, p=0.008) and a smaller CD4:CD8 ratio increase (0.26 vs. 0.39, p=0.003) occurred with MVC. Among participants with baseline CD4:CD8 ratio<1, smaller proportion of MVC group normalized to ratio >1 at week 48 (15% and 36%, p<0.001). CONCLUSIONS
MVC resulted in less improvement in CD4:CD8 ratio driven by greater increase in CD4 count but smaller decline in CD8 count. Changes in soluble or cellular biomarkers of inflammation and immune activation were not different between MVC and TDF.