Maraviroc intensification of cART in patients with suboptimal immunological recovery: A 48-week, placebo-controlled randomized trial

Abstract

Objective The immunomodulatory effects of the CCR5-antagonist maraviroc might be beneficial in patients with a suboptimal immunological response, but results of different cART (combination antiretroviral therapy) intensification studies are conflicting. Therefore, we performed a 48-week placebo-controlled trial to determine the effect of maraviroc intensification on CD4⁺ T-cell counts and immune activation in these patients. Design Double-blind, placebo-controlled, randomized trial. Methods Major inclusion criteria were 1. CD4⁺ T-cell count <350 cells/μL while at least two years on cART or CD4⁺ T-cell count <200 cells/μL while at least one year on cART, and 2. viral suppression for at least the previous 6 months. HIV-infected patients were randomized to add maraviroc (41 patients) or placebo (44 patients) to their cART regimen for 48 weeks. Changes in CD4⁺ T-cell counts (primary endpoint) and other immunological parameters were modeled using linear mixed effects models. Results No significant differences for the modelled increase in CD4⁺ T-cell count (placebo 15.3 CD4⁺ T cells/μL (95% confidence interval (CI) [1.0, 29.5] versus maraviroc arm 22.9 CD4⁺ T cells/μL (95% CI [7.4, 38.5] p = 0.51) or alterations in the expression of markers for T-cell activation, proliferation and microbial translocation were found between the arms. However, maraviroc intensification did increase the percentage of CCR5 expressing CD4⁺ and CD8⁺ T-cells, and the plasma levels of the CCR5 ligand MIP-1β. In contrast, the percentage of exvivo apoptotic CD8⁺ and CD4⁺ T-cells decreased in the maraviroc arm. Conclusions Maraviroc intensification of cART did not increase CD4⁺ T-cell restoration or decrease immune activation as compared to placebo. However, ex-vivo T-cell apoptosis was decreased in the maraviroc arm.