The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD41 T-cell recovery: A randomized trial

The CCR5 inhibitor maraviroc has been hypothesized to decrease T-cell activation in HIV-infected individuals, but its independent immunologic effects have not been established in a placebo-controlled trial. We randomized 45 HIV-infected subjects with CD4 counts <350 cells per mm³ and plasma HIV RNA levels <48 copies per mL on antiretroviral therapy (ART) to add maraviroc vs placebo to their regimen for 24 weeks followed by 12 weeks on ART alone. Compared with placebo-treated subjects, maraviroc-treated subjects unexpectedly experienced a greater median increase in % CD381HLA-DR1 peripheral blood CD81 T cells at week 24 (12.2% vs 20.7%, P =.014), and less of a decline in activated CD41 T cells (P <.001). The % CD381HLA-DR1 CD41 and CD81 T cells increased nearly twofold in rectal tissue (both P <.001), and plasma CC chemokine receptor type 5 (CCR5) ligand (macrophage-inflammatory protein 1β) levels increased 2.4-fold during maraviroc intensification (P <.001). During maraviroc intensification, plasma lipopolysaccharide declined, whereas sCD14 levels and neutrophils tended to increase in blood and rectal tissue. Although the mechanisms explaining these findings remain unclear, CCR5 ligand-mediated activation of T cells, macrophages, and neutrophils Via alternative chemokine receptors should be explored. These results may have relevance for trials of maraviroc for HIV preexposure prophylaxis and graft-versus-host disease. This trial was registered at www.clinicaltrials.gov as #NCT00735072.