Background: We aimed to describe the mechanisms of immunological recovery and the effects of blocking CCR5 in patients starting ART with advanced HIV-infection.
Methods: This was a sub-study of a 48 week double-blind, clinical trial where patients starting ART with CD4+ cell counts <100 cells/uL were randomized to receive maraviroc or a placebo. CD4+ and CD8+ cell maturation phenotypes, expression of PD-1 and CCR5, and activation indices were measured at weeks 0, 4, 12, 24, and 48. The reactivity of CD4+ and CD8+cells with peptides of CMV and MTb, and with Staphylococcal enterotoxin B (SEB) was assessed by intracellular expression of IFNγ, TNFα, and CD40 ligand at weeks 0, 4, and 12 of ART.
Results: Forty patients were included in the study (Maraviroc = 22; placebo = 18). Sustained increases in CD8+ cells and in proportions of CCR5+ CD4+ and CD8+ cells were observed in the maraviroc arm. Early increases in the proportions of activated (CD38+, HLA-DR+), PD-1+ CD4+, and CD8+ cells and more matured CD8+ cells, were observed in the maraviroc arm. T cell responses to CMV, MTb, and SEB did not differ by treatment arms.
Conclusions: During antiretroviral therapy in advanced HIV infection, maraviroc retains mature, activated CCR5+ cells in circulation without impact on CD4+ T cell recovery or T cell reactivity to antigen or superantigen.
Keywords: HIV; Immune Reconstitution Inflammatory Syndrome; immune activation; maraviroc; maturation phenotype.