Immunologic Effects of Maraviroc in HIV-Infected Patients with Severe CD4 Lymphopenia Starting Antiretroviral Therapy: A Sub-Study of the CADIRIS Trial

Abstract

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: Sub-study of a randomized, double-blind, clinical trial where patients starting ART with CD4 counts <100cells/uL received maraviroc or placebo. CD4 and CD8 maturation phenotypes, PD-1 and CCR5 expression, and activation indices were characterized at weeks 0, 4, 12, 24 and 48. CD4 and CD8 reactivity with peptides of CMV, 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 studied (Maraviroc=22; placebo=18). Sustained increases in CD8 were observed in the maraviroc arm. Significant, increases in the proportions of circulating CCR5+ CD4 and CD8; in central memory and effector memory CD8; and in the proportion of activated CD4 and CD8 were observed at week 4 in the maraviroc arm. T cell responses to CMV, MTb and SEB did not differ by treatment arms. Conclusions: The higher increases of CCR5+ and activated CD4 and CD8 in circulation without affecting CD4 recovery or antigen-specific T-cell responses strongly suggests an increased retention in circulation of CCR5+ cells due to maraviroc.

Keywords

• Immune Reconstitution Inflammatory Syndrome, HIV, maraviroc, immune activation, maturation phenotype