Maraviroc reduces the regulatory T-cell frequency in antiretroviral-naive HIV-infected subjects

Abstract

Background: Maraviroc is the first antiretroviral (ART) drug to target a human protein, the CCR5 coreceptor; however, the mechanisms of maraviroc-associated immunomodulation in human immunodeficiency virus (HIV)-infected subjects remain to be elucidated. Regulatory T cells (Tregs) play a key role in HIV-associated immunopathology and are susceptible to maraviroc-mediated CCR5 blockade. Our aim was to evaluate the effect of maraviroc on Tregs.

Methods: We compared the effect of maraviroc-containing or -sparing combination ART (cART) on Tregs in ART-naive, HIV-infected subjects. Tregs were characterized as CD4(+)CD25(hi)FoxP3(+) on day 0, 8, and 30. Additional analysis on week 48 was performed in a subgroup of patients. The potential reduction in the frequency of Tregs among maraviroc-treated peripheral blood mononuclear cells (PBMCs) was also tested in vitro. The suppressive function of Tregs was also analyzed in maraviroc-treated Tregs.

Results: We found that maraviroc significantly reduced the Treg frequency in both the short term and 1 year after treatment initiation. In vitro experiments showed a dose-dependent reduction in the Treg frequency after treatment of PBMCs with maraviroc, although their in vitro suppressive function was not altered.

Conclusions: These findings partially explain maraviroc-associated immunomodulatory effects and open new therapeutic expectations for the development of Treg-depleting immunotherapies.

Keywords: ART naives; HIV; maraviroc; regulatory T cells (Tregs).