Maraviroc Reduces the Regulatory T-Cell Frequency in Antiretroviral-Naive HIV-Infected Subjects

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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+CD25hiFoxP3+ 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.

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