High concentrations of Maraviroc do not alter immunological and metabolic parameters of CD4 T cells

Sci Rep. 2024 Jun 17;14(1):13980. doi: 10.1038/s41598-024-64902-y.

Abstract

Maraviroc (MVC) is an antiretroviral drug capable of binding to CCR5 receptors and block HIV entry into target cells. Moreover, MVC can activate NF-kB pathway and induce viral transcription in HIV-infected cells, being proposed as a latency reversal agent (LRA) in HIV cure strategies. However, the evaluation of immunological and metabolic parameters induced by MVC concentrations capable of inducing HIV transcription have not been explored in depth. We cultured isolated CD4 T cells in the absence or presence of MVC, and evaluated the frequency of CD4 T cell subpopulations and activation markers levels by flow cytometry, and the oxidative and glycolytic metabolic rates of CD4 T cells using a Seahorse Analyzer. Our results indicate that a high concentration of MVC did not increase the levels of activation markers, as well as glycolytic or oxidative metabolic rates in CD4 T cells. Furthermore, MVC did not induce significant changes in the frequency and activation levels of memory cell subpopulations. Our data support a safety profile of MVC as a promising LRA candidate since it does not induce alterations of the immunological and metabolic parameters that could affect the functionality of these immune cells.

Keywords: Activation markers; HIV latency; Latency reversal agents; Maraviroc; Metabolic rates.

MeSH terms

  • Adult
  • CCR5 Receptor Antagonists / pharmacology
  • CD4-Positive T-Lymphocytes* / drug effects
  • CD4-Positive T-Lymphocytes* / immunology
  • CD4-Positive T-Lymphocytes* / metabolism
  • Cells, Cultured
  • Cyclohexanes / pharmacology
  • Glycolysis / drug effects
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • HIV-1 / drug effects
  • Humans
  • Lymphocyte Activation / drug effects
  • Male
  • Maraviroc* / pharmacology
  • Triazoles / pharmacology

Substances

  • Maraviroc
  • Triazoles
  • CCR5 Receptor Antagonists
  • Cyclohexanes