The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants

PLoS One. 2010 Aug 3;5(8):e11937. doi: 10.1371/journal.pone.0011937.


Background: The pathogenesis of immunodeficiency due to human immunodeficiency virus (HIV)-1 is incompletely understood, but immune activation is believed to play a central role. Immunomodulatory agents that decrease immune activation may be useful in the treatment of HIV-1 infection.

Methodology: A randomized, double blind, placebo-controlled pilot study of leflunomide for 28 days was performed in participants with HIV-1 infection who were not receiving antiretroviral therapy. Participants randomized to leflunomide were subsequently treated with cholestyramine until leflunomide levels were below detection limit.

Findings: Treatment with leflunomide was well tolerated with mostly low-grade adverse events. Leflunomide administration reduced cycling of CD4 T cells (by ex vivo bromodeoxyuridine uptake and Ki67 expression) and decreased expression of activation markers (HLA-DR/CD38 co-expression) on CD8 T cells in peripheral blood. In addition, decreased expression of HIV-1 co-receptors was observed in both CD4 and CD8 T cells in the leflunomide group. There were no significant changes in naïve and memory T cell subsets, apoptosis of T cells or markers of microbial translocation.

Conclusions: Leflunomide was effective in reducing immune activation in the setting of chronic HIV-1 infection suggesting that targeting immune activation with immunomodulatory agents may be a feasible strategy.

Trial registration: NCT00101374.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • HIV Infections / immunology*
  • HIV-1 / physiology*
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / metabolism
  • Immunologic Factors / pharmacology*
  • Isoxazoles / adverse effects
  • Isoxazoles / immunology*
  • Isoxazoles / metabolism
  • Leflunomide
  • Lymphocyte Count
  • Male
  • Phenotype
  • RNA, Viral / blood
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Immunologic Factors
  • Isoxazoles
  • RNA, Viral
  • Leflunomide

Associated data