The effect of leflunomide on cycling and activation of T-cells in HIV-1-infected participants.
Author(s): Read SW, DeGrezia M, Ciccone EJ, DerSimonian R, Higgins J, Adelsberger JW, Starling JM, Rehm C, Sereti I
Affiliation(s): Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Publication date & source: 2010-08-03, PLoS One., 5(8):e11937.
Publication type: Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
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 naive 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: ClinicalTrials.gov NCT00101374.