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

Abstract

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:

ClinicalTrials.gov NCT00101374.

• Authors: Sarah W Read, Mary DeGrezia, Emily J Ciccone, Rebecca DerSimonian, Jeanette Higgins, Joseph W Adelsberger, Judith M Starling, Catherine Rehm, Irini Sereti
• Journal: PloS one (PLoS One) Vol. 5 Issue 8 Pg. e11937 (Aug 03 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20689824 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• Immunologic Factors
• Isoxazoles
• RNA, Viral
• Leflunomide

Topics

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