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The Effect of Leflunomide on Cycling and Activation of T-Cells in HIV-1-Infected Participants

  1. Author:
    Read, S. W.
    DeGrezia, M.
    Ciccone, E. J.
    DerSimonian, R.
    Higgins, J.
    Adelsberger, J. W.
    Starling, J. M.
    Rehm, C.
    Sereti, I.

  2. Author Address

    [Read, Sarah W.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. [DerSimonian, Rebecca] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Higgins, Jeanette; Adelsberger, Joseph W.] NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. [Starling, Judith M.] NIH, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA. [DeGrezia, Mary; Ciccone, Emily J.; Rehm, Catherine; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.;Read, SW, NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.;isereti@niaid.nih.gov
    1. Year: 2010
    2. Date: Aug
  2. Journal: Plos One
    1. 5
    2. 8
    3. Pages: 7
  4. Type of Article: Article
  5. Article Number: e11937
  6. ISSN: 1932-6203
  1. 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 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.

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External Sources

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  2. DOI: 10.1371/journal.pone.0011937
  3. View record in Web of Science®
  4. WOS: 000280520500005

Library Notes

  1. Fiscal Year: FY2009-2010
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