Effect of Leflunomide on T Cell Proliferation in HIV-Infected Patients
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will evaluate the effect of leflunomide on the life cycle of a specific immune
      cell called CD4+ T cell in HIV-infected patients. Leflunomide is approved by the Food and
      Drug Administration for treating rheumatoid arthritis. It works by blocking cell division in
      activated T cells. In HIV infection, the HIV virus causes increased activation of T cells.
      The activated cells become infected and die. Activation may also cause the death of T cells
      that are not infected with HIV. T cells are necessary for the body to fight infections and
      cancer. This study will see if leflunomide can block T-cell division and possibly reduce the
      number of cells that die, reduce the number of cells in which HIV can reproduce, and lead to
      a lower level of HIV virus in the body.

      HIV-infected patients between 18 and 65 years of age who have 1) HIV viral levels of 1,000
      copies/mL or more, 2) a CD4+ T-cell count of 350 cells/mm3 or more, and 3) a CD4+ T-cell
      count that has never been less than 200 cells/mm3 may be eligible for this study. Candidates
      are screened with a medical history, physical examination, blood and urine tests, chest
      x-ray, and electrocardiogram (EKG).

      Participants are randomly assigned to take leflunomide or placebo (a substance with no active
      ingredient) every day for 28 days. They come to the clinic three times during the first 29
      days of the study (days 1, 15, and 29) for a physical examination and review of any drug side
      effects. Patients taking placebo end their participation on day 29. Patients taking
      leflunomide stop taking the drug on day 29 and begin taking cholestyramine three times a day
      for 11 days out of the next 14 days to clear the leflunomide from their body. On day 43, they
      return to the clinic to have their leflunomide level checked to make sure that only very
      little or none of the drug remains in the body. If the level is low, patients end their
      participation on or around day 57. If the level remains high, they repeat the cholestyramine
      treatment.
    

Detailed description: 
      Increased T cell turnover is one of the main abnormalities observed in HIV infected patients
      and one of the main mechanisms leading to CD4 lymphopenia. This has led to the hypothesis
      that medications that act directly to suppress immune activation and normalize T cell
      turnover, could be used in HIV infection. The purpose of this protocol is to evaluate the
      effect of the immunomodulatory agent, leflunomide, on CD4+ T cell proliferation in HIV
      infected adults. HIV infected adults who have stable HIV viral loads and are not taking
      antiretrovirals will receive leflunomide or placebo for 28 days. CD4+ T cell proliferation
      will be measured as percent Ki67 expression, and the change in expression from baseline to
      day 28 will be compared between groups. Various studies measuring immune parameters such as
      CD4+ and CD8+ T cells counts and level of activation will be collected as well as safety
      studies and HIV viral loads. The primary study risk is adverse reaction to leflunomide. The
      study will be double-blinded randomized 2:1 (leflunomide versus placebo) and will be reviewed
      by a DSMB. Total enrollment for the study will be 18 patients.
    

Intervention name(s): Leflunomide
Intervention type(s): Drug
Intervention MeSH terms: Leflunomide
Primary purpose: Treatment
Keywords: Immunomodulatory Drug; Antiviral; Ki67+; Immune Activation; T Cell Proliferation; HIV; Activated CD4+T-cell; Proliferation