Effect of Leflunomide on T Cell Proliferation in HIV-Infected Patients

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.