Interleukin-2 Therapy in HIV Infection

Abstract

Immune cells secrete a variety of cytokines that have a profoundly significant influence on the immune system. For example, cytokines secreted by T-helper cells have a role in cellular immune response (Thl cytokines) and in antibody production (Th2 cytokines). Interleukin 2 (IL-2) is used therapeutically for immune modulation, most specifically in cancer therapy. The following report describes the mechanisms of IL-2/IL-2 receptor interaction and summarizes the rationale for using IL-2 in HIV-infected patients and briefly describes recent and ongoing clinical trials using IL-2 in HIV/AIDS disease (intravenous IL-2 therapy and subcutaneous IL-2 therapy). In one study of patients with moderate stage HIV disease, subjects taking a maximum tolerated dose of IL-2 at 12 to 15 MIU/day demonstrated durable increases in CD4 counts and a near normal return in value. Relative to the published reports, low circulating CD4 counts and high HIV viral burden appeared to be independent determinants of a poor response to IL-2. However, aggressive combination therapy with IL-2 and highly active antiretroviral therapy (HAART) (e.g., ACTG 328) holds promise for an improved immune restorative response even in patients with advanced disease.