IMMUNOMODULATORY APPROACHES TO THE THERAPY OF AIDS

Immune-based therapies are being explored on the presumption that host response to HIV is central to the pathogenesis and progression of HIV infection. Specific immune responses in most individuals serve to lim it the acute stage of infection and induce a more chronic form of vira l infection. Thus, immune response to HIV appears to be critical to vi rus control. On the other hand, HIV infection induces widespread activ ation of immune cells, which in turn contributes to further HIV produc tion. Also, immune dysfunction contributes to the development of a num ber of clinical disorders of AIDS, including opportunistic infections, wasting syndrome, AIDS dementia complex, Kaposi's sarcoma and lymphop roliferative disorders. Immune-based therapies in AIDS are directed at answering 2 major questions. Can specific HIV immunity be manipulated to better contain and reduce established HIV infection, and how can t he pathogenic processes induced by HIV infection be reversed so as to maintain or restore normal function and health? The interventions expl ored thus far have been directed towards enhancement of specific immun e mechanisms early in infection, restoration of defective functions an d reduction of excessive activation secondary to cytokine derangement in HN infection. Effective therapies developed to date include interfe ron-alpha for Kaposi's sarcoma and intermittent interleukin-2 (5-day c ourses every 8 weeks) to increase CD4+ counts. With greater understand ing of the immunopathogenesis of HN infection, better focused and pote ntially more effective therapies can be expected. Immune-based therapi es are created from an understanding of the immunepathogenesis of HIV infection. As knowledge of pathogenesis increases, more effective mean s of controlling HIV replication and immune damage are det eloped. Imm une therapies are also designed to maintain normal host immune functio ns and thus reduce the likelihood of opportunistic diseases. However, the immunopathogenic mechanisms underlying HIV infection and AIDS are complex and involve multifaceted interactions of the virus with the im mune system.