Enhancing HIV-1 specific immunity as a therapeutic strategy in AIDS

HIV-1 specific immune responses unequivocally play a major role in determining the natural history of HIV-1 infection. The decreases in viral load which occur during primary infection are several orders of magnitude greater than the decreases observed when antiretroviral chemotherapy is initiated. Delineation of the range of immune effector mechanisms responsible for the brick decrease in viral replication during primary HIV-1 infection is an active research topic of high priority. To date, attempts to manipulate HIV-1 specific immune responses in vivo have resulted in relatively modest changes in HIV-1 specific humoral or cellular immune responses that have not been associated with convincing changes in viral load or with cleancut clinical benefit. Further investigation of therapeutic interventions directed at manipulating HIV-1 specific immune responses is warranted, but the same paradigms that have evolved to assess efficacy of antiretrovirals should be applied to HIV-1 specific immunotherapeutics, when making decisions regarding the expansion of pilot (Phase I/II) studies to larger scale studies with clinical endpoints.