THE RATIONALE FOR IMMUNOTHERAPY IN HIV-1 INFECTION

Human immunodeficiency virus type 1 (HIV-1) infection causes progressi ve and ultimately profound immunosuppression. Initially, however, infe ction is associated with vigorous virus-specific immune responses, inc luding both neutralizing antibodies and cytotoxic T lymphocytes (CTLs) . Although the host immune response is ultimately unable to eliminate the virus, experimental data suggest that these immune responses help to inhibit virus replication during the prolonged asymptomatic phase o f illness. A number of mechanisms have been proposed to contribute to viral persistence in infected persons, among them direct immunosuppres sive effects of the virus; defects in antigen presentation; down-modul ation of human leukocyte antigens (HLA); clonal deletion of existing i mmune responses; sequence variation leading to immune escape; and decr eased T-helper cell function. The rationale supporting the use of vacc ine therapy in HIV-1 infection is based on the hypothesis that viral p ersistence is due to an inadequate immune response generated by natura l infection and that the immune system can be induced to generate more effective immunoregulatory responses by vaccination. Potential mechan isms by which this might occur include enhanced clearance of circulati ng virus, enhanced recognition of virus variants, enhanced presentatio n of viral antigens to the immune system, and increased regional T-cel l help. A number of protocols evaluating vaccine therapy in HIV-1 infe ction are presently under way, the results of which should facilitate rational decisions regarding the use of this approach in HIV-l-infecte d persons.