Our research group consists of laboratory scientists who study immunological and virological aspects of human immunodeficiency virus (HIV) infection, and clinical scientists who conduct trials of pharmacological and immunological interventions in HIV-infected patients. We are investigating HIV-specific cellular immune responses in HIV-infected long term nonprogressors, and immune responses provoked by HIV-infection and by HIV vaccines administered to subjects already infected. Some vaccines can induce novel immune responses not stimulated by the infection itself. In addition we are evaluating strategies for eliciting HIV-specific immune responses against conserved conformational epitopes of the HIV envelope protein that might be useful in the design of a preventive vaccine. The mechanisms by which HIV infection leads to the destruction of enormous numbers of CD4 lymphocytes are unclear. We demonstrated that HIV-infected cells can trigger the rapid death by apoptosis of a much larger number of uninfected resting CD4+ cells, without infecting them and without the formation of synytia. The initiation of apoptosis requires the interaction of gp120 on the infected cell with CD4 on the uninfected cell. Measurements used in these investigations include: lymphocyte proliferation, cytotoxic T cells against HIV-expressing targets, neutralization of HIV by antibodies, quantitation of HIV, gp120-CD4 binding assays, ELISAs, apoptosis by several techniques, analytical, and sorting flow cytometry. We currently are conducting a large NIH-funded study of acute HIV infection