Immunological control of HIV in vivo

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Immune responses and pathologic events resulting from viral replication during acute HIV infection determine the later level of HIV in a patient, and the emergence of occasional individuals who are able to control HIV without drug therapy. Observations that the initiation of antiretroviral therapy (ART) during acute infection may permit patients to subsequently control HIV without ART also indicate that critical pathogenic events are operative during acute infection. Project 1. will evaluate the role of CD4 T cell responses to HIV antigens in the control of HIV replication in vivo, and provides an opportunity to assess what types of CD4 responses are associated with the control of HIV in the absence of antiretroviral therapy (ART). This project will Contribute to both the operational and the scientific goals of the overall program. The inclusion of a clinical protocol offering antiretroviral therapy to eligible infected individuals is essential for the recruitment of subjects with acute and early infection whose specimens will be studied in all projects of this proposal, and provides a way to follow these subjects. Our experience indicates that the availability of this protocol will serve as a major inducement for the enrollment of patients into these studies. This project will contribute to the major immunological question of the program by assessing the correlation of the development CD4 T cell responses to HIV antigens (as measured by assays examining several different components of the CD4 response) with the control of HIV replication in the absence of ART. We emphasize the identification of subjects during the earliest days of acute infection before they decide to start therapy. However because both acute and early HIV infections will be included, subjects will start therapy at different times after the onset of their infection. Sequential immunological measurements in these subjects before they start ART will provide cross sectional data on the evolution of HIV-specific immune responses in untreated infection.