VIROLOGY AND IMMUNOLOGY OF ACUTE HIV1 INFECTION

University Of Texas Sw Med Ctr/Dallas, Dallas TX

Investigators

Linked publications & trials

Abstract

Description (Adapted from the Investigator's Application): In this competing renewal the experimental design has been adjusted so that maximum information on the pathogenesis of early infection from patients who are treated with potent antiretroviral therapy can be derived. The applicants have preliminary results that lead to hypothesize that the immune response during acute HIV-1 infection is being driven by excess antigen. There are several possible consequences of this strong antigen driven response. First, CTL will rapidly expand and may, under certain situations, either become clonally exhausted or they may cause the selection of CTL escape variants. The CTL response by removing that antigen drive through the introduction of antiretroviral therapy during acute infection will be addressed. Early intervention may result in reversion of CTL from an activated to a memory phenotype, and that the immune system may be able to respond appropriately if the patient is non- adherent to the therapy and viral replication resumes. Second, the applicants hypothesize that the proliferation of CD4+ T cells in response to HIV-1 antigen supplies the virus with its major source of target cells for replication during acute infection. The consequence of this scenario is that at the completion of the acute phase of injection, most of the HIV-1-responsive CD4+ T cells have been clonally deleted. If HIV-1- specific (or other antigen-specific) CD4+ T cell responses are severely depleted at the end of the acute phase of injection, and whether early intervention results in retention of these responses will be determined. Finally, the applicants believe that low levels of antigen within lymphoid tissues may serve as a nidus to maintain an active immune response to HIV- 1 and they will specifically determine if immunologic responses to HIV-1 are maintained in lymphoid tissues after they have been lost from peripheral blood.