This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The generation of an effective AIDS vaccine is complicated by our limited knowledge of the correlates of immune protection during HIV and SIV infection. The goal of this project is to test the hypothesis that the cell cycle disease (CCD) is a significant contributor to the pathogenesis of AIDS.
Specific aims i nclude: (i) a detailed cross-sectional study of HIV-infected individuals to study the relationship between cell cycle abnormalities and the main markers of HIV-disease progression, including the response to HAART; (ii) a study of CCD in non-human primates with both pathogenic (rhesus macaques) and non-pathogenic (sooty mangabeys) SIV-infection; and (iii) a longitudinal analysis of CCD inpatients treated with IL-2 plus HAART or HAART alone, to test the hypothesis that IL-2 therapy recapitulates in vivo the beneficial effects of in vitro IL-2 administration on the cell cycle abnormalities. These analyses will provide relevant information on the role played by the loss of cell cycle regulation in the pathogenesis of AIDS, and could help defining the rationale for additional, immune-based interventions in a subset of HAART-treated HIV-infected patients.
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