Modeling HIV Rebound: Role of SIVmac251 Functional Reservoirs and Biomarkers of Reactivation

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Abstract Despite fully suppressive ART for long periods of time, HIV rebounds in the majority of individuals when ART is interrupted. Studies in this proposal will define and quantitate the functional SIV latent reservoirs in tissue to understand the contributions of both CD4+T cells and macrophages to the functional viral reservoir and viral rebound after ART interruption. The SIVmac251 ART suppressed model will be used to quantitate the functional viral reservoir in CD4+ T cells and macrophages to asses their contribution to viral rebound. Depletion of CD4 cells and reduction of the latent reservoir will be done to address whether CD4 cells are the major HIV reservoir or if latently infected macrophages significantly contribute to HIV rebound. The projects in this Program will 1) Identify the differential contribution of resting CD4+ T cells and resident macrophages to viral rebound after antiretroviral treatment interruption; 2) Identify the source of viral rebound using SIV proviral genome analysis; and 3) Use computational modeling and analyses of SIV virus rebound to understand HIV rebound.