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

Clements, Janice; Mankowski, Joseph; Siliciano, Robert

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.

Public Health Relevance

Despite fully suppressive ART for long periods of time, HIV rebounds in the majority of individuals when ART is interrupted. The latent CD4+ T cell reservoir that persist life- long is considered the major contributor to viral rebound. A major unresolved question in HIV rebound is whether the CD4+ T cell reservoir is the only latent HIV reservoir that contributor to viral rebound. HIV also infects macrophages, however, HIV latency in these cells is not well characterize. 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.