Understanding the HIV-APOBEC3G interaction to prevent HIV persistence

Starting ART within a several month “restorative window” after HIV acquisition increases CD4+ T cell count back to normal levels; initiating ART later does not. Subjects who start viremia-suppressing ART this early also have smaller latent provirus reservoirs. In a minority of subjects starting ART before the end of the “restorative window”, the body achieves “post-ART control” that prevents viremia from rebounding for a prolonged period when ART is stopped only a few years later. It is unknown how this occurs, but such a “sustained remission” has never been seen in subjects starting ART after the “restorative window” closes. It is hypothesized that starting ART early preserves host defenses that are lost if HIV replicates longer. This project will study specimens from recently infected, as well as chronically infected, subjects to define if loss of the APOBEC3G defense accounts for expansion of persistent HIV reservoirs in blood resting memory CD4+ T lymphocytes, and the increased endogenous retroelement expression previously observed in HIV-infected persons that may contribute to sustained immune activation. If so, results from this project will support applications for further research to preserve or increase APOBEC3G and similar defenses that will diminish HIV reservoirs and abnormal immune activation.