Grant: Project Grant

Antiretroviral therapy blocks HIV replication and extends the life of people living with HIV (PLHIV). However, it does not eliminate the virus and should be taken for life. In addition to persistent stigma, lifelong treatment entails both health risks to PLHIV and a significant economic burden to society. As such, there is a desperate need to develop a cure for HIV infection. HIV persists in cells called "HIV reservoirs" for the lifetime of PLHIV. Reservoirs are the reason why antiretroviral therapy should be taken for life. In our quest to find a cure for HIV infection, there is a need to either completely eliminate these reservoirs, or reduce their size to allow the immune system to control them naturally (like herpes viruses). From more than 20 years of research on HIV reservoirs, it is now clear that the size of the HIV reservoir slowly decays with time on therapy, but this decay is too slow to eliminate the virus during a lifetime: HIV hides in cells that have the ability to proliferate or to persist in deep tissues such as lymph nodes and bone marrow. In this project, we propose to use novel state-of-the-art technologies developed in our laboratory to characterize and eliminate HIV reservoirs. We developed a novel assay that allows us to visualize and characterize single infected cells in blood and tissues from PLHIV. Our goal is to identify the immunological and virological features of these cells. In particular, we will focus on 1) the nature of the cells in which HIV persists to identify mechanisms that lead to their persistence and proliferation and 2) the nature of the virus to understand how it escapes recognition from the immune system. We will then functionally validate our findings by testing strategies to target these vulnerabilities in test tubes. By performing these studies, we believe we will have a better understanding of the cellular and viral factors that should be targeted to eliminate HIV reservoirs.