Grant: TG: Biomedical Res. for HIV/AIDS and STBBI-Next-Gen. Therapeutic Interventions

Current treatments for human immunodeficiency virus (HIV) control viral replication but do not cure the infection. This is because the virus "hides" in a few immune cells, establishing a reservoir, from which it can "re-emerge" when treatment is interrupted. We aim to better understand the cells that make-up the reservoir and develop strategies to eliminate them. Most people living with HIV (PLWH) on treatment have all the immune elements required to eliminate virus-infected cells but fail to do so likely because their immune system cannot detect the envelope glycoprotein (Env) of the virus. Our new drug exposes Env, allowing the immune cells to detect and eliminate infected cells. In this proposal, we will enhance this strategy in several ways: 1- we developed "Env-Flow", a new method to detect cells that constitute the reservoir, enabling us to identify and better characterize them, 2- we will test new methods to "wake" the virus up in these cells so it produces Env, 3- we will render these cells more susceptible to elimination by "forcing" them to express proteins that aid immune recognition, 4- we will improve the killing capacity of specialized immune cells. Our approach will be assessed using cells from PLWH (ex-vivo) and in an animal model (in vivo). This strategy brings us closer to eradicating HIV.