Grant: Team Grant: Canadian Initiative for HIV Cure Research

Despite the success of antiretroviral therapy (ART) in decreasing mortality for HIV-infected patients, ART has not cured HIV/AIDS. The failure to eradicate HIV infection during ART stems from the virus' ability to persist in the body, in multiple cell types and tissues and, in quantities below the levels detected by standard tests. Without lifetime therapy, the virus quickly rebounds resulting in accelerated morbidity and mortality. The most commonly studied form of persistence is in CD4 cells that are "resting" and harboring virus out of view of drugs or from the immune system. However, evidence indicates that other long-lived cells, known as myeloid cells, contribute to HIV persistence. Cells that allow virus persistence are called virus reservoirs (VRs) and represent a significant barrier preventing an HIV Cure. While much is known about HIV persistence, many puzzles remain about the source of persistent HIV, the mechanisms underlying its establishment and maintenance, and the ways to eradicate VRs. The Canadian HIV Cure Enterprise (CanCURE), a collaboration of leading Canadian HIV researchers proposes an integrated and innovative research program across a number of platforms (human, animal, in vitro model) to: 1) Identify and exploit insufficiently characterized properties of myeloid cells, especially macrophages, that act as VRs and contribute to HIV persistence; 2) Conduct detailed mechanistic studies aimed at understanding how these VRs are established and maintained; 3) Identify new drug candidates that capitalize on these discoveries to reverse persistence and evaluate novel therapeutic strategies that enhance immune recognition and/or elimination of VRs; and, 4) Test whether novel immune-based therapies influence persistence in ART-treated patients in clinical trials. These studies are all aimed at finding new effective approaches to curing HIV infection in humans by eliminating persistent HIV infection from VRs in ART-treated patients.