Grant: TG: Biomedical Res. for HIV/AIDS/STBBI-Next-Gen.Therapeutic Interv.-Large Team

Antiretroviral therapy (ART) has dramatically increased the life expectancy of people living with HIV (PWH). However, ART is not a cure and needs to be taken for life to prevent resurgence of the virus. The failure to eradicate HIV infection during ART stems from the virus' ability to persist in the body in multiple cell types and tissues. While most of the discoveries made on HIV reservoirs during the past 40 years have used blood samples, it is now clear that the bulk of the virus persists in tissues (gut, lymph nodes, lung, brain etc.). Therefore, there is a need to better understand how these HIV-infected cells persist in these anatomical compartments with the objective of identifying novel mechanisms that contribute to their maintenance and that can be counteracted to reduce or ideally eliminate HIV reservoirs. The Canadian HIV Cure Enterprise 3.0 (CanCURE 3.0), a team of leading Canadian HIV researchers, proposes an integrated and innovative research program informed by new knowledge in the field and new findings generated under CanCURE 1.0 and 2.0 (2014-2024) to: 1) Identify the specific tissues in the human body that are most likely to harbor the viruses that cause rebound when ART is interrupted and define cellular mechanisms that can be modulated to inhibit this process; 2) Conduct detailed mechanistic studies aimed at understanding the critical role played by tissue-specific microenvironment (metabolites and immune responses) on the persistence of HIV-infected cells; 3) Identify new therapeutic strategies to tackle HIV persistence that capitalize on these discoveries and pursue the preclinical and clinical development of therapeutic interventions aimed at targeting viral reservoirs initiated under CanCURE 2.0. These studies are all aimed at finding new effective approaches to reduce viral reservoirs in PWH on ART with the ultimate goal of developing a safe, scalable and effective cure of HIV infection.