Grant: Project Grant

Despite major advances in the past three decades, HIV-1 infection remains a major health problem, with a total of 36.9 million infected people worldwide and 2 million new infections in 2014. In Canada, new infections continue to occur among young men having sex with men as well as within the First Nations communities. Current antiretroviral therapies (ART) are highly efficient in controlling HIV replication. However, viral eradication is not achieved and ART interruptions are followed by rapid viral rebounds. The cost of life-long ART together with drug toxicity and resistance, as well as stigma, justifies the need for an HIV cure. Accordingly, the focus of this translational research proposal is to generate knowledge for the rational design of new cell-specific therapies to reduce HIV persistence and boost immune restoration. The T helper 17 (Th17) cells represent a subset of CD4+ T-cells that play a critical role in the immunity against pathogens at barrier surfaces. Studies by our group and others provided solid evidence that Th17 cells fuel HIV infection and viral reservoir persistence during ART. Briefly, i) Th17 cells are preferential infection targets and their virus-induced depletion from mucosal sites causes non-AIDS co-morbidities; ii) Th17 cells express drug efflux pumps that may render the intracellular concentrations of ART suboptimal; and iii) a fraction of Th17 cells are long-lived and harbor replication-competent HIV reservoir. This project builds on our unique expertise in the identification of molecular mechanisms governing HIV replication in Th17 cells. Specifically, our studies will explore the role of the biological clock within Th17 cells as an "Achilles heel" that could be targeted by specific drugs to prevent HIV infection and the subsequent viral reservoir reactivation. This will contribute to the ultimate goal of HIV eradication in the ART era. The feasibility of our studies is ensured by our team of experts.