Réservoirs du VIH et stratégies d'éradication

 

Nicolas Chomont

Université de Montréal

 

Domaine : maladies infectieuses et immunitaires

Programme Chercheurs-boursiers - Senior

Concours 2018-2019

HIV/AIDS continues to impact the health of millions of people worldwide. Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals. Despite this unquestioned success, effective therapy does not eradicate HIV rand requires life-long adherence. In addition, the possible long-term toxicity associated with antiretroviral therapy (ART), resistance, stigma and cost all contribute to the necessity of finding a cure.

In infected individuals taking ART, HIV persists as a latent virus in a small number of dormant cells that can survive for the lifetime of the host. In addition, ART may not completely block viral replication, particularly in tissues. All these cells form the "reservoirs of HIV infection" and represent the main barrier to HIV eradication. The overarching goal of my research program is to develop therapeutic strategies aimed at reducing these reservoirs, with the ultimate objective of finding a cure for HIV infection.

Multiple gaps exist in our understanding of the mechanisms involved in the maintenance of HIV reservoirs. We propose to interfere with the two main mechanisms of HIV persistence, i.e. latency and residual viral replication. We will determine if the early initiation of ART after infection can impede the establishment of the reservoir and if a longer duration of ART can reduce HIV persistence in blood and tissues (such as the gut and lymph nodes). We will also characterize the mechanisms by which HIV is able to persist in these cells and test the ability of several drugs at interfering with HIV persistence to identify combinations that will lead to the death of all reservoir cells. Our goal is to identify a combination of drugs that can eliminate all HIV reservoirs in order to design a clinical trial aimed at eradicating HIV.