Understanding how Dolutegravir-based antiretroviral therapy modifies the HIV-1 latent reservoir and implications for an HIV cure

Global funding for life-sustaining therapy to treat HIV-1 has become unstable in recent years, particularly in sub-Saharan Africa, where 70% of the 37.9 million people with HIV (PWH) reside. Lifelong adherence to therapy is required as HIV integrates into the DNA of long-lived host immune cells, persisting quietly for decades with the potential to reactivate and produce HIV at any time. Prior cure strategies aimed at eliminating this reservoir have failed due to a gap in our understanding of the molecular mechanisms behind HIV persistence and decay. Previously, our group examined reservoir changes over time in Ugandan PWH and found that their reservoir significantly increased shortly after participants initiated a new therapy drug, dolutegravir (DTG). However, the assay used to measure these changes relies on cellular reactivation, unable to distinguish whether DTG increases the number of HIV-containing cells or enhances their reactivation. This project will utilize our adaptation of a molecular-based assay for the HIV subtypes in Uganda to distinguish between these possibilities. Understanding how DTG modulates reactivation potential and reservoir stability will help define molecular targets for HIV eradication strategies. This project will improve our fundamental understanding of the HIV reservoir and enhance representation of African and female PWH.

Faculty Supervisor:

Jessica Prodger

Student:

Partner:

Rakai Health Sciences Program

Discipline:

Life Sciences

Sector:

Health and Related Sciences & Technology

University:

The University of Western Ontario

Program: