Exciting new research from Université de Montréal’s affiliated hospital research centre, the CRCHUM, suggests that a common drug used to treat type 2 diabetes could hold the key to eliminating the viral reservoir in people living with HIV who are undergoing antiretroviral therapy.
Metformin, a medication known for its effectiveness in managing diabetes, has shown promising results in depleting the viral reservoir and potentially eradicating it entirely in individuals with HIV receiving antiretroviral therapy. Led by immunologist Petronela Ancuta, a team of Canadian researchers at CRCHUM conducted a study in 2021 that revealed the immunostimulatory properties of metformin, reducing chronic inflammation and enhancing immune responses in HIV patients.
The mechanism behind these positive outcomes lies in metformin’s ability to inhibit the mTOR molecule, which plays a crucial role in slowing down HIV replication within the immune cells of infected individuals. This groundbreaking finding has been detailed in the journal iScience, where Ancuta and her team explore the molecular pathways through which metformin influences HIV replication in CD4 T lymphocytes, the primary target cells for the virus.
HIV establishes reservoirs within CD4 T lymphocytes, allowing for continuous replication and contributing to persistent inflammation by triggering the immune system. However, metformin’s dual impact on the virus – enhancing infected cell numbers while preventing viral escape – signifies a significant breakthrough in HIV treatment strategies.
Unleashing the power of antibodies
Moreover, metformin has been found to upregulate the BST2 protein, facilitating the attachment of viral particles to infected cells and promoting their recognition by the immune system. Ancuta’s collaboration with Andrés Finzi has revealed that certain anti-HIV antibodies possess the ability to target and destroy virally infected cells following metformin exposure, marking a crucial step towards a potential “shock-and-kill” eradication approach for HIV.
By combining metformin with clinically approved antibodies, Ancuta envisions a novel strategy to reawaken dormant reservoir cells post antiretroviral therapy cessation, allowing for their selective targeting and elimination by the immune system. This innovative approach, if validated in clinical trials, could revolutionize current HIV treatment protocols.
In the upcoming phase of her research, Ancuta plans to initiate clinical trials to validate the efficacy of this combined treatment approach in humans, alongside her colleagues Finzi, Nicolas Chomont, and Jean-Pierre Routy. Preclinical models will serve as a preliminary testing ground before moving to human trials, ensuring the safety and effectiveness of the proposed strategy.
