Metformin, a medication traditionally used to manage type 2 diabetes, shows promise in reducing and potentially eradicating the viral reservoir in individuals living with HIV who are on antiretroviral therapy, according to a recent study by Canadian researchers.
Scientists at the CRCHUM, the research center connected to Université de Montréal, believe that this finding could significantly lower and possibly eliminate the viral loads in patients receiving antiretroviral treatment.
In a new study, Canadian researchers highlight that metformin may aid in diminishing the viral reservoir and potentially eliminate it entirely in HIV-positive individuals undergoing antiretroviral therapy.
A research team led by immunologist Petronela Ancuta from CRCHUM demonstrated in 2021 that after taking metformin for three months, patients experienced improved immunity and a reduction in chronic inflammation that often leads to complications like cardiovascular disease.
The effectiveness of these benefits arises from metformin’s ability to inhibit the mTOR (mechanistic target of rapamycin) molecule, which subsequently slows HIV replication within the infected cells.
In the journal iScience, Ancuta and her graduate student Augustine Fert, the lead author of the study, explored the molecular effects of metformin on HIV replication in CD4 T lymphocytes, which are immune cells that harbor the virus.
In these viral reservoirs, HIV continues to replicate, leading to persistent inflammation by constantly stimulating the immune response.
“The results from our laboratory tests on cells from HIV-positive individuals receiving antiretroviral treatment were initially unexpected,” Ancuta shared. “They were quite surprising. We found that metformin exhibited both a proviral effect, increasing the number of HIV-infected cells, and an antiviral effect, preventing the virus from escaping those cells.”
Antibodies to the rescue
Another advantage of metformin is that it boosts the expression of the BST2 protein, which helps attach virions to the surface of HIV-infected cells. This enables the immune system to recognize and target them with antibodies.
“Along with my colleague Andrés Finzi, we assessed how various broad-spectrum neutralizing anti-HIV antibodies could identify viral reservoir cells after exposure to metformin in the lab,” Ancuta explained. “Some antibodies recognized the virus effectively, indicating their potential to entice and trigger the destruction of infected cells by NK cells through cellular cytotoxicity.”
These groundbreaking findings suggest a new perspective on the “shock-and-kill” strategy often employed in HIV treatment, she remarked.
“In HIV-positive individuals on antiretroviral therapy, metformin could be used to reactivate reservoir cells responsible for viral replication when treatment is paused, in conjunction with clinically used antibodies that are well-tolerated. These antibodies would then identify and eliminate the rare infected cells.”
As the next step in her research, Ancuta intends to initiate a clinical trial to confirm her laboratory findings, collaborating with Finzi and fellow CRCHUM researcher Nicolas Chomont, as well as Jean-Pierre Routy from the McGill University Health Centre Research Institute.
Prior to advancing with this approach, she will conduct preclinical tests.
