How Metformin May Help Fight HIV

Metformin, a drug used to treat type 2 diabetes, may help deplete the viral reservoir and eliminate it in people living with HIV undergoing antiretroviral therapy, according to a study published in iScience. 

In 2021, a team of researchers from the Université de Montréal’s affiliated hospital research centre, the CRCHUM, showed that metformin, when taken for three months, improved immunity and reduced chronic inflammation associated with complications such as cardiovascular disease. These therapy benefits are so effective because metformin inhibits the activity of the mTOR (mechanistic target of rapamycin) molecule, which in turn decreases HIV replication in the cells of patients infected with the virus.

In this study, researchers assessed the molecular mechanisms of action of metformin on HIV replication in CD4 T lymphocytes, which are immune system cells that provide shelter for the virus. They noted that another benefit of metformin is that it overexpresses the BST2 protein, which acts as a glue to keep virions clinging to the surface of HIV-infected cells. In turn, the immune system identifies these cells and can target them with antibodies.

“Together with my colleague Andrés Finzi, we tested the ability of several broad-spectrum neutralizing anti-HIV antibodies to recognize viral reservoir cells after metformin exposure in vitro,” said Ancuta. “Some of them recognized the virus very well, suggesting their ability to attract and trigger the destruction of infected cells by NK cells through a process of cellular cytotoxicity.”

These recent scientific advances mean that the “shock-and-kill” eradication strategy, often used in the fight against HIV, can be foreseen in a different way, she added.

“In people living with HIV and treated with antiretroviral therapy, we could use metformin to reactivate the reservoir cells responsible for viral replication upon treatment interruption, in combination with antibodies that are already used clinically and well tolerated. These antibodies can then detect the rare infected cells and eliminate them.”