Antidiabetic Drug Metformin Could Help Immune System Recognize HIV

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Antidiabetic medication metformin helped immune system recognized HIV, when used alongside an antiretroviral (ART) regimen, according to the results of a recent study from the Université de Montréal’s research center, CRCHUM. The full study was published online in early August 2024 in iScience. The combination also reduced chronic inflammation, a common symptom of an HIV infection.

A team of researchers led by Petronela Ancuta, Ph.D., a CRCHUM researcher and professor at Université de Montréal, studied the immune cells of 13 people on ART and metformin in 2021 and found that metformin reduced the amount of HIV in cells and increased the amount cells showing HIV on their surface by triggering the over-production of the BST2 protein, which keeps HIV virus particles glued to HIV-infected cells. The immune system therefore had an easier time identifying and fighting HIV.

“The results of our in vitro tests on cells from people living with HIV and treated with antiretroviral therapy caught us off guard at first,” Ancuta said in a news release published yesterday. “They were a bit surprising. We discovered that metformin had both a proviral and an antiviral effect. The drug helped boost the number of HIV-infected cells, while also stopping the virus from escaping the cell.”

A latent HIV reservoir is a group of old HIV-infected CD4-T lymphocytes established within the first few days of exposure. If a patient is taking ART, the reservoirs don’t typically release new virus particles. However, they could begin production again if a patient stops taking ART, even if viral count is low. These reservoirs are commonly found in the lymph nodes andthe spleen. ART alone is not effective on eliminating these reservoirs, but when used in combination with metformin, researchers found that metformin hindered the activity of the mechanistic target of rapamycin (mTOR) molecule, the molecule that helps HIV replicate.

“Although ART has saved and substantially improved the life of PWH (people with HIV), the treatment is not curative and chronic HIV-1 infection is associated with several comorbidities that represent a global health burden,” Ancuta writes in the study. “New therapeutic strategies are needed to reduce chronic inflammation, improve immune functions, and accelerated the decay of viral reservoirs.”

Ancuta said the next phase of research will be a clinical trial to validate the in vitro test results.