By: Bunmi Yekini
In an unexpected twist, a drug commonly used to treat type 2 diabetes may soon play a critical role in the fight against HIV. Researchers at the Université de Montréal’s hospital research center, the CRCHUM, have discovered that metformin, when combined with antiretroviral therapy (ART), may help eliminate HIV viral reservoirs – small pockets of virus that remain hidden in the body even after treatment.
For years, HIV-positive patients have relied on ART to manage their condition. While ART has been revolutionary in reducing the virus to undetectable levels, it does not completely eliminate HIV from the body. Instead, the virus hides in CD4 T lymphocytes, immune system cells that allow HIV to persist in the body, maintaining a constant level of chronic inflammation and posing risks for future complications, like cardiovascular disease.
Led by immunologist Dr. Petronela Ancuta, the research team initially observed that metformin, already widely used for diabetes, offered unexpected benefits for HIV patients. In a 2021 study, they found that the drug improved immunity and reduced inflammation in HIV-positive individuals. Now, their latest findings, published in iScience, reveal even more promising news.
Dual Role of Metformin
Ancuta’s team, including Ph.D. holder Augustine Fert, found that metformin, by inhibiting the activity of the mTOR molecule, slowed down HIV replication in infected cells. However, the results were surprising. “Metformin had both a proviral and antiviral effect,” said Ancuta. “It helped increase the number of HIV-infected cells, while also stopping the virus from escaping the cell.”
One key factor contributing to this antiviral effect is that metformin overexpresses a protein known as BST2. This protein acts like glue, causing HIV virions—mature viral particles—to stick to the surface of infected cells. As a result, the immune system can spot the infected cells more easily and target them for destruction.
With the help of colleague Dr. Andrés Finzi, Ancuta tested broad-spectrum anti-HIV antibodies that are already in clinical use. These antibodies proved effective in recognizing the virus and triggering immune responses to kill the infected cells. The combination of metformin and these antibodies suggests a new strategy in the fight against HIV.
Towards a “Shock-and-Kill” Strategy
For years, scientists have pursued the idea of a “shock-and-kill” strategy to treat HIV. This method involves reactivating dormant HIV reservoirs, exposing them to the immune system for elimination. The CRCHUM researchers believe metformin, when paired with neutralizing antibodies, could be the key to making this approach viable.
Looking ahead, Ancuta is set to collaborate with other researchers on preclinical trials to validate these findings. Her next goal is to launch clinical trials, testing the combination of metformin and antibodies in HIV-positive patients on ART.
If successful, this innovative treatment could bring the world one step closer to a potential cure for HIV—using a medication that has been in use for over 60 years for an entirely different purpose.