Recent research indicates that metformin, a commonly prescribed medication for type 2 diabetes, may play a significant role in improving immune system recognition of HIV reservoirs in individuals undergoing antiretroviral therapy. This discovery could pave the way for novel strategies in HIV treatment and management.
Research Findings:
A groundbreaking study led by immunologist Petronela Ancuta from Université de Montréal’s affiliated CRCHUM, and first author Augustine Fert, has uncovered that metformin may aid in the depletion and potential elimination of HIV reservoirs in patients receiving antiretroviral therapy. The study, published in iScience, builds on previous research that demonstrated metformin’s ability to enhance immunity and reduce chronic inflammation related to cardiovascular disease.
Mechanism of Action:
Metformin’s therapeutic effects are partly attributed to its inhibition of the mechanistic target of rapamycin (mTOR), a molecule that slows HIV replication within infected cells. Ancuta and Fert’s latest research delves deeper into how metformin influences HIV replication in CD4 T lymphocytes—cells that act as reservoirs for the virus. Their findings revealed that metformin exhibits both proviral and antiviral effects, unexpectedly boosting the number of HIV-infected cells while concurrently preventing the virus from escaping these cells.
Enhanced Immune Response:
An additional advantage of metformin is its role in increasing the expression of the BST2 protein, which helps to tether virions to the surface of HIV-infected cells. This enhancement aids the immune system in recognizing and targeting these cells with antibodies. Ancuta, in collaboration with Andrés Finzi, tested various broad-spectrum neutralizing anti-HIV antibodies and found that some effectively recognized and bound to the HIV-infected cells exposed to metformin. This suggests potential for these antibodies to trigger the destruction of infected cells by natural killer (NK) cells through cellular cytotoxicity.
Future Directions:
The implications of these findings suggest a potential shift in HIV eradication strategies. Ancuta envisions using metformin in conjunction with existing clinical antibodies to reactivate HIV reservoirs, allowing for targeted elimination of these cells. The next steps include initiating a clinical trial to validate these promising in vitro results. Ancuta will collaborate with Finzi, CRCHUM colleague Nicolas Chomont, and Jean-Pierre Routy from the McGill University Health Center Research Institute to advance this research. Preclinical models will be tested before progressing to clinical trials.
Conclusion:
This study highlights metformin’s potential beyond its role in diabetes management, offering new avenues for HIV treatment by enhancing immune system responses against viral reservoirs. As research progresses, metformin could become a valuable component in the fight against HIV, potentially leading to more effective eradication strategies.
Related topics:
Abbott’s Blood Sugar Monitor for Non-Diabetics Hits the Market
Insulin-Metformin Combination Enhances Healing of Diabetic Foot Ulcers, Study Reveals
UK Regulator Clears Diabetes and Obesity Drugs of Suicide Risk
