Metformin Could Help Reduce Chronic Inflammation in People Living With HIV

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Although ART has helped improve the health of those with HIV, they are at a greater risk of developing complications related to chronic inflammation, such as cardiovascular disease.

Researchers at the University of Montreal Hospital Research Centre found that metformin, a drug used to treat type 2 diabetes, could help reduce chronic inflammation in people living with HIV who are being treated with antiretroviral therapy (ART).

Although ART has helped improve the health of those with HIV, they are at a greater risk of developing complications related to chronic inflammation, such as cardiovascular disease, according to the study authors.

A pilot study conducted by Petronela Ancuta, University of Montreal immunology professor, and Delphine Planas, PhD student, evaluated the ability of metformin to improve immune function and reduce viral reservoir size.

Ancuta explained in a press release how ART inhibits HIV replication by preventing the entry of virion, a complete viral particle, into new cells and its exit from infected cells. However, a step that is still not targeted by these therapies is the multiplication of the viral genome inside the infected cell, according to the study.

“Despite antiretroviral therapy, this intracellular viral multiplication causes chronic inflammation and immune activation, leading to the emergence of co-morbidities such as cardiovascular disease,” Ancuta said. “In the laboratory, we are working to identify new treatments to inhibit intracellular viral multiplication.”

She added that the team went into this study knowing that metformin interferes with the activity of the mTOR molecule involved in the intracellular multiplication of HIV genome, which led to the use of metformin to treat 22 nondiabetic people living with HIV on ART. In vitro, studies by our group and others had previously demonstrated that inhibiting mTOR with drugs inhibits HIV replication considerably in the cells of patients infected by the virus, according to Ancuta.

The study showed positive results that surprised Ancuta and Planas, as metformin was extremely well tolerated by the patients as they observed the beneficial biological effects of the drug in colon biopsies.

“HIV hides in CD4 T cells, immune system cells that shelter the virus and form viral reservoirs in various peripheral tissues such as the intestine. The virus continues to multiply in these reservoirs and leads to inflammation,” Ancuta said in a press release. “In the study, we observed a reduction in the activation of mTOR in CD4 T cells present in the colon, as well as a decrease in certain plasma markers of inflammation and intestinal damage. Metformin, then, has both intestinal and systemic effects.”

Ancuta hopes to launch a new randomized study on more than 58 participants, in which metformin will be administered over a longer period.

“We’re planning to do it over a 6- to 12-month period to validate the benefits of metformin in controlling inflammation, in part by regulating mTOR,” Ancuta said in a press release.

REFERENCE

HIV: an antidiabetic drug to reduce chronic inflammation. Udem Nouvelles. Published March 18, 2021. Accessed March 23, 2021. https://nouvelles.umontreal.ca/en/article/2021/03/18/hiv-an-antidiabetic-drug-to-reduce-chronic-inflammation/.

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