HIV: decrease inflammation

Université de Montréal

Metformin, used to treat type 2 diabetes, may reduce chronic inflammation in people on triple therapy, according to a team at CRCHUM.

While people living with HIV have improved their health with antiretroviral therapy, they are more likely to suffer from complications associated with chronic inflammation, such as cardiovascular disease. These health problems are due in part to the viral reservoirs in which HIV persists and the constant activation of the immune system.

In a pilot study recently published in EBioMedicine, researcher Petronela Ancuta, professor at the University of Montreal, and doctoral student Delphine Planas, first author of the study, assess the ability of metformin to improve immune function and reduce blood loss. size of viral reservoirs. Currently, antiretroviral therapy blocks HIV replication by acting on the entry and exit of virions. However, there remains one step that is not targeted by these therapies: the multiplication of the viral genome within the infected cell itself. Despite triple therapy, this intracellular viral multiplication causes chronic inflammation and immune activation which lead to the development of co-morbidities such as cardiovascular disease.

The idea to use metformin in people living with HIV came from Dr. Jean-Pierre Routy [Research Institute of the McGill University Health Center], our collaborator in this study. Widely used in medicine, this drug stimulates or slows down reactions of the immune system. In our study, we gave metformin to 22 non-diabetic patients on triple therapy – 13 in Montreal and 9 in Ottawa – keeping in mind that this drug interferes with the activity of the mTOR molecule [Mechanistic Target of Rapamycin]. , involved in the transcription of HIV. In vitro, inhibition of mTOR by drugs has been shown to significantly slow down HIV replication in cells of patients infected with the virus.

We were excited about the positive results of this pilot study. The drug was extremely well tolerated by the patients and we saw the beneficial biological effects of metformin in colon biopsies.

As a reminder, HIV lurks in CD4 T cells, cells of the immune system that provide shelter and form viral reservoirs in various peripheral tissues, especially in the intestine. In these reservoirs, the virus continues to multiply and causes an inflamed state.

In the study, we observed a reduction in mTOR activation in CD4 T cells in the colon, as well as a decrease in certain markers of inflammation and intestinal damage in plasma. Metformin would therefore have an intestinal effect, but also a systemic effect.