Dr. Jean-Pierre Routy
McGill University Heath CentreView Bio
Antiretroviral drugs have been very successful in improving the health of people living with HIV but these individuals still experience persistent health complications, even those who respond well to treatment. These health complications are in part due to chronic inflammation and HIV that remains hidden in immune cells, known as a viral reservoir. This study is evaluating the ability of metformin, a drug used to treat type 2 diabetes, to improve immune function and reduce the size of the HIV viral reservoir.
The increase in long-term health complications seen in those receiving treatment for HIV are a result of a number of factors. Some of these health issues are due to viral reservoirs, persistent activation of the immune system, and bacterial changes in the gut.
Metformin, the most popular medication for treating type 2 diabetes, is well tolerated and has no major side effects. It has been linked to anti-aging and weight reduction in people without diabetes. Metformin may improve the recovery of the immune system in people living with HIV who are on antiretroviral treatment. In people not living with HIV, it has also been shown to positively impact the microbes in the gut and reduce inflammation, both of which could help to improve the long-term health of those living with HIV.
This 24-week study included 23 participants. Metformin was taken in pill form twice a day for the first 12 weeks of the study. Study participants continued to take their antiretroviral treatment during the entire 24-week study period. Testing was conducted at the beginning, 12 weeks, and 24 weeks of the study. This allows researchers to assess the impact of taking metformin on immune function and if the effects of the medication continue after treatment is stopped.
The study treatment regimen decreased weight of participants, independent of changes to diet or physical activity levels. Metformin did not affect CD4 or CD8 T-cell count, or the CD4/CD8 ratio. Blood and stool sample analysis indicated that a 12-week metformin treatment promoted beneficial microbes in the microbiota, with a slight reduction in some inflammation markers. As a pilot trial, the results of CTNPT 027 indicate the potential benefits of metformin; larger clinical trials with a longer treatment are required to further investigate the role of metformin in reducing inflammation and the risk of comorbidities in people living with HIV receiving ART.
Metformin has also been hypothesized to inhibit HIV replication through its effect on cellular signaling pathways, but this has not been definitively demonstrated in humans. Using blood and colon biopsies from CTNPT 027 participants, the study team investigated the effect of metformin on the immune system and viral characteristics (HIV reservoirs). The analysis showed that a 12-week regimen of metformin did decrease HIV transcription in the colon of some CTNPT 027 participants, among other positive immunological and inflammatory changes.
If you would like more information on this clinical study, please contact the Principal Investigator.
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