Repurposing Metformin in Nondiabetic People With HIV: Influence on Weight and Gut Microbiota

Abstract

People living with HIV (PLWH) taking antiretroviral therapy (ART) may experience weight gain, dyslipidemia, increased risk of non-AIDS comorbidities and long-term alteration of the gut microbiota. Both low CD4/CD8 ratio and chronic inflammation have been associated with changes in the gut microbiota of PLWH. The anti-diabetic drug metformin has been shown to improve gut microbiota composition while decreasing weight and inflammation in diabetes and polycystic ovary syndrome. Nevertheless, it remains unknown whether metformin may benefit PLWH receiving ART, especially those with low CD4/CD8 ratio. In the Lilac pilot trial, we recruited 23 non-diabetic PLWH receiving ART for more than 2 years with a low CD4/CD8 ratio (Akkermansia muciniphila. Our study provides the first evidence that a 12-week metformin treatment decreased weight and favoured anti-inflammatory bacteria abundance in the microbiota of non-diabetic ART-treated PLWH. A larger randomized, placebo controlled clinical trials with longer metformin treatment will be needed to further investigate the role of metformin in reducing inflammation and the risk of non-AIDS comorbidities in ART-treated PLWH.