Agrarian Diet Intervention Reduces Immune Activation and T-Cell Exhaustion and Improves Metabolic Health in HIV Positive Men Who Have Sex with Men

People living with HIV (PLWH) often suffer from metabolic dysfunction. Prevotella-rich, Bacteroides-poor (PRBP) gut microbiomes are observed in men who have sex with men (MSM), a large portion of PLWH in the United States. A high-fiber/low-fat agrarian diet (AD) can be metabolically beneficial in individuals with PRBP microbiomes, and a high-fat western diet (WD) can exacerbate disease in HIV animal models. To assess the impact of diet on HIV-associated metabolic dysfunction, we conducted a 4-week intervention with HIV(+)MSM and HIV(-) controls randomized to AD or WD was conducted. AD reduced plasma IL-6 in those with elevated levels, reduced T cells exhaustion and pro-inflammatory intermediate monocytes, and altered host transcription in the colonic mucosa. The AD also reduced low-density lipoprotein (LDL) cholesterol in HIV(+)MSM, limiting risk of cardiovascular disease, with greater reductions predicted by PRBP microbiomes at baseline. Our These findings highlight the clinical utility of high-fiber/low-fat diets, particular in HIV(+)MSM with PRBP microbiomes.