This study aimed to assess the impact a high-fiber/low-fat agrarian diet (AD) on inflammation and metabolic outcomes in HIV positive men who have sex with men (MSM). Since the gut microbiome of MSM has been shown to have a striking resemblance to individuals in agrarian cultures, including being Prevotella-rich and Bacteroides-poor, we hypothesized that they would have particularly strong health benefits from consumption of a diet matched to their microbiome type. Sixty-six participants, including 36 HIV-positive MSM (HIV(+)MSM), 21 HIV-negative MSM, and 9 HIV negative men who have sex with women were randomized to either an AD or a high-fat western diet (WD) for four weeks. The AD reduced low-density lipoprotein cholesterol in HIV(+)MSM, with more significant reductions predicted by Prevotella-rich/Bacteroides-poor microbiomes at baseline. The AD also reduced T cell exhaustion and pro-inflammatory intermediate monocytes and altered host transcription in the colonic mucosa. Our findings suggest that tailoring diet interventions to baseline microbiome type can help promote metabolic health in HIV(+)MSM.