Reduced Gut Blastocystis Mediates Treatment-Associated HDL-C Increases in PLWH
Human immunodeficiency virus type 1 (HIV-1) remains a global health threat today, with most people living with HIV (PLWH) residing in sub-Saharan Africa (SSA). Despite the availability of antiretroviral therapy (ART), cardiometabolic complications are common. In this longitudinal multicenter study in Zimbabwe, we enrolled ART-treated (Exp), ART-untreated (Na?ve), and healthy control (HC) participants and assessed factors driving cardiometabolic markers. In two visits 24 weeks apart, fasting plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, and glucose were measured. Flow cytometry was also used to measure blood immune cell populations. Fecal samples were obtained and characterized by 16S and 18S ribosomal RNA (rRNA) sequencing to evaluate the prokaryotic and eukaryotic components of the microbiome respectively. Cardiometabolic markers were related to immune, dietary, and microbial data using linear mixed effects models and mediation analysis. HDL-C, triglycerides, and fasting blood glucose levels all increased on treatment with ART and prophylactic cotrimoxazole. Treatment-associated resolution of depleted HDL-C in the Na?ve group was associated with immune reconstitution and reductions in inflammation, alpha diversity, and prevalence of Blastocystis. Reduced inflammation mediated HDL-C improvement, while depletion in the intermediate monocytes and depletion of intestinal protist Blastocystis with treatment mediated triglyceride increases. Our findings inform a mechanistic understanding of potential effects of treatment on HIV-associated cardiometabolic health in PLWH in SSA.