MACS/WIHS Combined Cohort Study (MWCCS) Administrative Supplement: Abstract. While significant recent changes in the clinical care of people with HIV (PWH) (e.g., universal ART initiation, greater use of statins as prophylaxis) have reduced cardiovascular disease (CVD) risk, concurrent developments that may increase CVD risk (e.g., shift to integrase inhibitors as first-line HIV treatment, continued aging of the HIV population) mean that the determinants of CVD in PWH are ever-changing. We have the opportunity to extend our existing MWCCS database of -omics measures in women in relation to HIV-associated CVD to men, and expand the scope with additional assessments of the microbiome, metabolome, and sex hormones. We propose to use archived specimens to measure gut microbiota and selected microbiome-related metabolites and immune marker panels, including markers of immune activation, gut barrier dysfunction and microbial translocation in relation to carotid atherosclerosis in MWCCS men, and assess both the independent and mediating roles of sex hormones in this relationship among both women and men with HIV. Our aims support HIV/AIDS research that falls under the following NIH high priority AIDS-designated topics: 1) immune dysfunction, persistent inflammation, and microbiome and genetic determinants that underpin the development of high priority HIV co-morbidities, and 2) long-term treatment or prevention strategies for HIV-relevant comorbid conditions across the lifespan.