Summary Clonal hematopoiesis (CH) is the presence of a proportion of hematopoietic cells carrying a somatic mutation that arise from a common hematopoietic stem or progenitor cell (HSPC). CH increases with aging and is an independent risk factor for hematologic malignancy as well as cardiovascular disease and all-cause mortality in the general population. People living with HIV (PWH) are at increased risk for many age-related comorbidities including cancer and CH is of emerging interest in this population as a potential prognostic biomarker. Several studies have identified a higher prevalence of clonal hematopoiesis of indeterminate potential (CHIP) in PWH compared to non-HIV matched comparators. For PWH, the intersection of genomic alterations with the persistent immune activation and inflammation characteristic of HIV infection posits a complex interplay that may accelerate aging processes and predispose individuals to age-related diseases at a higher rate than the general population. Given that PWH are at higher risk of CHIP, we propose to investigate whether CHIP could be mediating both accelerated biological aging and downstream cancer events. We hypothesize that PWH will have a higher prevalence both CHIP and methylation markers of aging than matched controls and that both will be independent risk factors for incident malignancy in PWH. Here we propose to (1) compare the prevalence of CHIP by HIV status in a health system-based cohort, (2) compare epigenetic age in a large cohort by HIV status and presence of CHIP and (3) to assess the effect of CHIP and biomarkers of aging on aging on cancer incidence and outcomes in PWH. This work will elucidate the potential interplay between CH, aging and cancer in PWH and facilitate the establishment of CH as a biomarker for potential preventive intervention within this population.