Abstract Older persons with HIV (PWH) experience high rates of non-infectious, aging-related comorbidities including frailty, diabetes (DM), and cardiovascular disease (CVD) compared to the general population. Geroscience approaches focus on therapeutically targeting fundamental aging processes to delay onset of or alleviate aging-related comorbidities. Cellular senescence is a fundamental aging process for which targeted compounds have recently been identified. This process is characterized by stable growth arrest and chronic inflammation, measurable markers of which are known as the Senescence-Associated Secretory Phenotype (SASP). Senescent cell burden and SASP-related factors have been associated with frailty, diabetes, and cardiovascular disease in persons without HIV. Compared to tissue markers of cellular senescence, soluble SASP biomarkers are easier to obtain, allowing their application more diverse clinical settings However, associations between soluble SASP biomarkers and frailty, DM, and CVD have not been well-characterized among PWH. The proposed study will examine the longitudinal associations between levels of soluble SASP biomarkers and frailty, CM, and CVD in older PWH in the AIDS Clinical Trial Group (ACTG) A5322/ HIV Infection, Aging, and Immune Function Long- term Observational Study (HAILO). This study will extend the work of our currently funded cross- sectional analysis of SASP biomarkers and frailty, DM, and CVD among HAILO participants and be the first to characterize the longitudinal associations between SASP biomarkers and these conditions of interest among PWH. The findings from this study will provide pilot data for potential biomarkers to be targeted in future interventional trials using senotherapeutic agents to prevent or alleviate frailty, DM, or CVD among older PWH.