Project Summary / Abstract The widespread use of combination antiretroviral therapy (cART) has significantly increased the lifespan of people living with HIV (PLWH). As HIV has become a chronic disease, there is a growing concern of the disproportionate risk of a variety of comorbidities. In our parent award, we are focused on two comorbidities that occur at a higher prevalence in cART treated PLWH - bone loss and fat gain. Our proposal focuses on the contribution of antiretrovirals to the development of these two conditions and utilizes a novel preclinical mouse model of HIV infection and cART treatment and human subjects data from a large-scale NIH-funded cohort study of PLWH. The current administrative supplement seeks to leverage these ongoing studies to extend our efforts into pain research and to generate supporting evidence towards a future scientific direction in pain research. Specifically, we seek to investigate musculoskeletal pain, which is a common concern of PLWH in patient reported outcome studies. We will leverage our ongoing animal work to investigate the biological mechanisms (Aim 1) and our ongoing collaboration with the MWCCS to obtain define the joint- specific patterns of musculoskeletal pain in women living with HIV (Aim 2). If successful, the supplemental aims will generate exciting new data on the prevalence and potential risk factors for musculoskeletal pain development in PLWH and provide the PI with experience and preliminary data to further research pain mechanisms in this vulnerable population. Importantly, the supplemental aims align with several areas of scientific interest within NIAMS, including focusing on immune mechanisms of pain, making large data sets relevant to pain research, and leveraging existing datasets for secondary analysis for pain research.