PROJECT SUMMARY Non–AIDS-defining cancers (NADC) are increasing rapidly and constitute the majority of cancers diagnosed in people living with HIV (PLWH). Accelerated aging in HIV and cancer lead to compromised skeletal muscle, which contribute to poor functional mobility and culminates in frailty and comorbidity. Frailty and balance impairment are common in patients with cancer and in PLWH. The insult to balance in the setting of a NADC diagnosis in conjunction with HIV infection, is very likely compounded, leading to greater frailty outcomes compared to PLWH as well as increased risk for fracture. Balance deficits impose limitations and can impede safe walking contributing to falls and falls-related complications. Our pilot data indicate that PLWH have highly impaired standing balance that is associated with inefficient weight transfer and an inability to regulate balance leading to greater fall risk. This study will use new quantitative methodologies including state-of-art technologies and engineering models to quantify functional balance, both the static and dynamic domains beyond established clinical assessment battery. These biomechanical indices may help predict frailty precursors to better understand how cancer, HIV infection and aging exacerbate each other, and could potentially inform management of mobility disorders in this patient population. Interventions to improve key aspects of balance control are likely to favorably impact safe functional mobility while performing everyday activities. A primary question at this juncture in our knowledge is whether a multi-component balance program can improve functional independence in those aging with NADC through attenuating the disabling consequences of frailty, which will inform future evidence-based multi-component interventions. This is an administrative supplement for P30 Cancer Centers Support Grants (CCSG) to stimulate research in NADCs in Aging Populations under a High Priority topic of research. Our overall objective is to comprehensively assess and compare balance and mobility in older NADC to older PLWH without NADC of similar socioeconomic background and to test the feasibility of a resistance and balance training program to improve balance, strength and physical activity. The proposed research has significant public health impact and will provide critical pilot data for a larger randomized controlled trial. Improvement of strength and postural stability is a significant and novel area of investigation in NADC.