Project Summary / Abstract This study will investigate the epidemiology, clinical implications, and immunologic and infectious determinants of aging-related diseases and outcomes in older people with HIV (PWH) in Brazil. In part a result of the long- term effects of HIV infection and ongoing inflammation, older PWH experience high rates of non-communicable diseases (NCDs) and early onset of geriatric syndromes including frailty, disability, and cognitive decline. However, HIV is not alone as a chronic infection that can cause inflammation and other immunological changes associated with these outcomes. Our knowledge of how other chronic infections endemic to low-and middle-income countries affect the pathogenesis and epidemiology of geriatric syndromes in is lacking. A middle-income country with a large population of older PWH, Brazil has a history of comprehensive HIV care as well as endemic chronic infections. This diverse, longitudinal study will recruit PWH on antiretroviral therapy ≥50 years of age in three Brazilian cities (n=360 ages 50-64years and n=340 ages ≥65 years) to evaluate the ways coinfections such as TB, HTLV-1, Chagas disease, toxoplasmosis, and others affect the epidemiology and immunologic pathways of aging-related morbidity. We will examine the association of syndemics of coinfections and social determinants of health with validated NCDs. We will prospectively evaluate how individual and cumulative burden of coinfections predict incident geriatric syndromes. We will evaluate a novel screening tool to assess vulnerability of older PWH for adverse clinical outcomes including death, hospitalization, and new disability. This study will also investigate how coinfections affect biologic pathways of inflammation which contribute to development of NDCs and geriatric syndromes Building upon established and productive collaborations in HIV observational research in Latin America, this study is uniquely positioned to provide urgently needed, high-quality data to understand aging with HIV in a global context. It will offer novel insights into a diversity of infectious contributions to cellular mechanisms of aging experienced by PWH around the globe.

Project Narrative/Public Health Relevance With greater access to effective treatment, adults with HIV around the world are living to older ages. However, we have little knowledge about aging-related conditions, such as frailty and disability, or their causes in older adults with HIV in low- and middle-income countries where the HIV epidemic is greatest. Understanding how local socioeconomic factors, chronic coinfections, and comorbidities contribute to aging-related diseases and outcomes in older adults with HIV is critically important as life expectancies improve worldwide.