Project 3: Impairment and multimorbidity among people aging with HIV and ART in South Africa – Abstract The benefits and side effects of antiretroviral therapy (ART) are fundamentally changing the age composition and multimorbidities of people living with HIV (PLHIV) in South Africa, which has the largest number of both PLHIV and people receiving ART globally. Aging PLHIV are likely to suffer from substantial cognitive impairment and dementia, physical impairment, and multimorbidities. These impairments and morbidities are likely distinct from those that people without HIV suffer from – because of the long-term effects of HIV infection; the side effects of long-term ART; and the psychosocial, behavioral, and structural characteristics of PLHIV. The research in Project 3 of the Health, Aging and Dementia in South Africa: A Longitudinal Study (HAALSI) proposal will fill a knowledge gap that is critical for health, aging, and social policy in South Africa: the population-level frequencies, types, and drivers of cognitive impairment and dementia, physical impairment, and multimorbidity among PLHIV in HIV hyperendemic communities in South and Southern Africa. To do this, we will build on the previous HAALSI HIV renewal project, and the successful partnership between the MRC/Wits Rural Public Health and Health Transitions Research Unit (Agincourt) and the Harvard Center for Population and Development Studies. First, we will quantify the national prevalence of cognitive and physical impairment across the HIV care continuum in South Africa using established cognitive batteries and physical function tests in the HAALSI National survey. We will also quantify the changes in cognitive and physical impairment across the age course and the HIV care continuum using the longitudinal the HAALSI Agincourt cohort. Second, we will identify the distinct multimorbidity profiles of people aging with HIV and ART in South Africa, using clustering analyses of biomarker, anthropometric, and cognitive and psychological data on a range of diseases and conditions, including HIV, hypertension, diabetes, obesity, hypercholesterolemia and hypertriglyceridemia, depression, and cognitive impairment and dementia. Third, we will utilize quasi-experimental methods to establish the long-term effects of HIV and ART as well as the psychosocial, behavioral, and structural characteristics of older PLHIV on cognitive impairment including dementia; physical impairment; and chronic multimorbidity in South Africa. Our research will provide the evidence that is critically needed to design policies and programs that will ensure healthy and dignified aging among the large and growing population of older adults with HIV in South Africa and the broader Southern African region.