Development and evaluation of a physical activity intervention for obese people with HIV in rural South Africa. - ABSTRACT People living with HIV (PWH) living in the global south on modern first-line antiretroviral therapy (ART) experience significant increases in body mass index (BMI). Obesity contributes to adverse health outcomes, including cardiovascular disease, diabetes, and hypertension. Interventions that promote physical activity (PA) are a particularly compelling strategy to address obesity and reduce the risk of cardiometabolic disease (CMD), but remain relatively untested, and are not part of most regional HIV treatment guidelines. The scientific goal of this K43 project is to develop and pilot-test a wearable-based PA intervention to reduce obesity and improve CMD among PWH and obesity on dolutegravir (DTG)-based ART in rural South Africa. I am a postdoctoral fellow with a PhD in Exercise Science and training in exercise physiology and HIV epidemiology leading to 15 publications (13 first-authored). My long-term career goal is to become a global expert in the development of low-cost and locally-contextualised interventions to promote PA among PWH in low-resource settings. To realise this goal, I will gain further training in 1) data science methods to measure PA using wearable devices 2) PA behavioural intervention development, and 3) the conduct and evaluation of clinical trials to promote PA and improve CMD outcomes in PWH. I will do so with mentorship from a team of world-class experts in these areas, didactic training, and conduct of the following specific aims: To establish patterns of PA and sedentary behaviour among PWH and obesity on DTG-based ART to inform the development of a PA intervention (Aim 1). I will use accelerometers to assess PA indices and sedentary behaviour among 50 obese PWH on DTG- based ART in rural South Africa. Our primary outcomes of interest will be mean steps/day, mean daily energy expenditure, mean metabolic equivalents (METs)/day and sedentary behaviour. To develop a PA intervention for obese adults living with HIV on DTG-based ART in a rural setting (Aim 2). I will use mixed methods to refine an existing PA promotion intervention for PWH by combining information gleaned from Aim 1, results from focus group discussions with Aim 1 participants and clinic nurses, data from a systematic review on PA among PWH that I am leading, and expert opinion. To assess the feasibility, acceptability and preliminary efficacy of a PA intervention to promote PA among obese PWH on DTG-based ART in a rural setting (Aim 3), I will randomize 80 obese PWH on DTG-based ART in a ratio of 1:1: to standard of care (including information on benefits of PA for health), or the contextualised, wearable PA intervention, derived in Aim 2. Primary outcomes will be feasibility and acceptability. Secondary outcomes will be change in PA patterns and CMD markers, quality of life and mental health. Completing these aims will lead to development of a contextualized PA intervention to reduce CMD risk among PWH in South Africa and provide requisite data for an R01 application I will submit in year 4 of the application to transition to research independence.