PROJECT SUMMARY Within the next decade, nearly 1 million people aging with HIV (PAH) using antiretroviral therapy (ART) in the United States (US) will experience multi-decade life expectancy. The goal of this project is to build a suite of modules to further the ProjEcting Age, multimoRbidity and poLypharmacy (PEARL) computer simulation model’s capacity to inform clinical decision-making and resource allocation in governmental and private healthcare systems in efforts meet the future needs of caring for PAH. The Ending the HIV Epidemic (EHE) efforts will undoubtedly re-shape the age distributions of Black/African American (AA), Hispanic, and White PAH within sex-and-HIV acquisition risk groups. Projections under various scenarios of EHE goal attainment strategies within these subgroups are needed to answer the question: “How will EHE efforts impact the number of older PAH (who need clinical care) over the next two decades?” As PAH experience a greater burden of multimorbidity than people without HIV, and disparities persist within PAH subgroups, it is essential to intervene upon shared risk factors for numerous comorbidities, such as cigarette smoking and obesity. It is pertinent to answer the questions “Can interventions on shared risk factors for numerous comorbidities reduce future multimorbidity in PAH in the US, and are such interventions cost- effective?” Smoking cessation and weight maintenance in the first 24 months after ART initiation may reduce the risk of future multimorbidity with present-day clinical and administrative decision-making. Finally, by investigating the question “What are the future healthcare costs for caring for PAH in the US over the next 2 decades?” clinical directors, health systems and state and federal policy decision-makers can prepare for costs and select cost effective interventions. The established PEARL modeling team will (a) collaborate closely with Johns Hopkins HIV Epidemic Economic Model (JHEEM) team to construct a module to simulate the impact of EHE efforts, (b) continue their beneficial partnership with the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) to construct a risk factor intervention module, and (c) construct a costing module to achieve the following among 15 PAH subgroups using ART in the US through 2040: AIM 1: To simulate the impact of EHE goals on the projected number and age distribution. AIM 2: To project the change in the multimorbidity burden with risk factor interventions. AIM 3: To estimate the cost effectiveness of interventions and project HIV- and non-HIV-related healthcare costs. The proposed aims align with the research priorities of the 2021-25 Trans-NIH Plan for HIV and HIV-Related Research and include Multidisciplinary Studies of HIV/AIDS and Aging (PAR-21-068) priority outcomes. Findings will provide key HIV epidemiologic, clinical, and health services data within 15 PAH subgroups to guide clinical management and informing healthcare resource all...