PROJECT ABSTRACT. This competing renewal to Suubi4Her study (R01MH113486-Ssewamala, PI) will examine the longitudinal impact of an evidence-based combination intervention combining economic empowerment (EE) and family strengthening (FS) on HIV risk behaviors, cognitive, and mental health outcomes among adolescent girls transitioning into young adulthood in poverty-impacted and HIV-burdened rural communities in Uganda. Specifically, the study provides a unique opportunity to examine the longer-term effects of an evidence-based combination intervention on HIV prevention (for adolescent girls who are HIV negative— including PrEP use), and care and support continuum trajectories (of adolescent girls living with HIV – including ART Adherence) during transition into young adulthood, a high-risk, yet understudied developmental stage in sub-Saharan Africa (SSA). Adolescent girls and young women (AGYW) in SSA are still disproportionately affected by high rates of HIV infection than their male counterparts. In 2022, 63% of all new HIV infections in SSA were among women and girls. This increased risk of HIV infection among AGYW is exacerbated by poverty, gender inequalities, stigma, discrimination, and disruptions to cognitive development trajectories that are widespread across SSA. Yet, less than half (42%) of countries in SSA provide HIV prevention programs designed specifically for AGYW. Alarmingly, communities with high HIV prevalence also report poor mental health, including depression and suicidal ideation. This is particularly important during the transition from adolescence to young adulthood as the brain is undergoing dramatic remodeling of dopaminergic neural networks. Adolescent brain development enhances reward-seeking and peer influence, leading to risky decisions and mental health issues without proper self-regulation, which improves in adulthood. Research indicates that poor mental health during adolescence is more pronounced among girls than boys, underscoring the pressing need for girl-targeted interventions during adolescence. The World Health Organization has recommended using multi-sectoral approaches that address both structural and family-level issues. Approaches that concurrently address poverty (e.g., via EE) and poor mental health (e.g., via FS) have a potential to concurrently reduce AGYW’s vulnerabilities to HIV, and poor mental health and cognitive functioning. Our team recently concluded a 6-year (2017-2023, with one-year no cost Extension), 3-arm cluster-randomized controlled trial, called Suubi4Her, that tested a combination intervention guided by Asset Theory and family strengthening principles among 1260 school-going adolescent girls aged 14-17 years at enrollment. In this competing renewal, we propose 3 aims: Aim 1: To examine the long-term impact of the Suubi4Her intervention on young women’s HIV risk behaviors; Aim 2: To elucidate the long-term effect of the Suubi4Her intervention on cognitive and mental health, and to ex...