PROJECT ABSTRACT Sub-Saharan Africa (SSA), a region dominated by low-resource communities and relatively poor families, is experiencing rising HIV prevalence among adolescents and youth (AY). Household economic hardships heighten the risk for AY’s engaging in health-compromising behaviors and their poor engagement with care. This increases their risk for contracting and transmitting HIV and non-adherence to ART treatment. Economic empowerment (EE) interventions have demonstrated substantial promise in reducing HIV-related risk-taking behaviors, and improving ART treatment adherence and mental health outcomes. Based on 10+ years of research utilizing savings-led EE interventions focused on HIV prevention, care and support for AY affected by HIV [AYaAIDS] (including AY living with HIV [AYLHIV]; and AY orphaned by AIDS [AYoAIDS] in SSA, our group has demonstrated the effectiveness of a multi-component EE intervention, Bridges, in four NIH-funded randomized control trials (RCT) in Uganda (R01 HD070727, R01HD074949, R34MH081763, R01MH113486), and one foundation-funded study in Kenya. Bridges involves: 1) financial literacy training (FLT) and mentorship; 2) family income-generating activities (IGA); and 3) incentivized savings via a matched Youth Development Account (YDA). Bridges has demonstrated robust effects on HIV-related risk-taking behaviors, ART adherence, mental health, psychosocial outcomes, educational achievement, family economics, and family cohesion. Yet, scaling EE interventions has been a challenge, signaling the need to identify and test scale-up strategies and examine determinants of implementation and sustainment. In Bridges2Scale, we will compare two multifaceted strategies (standard vs enhanced) for scaling Bridges in a two-arm Hybrid III effectiveness-implementation cluster RCT. The standard implementation strategy has been applied in our prior RCTs and involves educational meetings that prepare staff to deliver Bridges with minimal disruption to site workflow. This will be compared to an enhanced strategy that will be developed using Implementation Mapping. We will use the public school system to recruit 1440 AYaAIDS (ages 13-17 years) from 48 schools in the Greater Masaka region of Uganda, a region with 11.7% HIV prevalence. Schools will be the unit of randomization (n=24 schools per arm; n=720 students per arm). Four specific aims guide our study: Aim 1. Compare the implementation effectiveness of the standard implementation strategy vs. an enhanced implementation strategy; Aim 2. Determine the clinical effectiveness of Bridges implemented via a standard vs. enhanced implementation strategy; Aim 3. Explore implementation processes, mechanisms, and determinants; and Aim 4. Compare the cost and cost-effectiveness of the two implementation strategies. The study will address a critical challenge: how to best support the implementation, scale-up, and sustainment of EE interventions, which have been proven to be highly efficacious in...