Advancing youth HIV prevention and care in Uganda: stakeholder-informed innovations through implementation science, protocol for a randomized controlled trial

Compared with older adults, adolescents and young adults (AYA) face greater HIV incidence and poorer outcomes across the HIV prevention and care continuum. Despite the high HIV burden, youth in sub-Saharan Africa have suboptimal uptake rates of oral preexposure prophylaxis (PrEP) and viral suppression. Although effective interventions are available, AYA exhibit low uptake and persistence due to stigma, pill burden, and accessibility challenges. The HIV Prevention and Care Interventions for Youth in Uganda (HIP-CY) study aims to explore the adoption and effectiveness of cabotegravir (CAB LA), a new long-acting injectable antiretroviral and highly efficacious PrEP choice that can mitigate barriers to the use of daily oral PrEP among AYA at heightened risk of HIV acquisition, and the SEARCH-YOUTH intervention, an efficacious multilevel strategy for improving virologic suppression in AYA aged 15–24 years living with HIV in East Africa. The HIP-CY study uses a type II hybrid (effectiveness-implementation) design to evaluate the feasibility, acceptability, fidelity, and cost-effectiveness of two evidence-based HIV prevention and care interventions (CAB LA and SEARCH-YOUTH) across five geographically distinct urban, semiurban, and rural sites in Uganda. We use the CFIR and RE-AIM frameworks to guide data collection and analysis. Our findings will provide insights into differentiated service delivery models for CAB LA and support policies that integrate CAB LA and contextualized multilevel HIV care interventions (SEARCH-YOUTH) for AYA in real-world health service delivery to reduce the incidence of HIV in Ugandan youth. Stakeholder engagement will inform scalable, policy-aligned solutions for sustainable HIV prevention and care and contribute to broader HIV control efforts across SSA. NCT06474364 Registered 13 June 20 244, https://clinicaltrials.ucsf.edu/trial/NCT06474364. Protocol version 6, dated 16 April 2025. Amendments from versions 1 to 4 incorporated REC recommendations and updated the Investigators Roster. Protocol versions 4 to 6 were updated to align with the Ministry of Health directive on integrating HIV care into chronic medical conditions.