PROJECT SUMMARY Significance. In Africa, AIDS is the leading cause of death among adolescent girls and young women (AGYW). In 2022, 3100 adolescent girls and young women in Africa were diagnosed with HIV every week. Despite the availability of daily oral pre-exposure prophylaxis (PrEP) for over a decade and its nearly 100% effectiveness, daily oral PrEP uptake and persistence have been inadequate, especially among AGYW in Africa. New PrEP modalities, such as long-acting injectable cabotegravir (CAB-LA), have shown promising results in clinical trials by significantly reducing the risk of HIV compared to daily oral PrEP. Beyond data from controlled trials or preference-based studies using hypothetical scenarios as they were conducted when CAB-LA was unavailable to participants, we know little about implementing CAB-LA in real-world settings in Africa. In 2024, Zambia will be among the first countries to introduce CAB-LA within their national HIV program, and the Ministry of Health (MOH) selected the University of Maryland Baltimore and Ciheb-Zambia to support its implementation. Research plan. This is a prime and time-sensitive moment to assess CAB-LA's early implementation determinants and outcomes in a real-world setting using a rigorous approach grounded in implementation science to optimize the impact of CAB-LA and prevent HIV acquisition. The proposed study, Scaling Comprehensive Access to Long-acting for Equitable and Effective Use of PrEP (SCALE-UP), aims to assess in real-time and comprehensively the first-ever implementation of CAB-LA among AGYW who are most at-risk for HIV acquisition in real-world settings in Zambia. Aims: (1) Assess implementation determinants of CAB-LA guided by the Consolidated Framework for Implementation Research (CFIR). Using qualitative methods, we will assess multi-level barriers and enablers to CAB-LA implementation encountered by adolescent girls and young women, healthcare providers, and peer mentors; (2) evaluate the early effects of CAB-LA on implementation outcomes and clinical outcomes using the RE-AIM framework. We hypothesize that adolescent girls and young women using CAB-LA will have higher PrEP persistence than daily oral PrEP users at months three and six. Team: The research team, led by Multiple Principal Investigators (MPI), has expertise in implementation science, HIV clinical care, epidemiology, qualitative and quantitative research, and has a deep knowledge of HIV response and service delivery models in Zambia for priority populations, including AGYW. In addition, the study team will work collaboratively with study advisory panels with representation from youth, healthcare providers, MOH, and PEPFAR/CDC as partners to inform, refine, and prioritize implementation strategies to optimize CAB-LA implementation. Impact: The proposed study has the potential to not only accelerate the implementation and scale-up of CAB-LA in Zambia but also provide a blueprint for other African countries that will fo...