Many adolescents and young adults (AYA, 14-24 years old) in Nigeria have a substantial HIV risk but do not receive HIV prevention services. While pre-exposure prophylaxis (PrEP), HIV self-testing, sexually transmitted infection (STI) testing, and linkage to AYA-friendly clinical services are essential, they have not been widely implemented or sustained in Nigeria. This underlines the importance of implementation science to increase the adoption and maintenance of HIV prevention services for AYA in diverse settings. Our 4 Youth by Youth (4YBY) program (NICHD UH3HD096929) leveraged participatory implementation strategies like crowdsourcing open calls and designathons and participatory learning communities to develop AYA-led PrEP uptake, HIV self-testing, and STI testing services in Nigeria. The success of this NICHD-funded Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings Implementation (PATC3H) pilot program facilitated transition to an NICHD U-supported randomized controlled trial underway in 32 local government areas. Interim data demonstrates that the 4YBY program is effective, but how to transition this research study into practice and sustain it overtime for AYA in Nigeria requires further investigation. As a multi-disciplinary research team with proven track record, we propose the following specific aims: (1) To use participatory approaches with Nigerian youth (i.e. crowdsourcing designathons and participatory learning communities) to develop new strategies for sustaining the 4YBY program; (2) To evaluate the effectiveness of a finalist sustainment strategy to sustain core elements of the 4YBY program among at-risk, HIV-negative AYA (14-24 years old) in Nigeria using a cluster randomized control trial in 32 new local areas; (3) To estimate the impact and cost-effectiveness of the overall 4YBY program. We define sustainment based on the continuation of core elements of the 4YBY program at sufficient fidelity, the continuation of intended benefits, and adequate capacity for the continuation of the program. The Youth Participatory Action Research framework and the PEN-3 cultural model will inform our study. Implementation science aspects will be guided by the Proctor’s Implementation Outcomes Framework and the Consolidated Framework for Implementation Research (CFIR). We will also estimate the cost of implementing and sustaining the 4YBY program. We are currently implementing 4YBY in 32 local areas among a general population of AYA for 24 months. Within this cohort, we will integrate the final sustainment strategy and collect data on sustainment over time. In addition, we will recruit 32 new local areas with higher risk (PrEP-eligible) AYA that will either receive the same sustainment strategy alongside 4YBY (16 areas) or a standard 4YBY program (16 areas). Findings from the proposed S-ITEST (Sustaining Innovative Tools to Expand HIV Self- testing) study will be relevan...