PROJECT SUMMARY Adolescents and young adults (AYA) are disproportionately affected by HIV in the US. Despite adolescents accounting for over 20% of new infections, this age group is the least likely to be tested for HIV, linked to care, and achieve viral suppression as compared to their adult counterparts. Further, AYA also have low rates of HIV Pre-Exposure Prophylaxis (PrEP) awareness and uptake. Therefore, there is an urgent need to expand HIV screening and prevention strategies to nontraditional healthcare settings such as emergency departments (ED) to reach AYA who would otherwise not receive preventive healthcare. The goal of this application is to leverage our recent insights obtained from a multi-center, ED-based, adolescent gonorrhea and chlamydia screening study to determine the most clinically and cost-effective HIV screening approach for AYA that will also use digital health and rapid start PrEP or antiretroviral therapy (ART) for at risk youth. This will be accomplished through the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) by leveraging its infrastructure which includes geographically diverse site consortiums including adolescent clinics and their associated pediatric EDs. This research will contribute to the evidence base for creating clinically effective, cost-effective, and sustainable HIV screening programs that can be successfully implemented into the clinical workflow of the ED. It will also improve identification and linkage to PrEP/ART care for at risk adolescents using mHealth strategies by first identifying AYA who are PrEP/ART candidates based on their responses to a computerized sexual health screen (cSHS) and subsequently providing clinical decision support (CDS) to providers via the electronic health record and educational information by text message directly to PrEP/ART candidates based on their HIV results. This intervention will rely on an innovative approach that electronically integrates patient-reported data to guide CDS. This work is significant because it has the potential to fill gaps in the literature needed to provide evidence for the best method of HIV screening in a pediatric ED setting. First, we will conduct a pragmatic comparative effectiveness trial of targeted HIV screening (screening only those disclosing high risk sexual behavior) versus universally offered HIV screening (both opt-in and opt-out methods offered to all, regardless of risk) through electronic integration of patient reported data for provision of CDS and identification of PrEP candidacy. Based on HIV test results, we will then harness digital health for status neutral rapid or same-day mHealth PrEP/ART start (SMART) and linkage to care. This research is novel in that it shifts the usual clinical practice paradigm of HIV screening and prevention in the pediatric ED from a scattered approach to a consistent and sustainable approach that is critical to addressing the HIV epidemic among AYA.