PROJECT SUMMARY South Africa continues to shoulder the highest burden of people living with HIV (PLHIV) in the world. In an effort to minimize the national burden of the HIV epidemic, South Africa has been at the forefront of adopting biomedical prevention. Still there is work to be done, as key populations (vulnerable patients, young men and women) are still not accessing lifesaving preventative and therapeutic HIV services. The ED provides care to high volumes of adults who may not otherwise interact with the health system, and thus is an important testing and linkage to care venue. A Universal Test-and-Connect (UTC) strategy promotes access to both preventative (pre- and post-exposure prophylaxis) and therapeutic (ART initiation) HIV services from the ED. It can expand care to otherwise missed populations and aligns directly with a differentiated service delivery model that is integrated within existing, sustainable service delivery venues. This status neutral approach has the ability to normalize HIV services in a venue that is untouched but shows great promise. The goal of this R34 proposal is to integrate UTC in two high volume EDs (one a high-volume tertiary care trauma center and another a high-volume district level facility) in Cape Town, South Africa. We first aim to integrate HIV assessment over a period of one year into routine care to define the prevalence and key characteristics of ED patients eligible for UTC interventions (Aim 1). We then seek to pilot (N=100) the delivery of oral and long-acting pre-exposure prophylaxis (PrEP) to ED patients (Aim 2). This has never been trialed before in the ED context in South Africa, and we seek to determine the preliminary uptake of PrEP (oral and long acting) in ED patients, as well as PrEP continuation at six weeks. Lastly, we propose to determine the operational feasibility of UTC using value stream mapping to map patients journeys in the ED and determine healthcare worker acceptability using the normalization process theory framework to guide physician and nursing surveys (N=160) and in-depth interviews (N=40). This new collaboration between Johns Hopkins University and the Desmond Tutu HIV Foundation brings together our complementary expertise in ED-based HIV service delivery and action research to reach missed populations. Together we seek to deliver the ED as an untapped partner in the fight against HIV, so that all populations can access life changing preventative and therapeutic HIV services.