PROJECT SUMMARY South Africa bears the brunt of the global HIV epidemic, with over one-fifth of the 37 million people living with HIV within its borders. While we have seen tremendous success with the scale-up of effective treatment to over 20 million people, we are at a pivotal moment in the global HIV response, and South Africa lies at the center of the effort to reach the UN Sustainable Development Goal of ending HIV as a public health threat by 2030. A critical challenge in the care continuum in South Africa is the number of people living with HIV who are not virally suppressed. In 2022, over 30% were not on ART or had a detectable viral load. Individuals with gaps in care represent a substantial proportion of those who are not virally suppressed, and those who manage to return to care continue to face challenges. In the Western Cape Province, only 29% of those with prior gaps were virally suppressed one year after restarting treatment. Drivers of engagement behavior are heterogeneous, and include individual, social, and system factors that interact dynamically over years of treatment. Differentiated Service Delivery (DSD) models of person-centered care have been shown to effectively address these barriers to care, however, to date, DSD models have been offered only to people with HIV considered ‘stable’ (i.e., retained in care and virally suppressed). Thus, those at high risk of poor outcomes are ineligible for DSD models. In response, our team intends to work with the City of Cape Town and provide the critical data needed to impact policy guidelines. We designed CARES–Club-based Adherence support for Reinforcing Engagement and Sustaining Viral Suppression for South Africans with Gaps in HIV Care–to test a scalable, evidence-based DSD model (CARES-DSD) to address individual, social, and structural barriers to long-term engagement among people with HIV who have experienced an ART interruption or unsuppressed VL (PWH-Gaps). CARES-DSD is a six-month adherence club model of care that offers flexible services with multi-month dispensing of medication de-linked from clinic processes and support from lay counselors and peers, which has been proven to sustain retention and viral suppression in the Western Cape. We propose a Hybrid Type 1 trial to evaluate the effectiveness of CARES-DSD on viral suppression among PWH-Gaps at 24 months post-enrollment, as compared to an enhanced standard-of-care (an optimized guidelines-based approach). We will recruit 300 participants from our current study (SUSTAIN, R01MH125703, MPI: Orrell/Sabin), through which we have identified persistent engagement gaps in 43% of the participants despite adherence counseling, to test this model of care. We will then assess the mechanisms of intervention impact using mixed methods, guided by the Capability, Opportunity, and Motivation model of Behavior (COM-B), and determine the implementation outcomes using Proctor’s model. Ultimately, our goal is to provide an effective and ef...