Advanced HIV Disease: Re-Engagement in Care (ARC) - PROJECT ABSTRACT/SUMMARY HIV-associated hospitalizations remain high and Advanced HIV Disease (AHD) remain a persistent global problem despite widespread availability of antiretroviral therapy (ART). People with HIV (PWH) are more likely to be hospitalized, in the U.S. and globally, and at the time of hospitalization, gaps in the HIV care continuum (retention, adherence to ART, and viral suppression) are more widespread than seen in clinic or population-level data. After the end of a hospitalization (i.e., after discharge), PWH, particularly those with AHD, continue to face adverse events, including mortality and readmission. Unfortunately, poor outcomes during the hospital to home transition of care can occur in a blind spot in the health system as most HIV programs are anchored in outpatient/community settings and are unable to ascertain or intervene on inpatient and post-discharge deaths/disengagement in care among their clients. In this project, we will conduct a randomized clinical trial in Zambia to evaluate a novel intervention package called Advanced HIV Re-engagement in Care (ARC) to improve post-discharge outcomes of AHD. ARC entails a package of evidence-based and theory-informed elements that are delivered by supervised community health workers (CHWs) during hospitalization and in the post-discharge period. In Aim 1, we will evaluate the effect of ARC, compared to standard of care, on post-discharge mortality and other HIV and comorbidity outcomes. In Aim 2, effect mechanisms will be identified to inform future refinements to the intervention package. In Aim 3, we will investigate early implementation factors, and cost and cost effectiveness, that are expected to influence future uptake and sustainability of ARC and other interventions to improve HIV outcomes after discharge. Having U.S. researchers and U.S. universities conduct this project in Zambia provides multiple advantages to the U.S. First, because HIV is 20-50 times more common in Zambia than in the U.S., and outcomes of AHD are often suboptimal, conducting the study in Zambia allows researchers to have statistical power to evaluate effects of ARC on mortality, not just the HIV care cascade. In addition, while being evaluated in Zambia, ARC has potential application in the U.S., where CHW delivered interventions have become increasingly common as they provide cost and implementation advantages. Finally, the study aligns with NIH-supported ‘global health reciprocal innovation’ where partnerships between U.S. and low and middle-income country research teams ensure that the U.S. also benefits from international research. Study leaders are practicing HIV clinicians in the U.S., which positions then to introduce the ARC intervention package in U.S. healthcare settings should it be found effective.