ABSTRACT There has been great progress in the past 30 years towards controlling the HIV epidemic and the tools to end AIDS are now available. One of the most profound tools is antiretrovirals used as HIV treatment (ART) by HIV-positive individuals and pre-exposure prophylaxis (PrEP) by HIV-negative individuals. Each have tremendous benefits for HIV prevention proven in controlled research environments. For HIV serodiscordant couples, stable couples where one is HIV-positive and one is HIV-negative, these two interventions can be delivered in an integrated fashion where PrEP use is encouraged until the point when the HIV-positive partner has sustained use of ART and is no longer infectious. This strategy nearly eliminated HIV transmission within >1000 couples in our recent demonstration project but it is not clear that this intervention would be delivered as effectively in a public health setting by staff without in depth prescribing experience. Preliminary data from this study also suggest an effect of the integrated PrEP and ART strategy on ART initiation with rates close to 90% within 12 months of a recommendation to start and ART adherence with >90% of HIV-positive partners being virally suppressed within 6 months. These rates far exceed those seen in Ugandan public health clinics. A true effect of PrEP use on ART initiation and adherence, through modeled behavior or other mechanisms, would be a compelling argument to drive forward PrEP as part of Ugandan HIV prevention policy and facilitate more people to initiate and adhere to ART. Through close collaboration with the Ugandan Ministry of Health, we propose to implement scalable delivery of integrated PrEP and ART for HIV serodiscordant couples in public health clinics in Kampala, Uganda. Intervention delivery will be launched in a staggered fashion among clinics through a stepped wedge cluster randomized trial providing a rigorous research opportunity to measure the effect of the intervention on PrEP and ART initiation and adherence. To measure these outcomes using clinic records and biomarkers, we will enroll a cohort of 1248 HIV serodiscordant couples. Additionally, we will collect qualitative and quantitative data to determine if PrEP-taking is a modeled behavior that facilitates ART use and characterize the way that PrEP and ART use interact within couples and estimate the programmatic costs of the integrated PrEP and ART strategy. Results from this study will provide compelling data to inform widespread delivery of integrated PrEP and ART for HIV serodiscordant couples as a component of Ugandan national HIV prevention policy. The proposed project will launch sustainable delivery of PrEP in Uganda through public health clinics and it has the potential to demonstrate a scalable and cost-effective approach for providing powerful HIV prevention tools to HIV serodiscordant couples.