Abstract Uptake of HIV and STI testing among gay and bisexual men who have sex with men (GBMSM) in the rural southern US is low. However, HIV and STI testing is a fundamental gateway to preventive services, such as pre-exposure prophylaxis (PrEP), and treatment provision. Thus, it is critical that we identify methods to increase uptake of HIV and STI testing among this population that experiences disproportionate HIV and STI incidence. We have developed an app, Combine, that is an adaptation of HealthMindr, an app that has demonstrated efficacy in increasing uptake of HIV testing among urban GBMSM. Combine was adapted using input from GBMSM in rural areas to address issues specific to this population such as increased experiences of stigma and reduced access to culturally competent care. We propose to conduct a Type 2 Hybrid Effectiveness-Implementation randomized controlled trial to test the efficacy of Combine to increase uptake of HIV and STI testing over 24 months of follow-up and to examine the effect of different implementation strategies among GBMSM in the rural South. Combine will include components for self-administered risk assessments, developing and supporting a plan for frequent HIV and STI testing, information about PrEP, and PrEP and HIV/STI testing provider locators. Previous trials of app-based HIV prevention have included the ability to order free HIV and STI self-test kits. However, there is not a consensus among health officials around whether at-home self-tests are an optimal solution for increasing HIV and STI testing. Additionally, despite the availability of free HIV and STI self-test kits in previous studies, large proportions of men still do not complete HIV tests and even fewer complete STI tests. Thus, we will evaluate the effect of two different intervention components on HIV and STI uptake in a 2x2 factorial trial design: availability of HIV and STI self-test kits ordered through the app and a motivational interview designed to enhance the existing app content, increase self-efficacy to develop and follow through with a testing plan, and develop strategies to deal with experiences of stigma. All participants will receive the Combine app, including a locator to identify nearby HIV and STI testing centers. Men in the control arm (Arm 1) will not have the ability to order HIV and STI self-test kits and will not receive a motivational interview; men in Arm 2 will not have the ability to order HIV and STI self-test kits but will receive a motivational interview; men in Arm 3 will be able to order free HIV and STI self-test kits but will not receive a motivational interview; and men in Arm 4 will have the ability to order HIV and STI self-test kits and will receive a motivational interview. We will assess the main effects of the availability of HIV and STI self-test kits and the motivational interview on HIV and STI testing uptake, PrEP initiation, and intervention maintenance over 24 months of follow up. Our community-bas...