ABSTRACT In South Africa (SA), the country with the world's largest HIV epidemic, ~45.6% of transgender women (TW) may be living with HIV. Of these, estimates show that 1/3 are not in treatment. Furthermore, there is low engagement with HIV prevention behaviors, such as ever having an HIV test (20.5%) and pre-exposure prophylaxis (PrEP) use (11%). Data on syphilis outcomes, which significantly increase risk for HIV and viral load if already living with HIV, are unknown in this context; though one estimate of prevalence in SA TW is ~9%. Dual self-testing for HIV and syphilis may be a promising strategy to improve SA TW's uptake of regular HIV/syphilis testing and linkage to PrEP and/or HIV/syphilis treatment. Specifically, self-testing is overwhelmingly supported by stakeholders in SA, the infrastructure to scale-up self-testing is in place and rapidly expanding, analyses show that this strategy is life and cost-saving in SA, and PrEP and HIV/syphilis treatment are widely available. Also, self-testing may address the unique social/structural barriers affecting regular testing and subsequent linkage to services for TW, including transphobia, health system mistrust, discrimination, stigma, cost, and privacy concerns. Thus, interventions to improve dual self-testing uptake and linkage to PrEP and/or HIV/syphilis treatment following a self-test are urgently needed for SA TW. Yet, we must first address 3 critical gaps in our knowledge, since findings from studies on self-testing and linkage in other groups do not extend to TW; formative work shows TW's life context is unique, and affects self-testing/linkage differently. Gaps include TW's needs/preferences on: self-test access and uptake; logistical support needed to correctly use/interpret self-tests; and linkage to and uptake of PrEP and/or HIV/syphilis treatment following self-tests. Using the INSTI Multiplex, a dual blood-based HIV/syphilis test that delivers results in 1-minute, we use mixed-methods to inform these knowledge gaps and draft a dual self-testing and linkage to care intervention tailored to TW. Research takes place in Johannesburg, SA, brings together a gender diverse team and community advisory board (CAB), and is informed by the Mensch Model; work will occur in 3 stages. In Stage 1, we will conduct in-depth interviews (IDIs) with: N=15 TW and N=15 healthcare workers (HCW) who care for TW. TW will use INSTI Multiplex in front of a study team member to provide immediate feedback on logistical support needed to test/interpret results; they will also discuss preferences on test access, and linkage. In Stage 2, we will enroll N=80 TW to complete self-administered web- based surveys on their mobile phones. Surveys are developed from IDI themes and will identify TW's preferred intervention strategy to address each domain. We will engage a data convergence process to ensure that quantitative/qualitative findings inform one another. We will then draft the intervention using the 4 COM-B Inter...