ABSTRACT In the United States, transgender (`trans') women have high rates of new HIV diagnoses, with Black, Latina, and other trans women of color representing the majority of these cases. The HIV prevention and care continua emphasize the need for reducing HIV transmission risk via regular HIV testing, consistent condom use, and linkages to HIV prevention and care, such as pre-exposure prophylaxis (PrEP) among HIV-negative individuals and antiretroviral therapy (ART) and viral suppression among people living with HIV. However, there is substantial drop-off at each step of these continua with trans women falling far behind in terms of PrEP use and viral suppression. Trans women of color experience intersectional stigma that results in unmet gender affirmation needs, which have been linked to disparities in HIV prevention and continua outcomes. Building on extensive formative work, this project seeks to test the efficacy of the Let’s Be intervention, which is an integration of evidence-based, trauma-informed HIV prevention and treatment interventions, all of which have demonstrated feasibility, acceptability, and preliminary efficacy with trans women. Let’s Be is an HIV status- neutral intervention designed to mitigate the adverse health sequelae of intersectional stigma (including HIV stigma) thereby reducing sexual risk behaviors, increasing HIV prevention uptake (PrEP use), and treatment outcomes (viral suppression). Let’s Be works at both the group- and individual-levels, comprising two peer-led components via telehealth: 1) the previously tested Sheroes status-neutral intervention, and 2) previously tested individual-level peer navigation adapted from the Healthy Divas intervention. We propose a hybrid type 1 effectiveness-implementation study focused primarily on testing the efficacy of Let’s Be, while secondarily but simultaneously gleaning important lessons during implementation. Our primary outcome is PrEP adherence/viral suppression and our secondary outcome is a composite indicator of HIV risk that acknowledges there is not a singular effective prevention strategy that is appropriate or desired by all transgender women. We will recruit and randomize 250 trans women of color from San Francisco, California and Detroit, Michigan (stratified by city and HIV status), following participants for 12 months and collecting biological (i.e., dried blood spots to measure PrEP use or viral load) and behavioral data. Our community advisory boards composed of trans women of color will provide ongoing consultation. Our hybrid type 1 effectiveness-implementation design will inform implementation considerations to scale up Let’s Be to other EHE jurisdictions, if effective. Findings will provide critical insights into the efficacy evaluation of an urgently needed trauma-informed multi-level status-neutral intervention delivered via telehealth in reducing disparities among trans women of color, one of the highest priority HIV prevention populations in the...