A Gender-Affirming Stigma Intervention to Improve Substance Misuse and HIV Risk among Transgender Women - The applicant seeks this K99/R00 award to achieve research independence in intervention science, with a focus on using community-based participatory research (CBPR) principles to reduce the negative psychological and behavioral sequela that result from stigma. Transgender (trans) women are at high risk for HIV and substance misuse due in part to elevations in three interrelated areas underpinned by stigma: internalized stigma, psychological distress, and healthcare avoidance. Acceptance and Commitment Therapy (ACT) improves internalized stigma, psychological distress, and treatment engagement and may thereby reduce substance misuse and HIV risk. However, the effects of a gender affirming ACT intervention on internalized stigma, psychological distress, healthcare avoidance, and subsequent substance misuse and HIV risk among trans women are unknown. Peer-led interventions are essential to decrease trans women’s sense of isolation, share skills for coping with daily sources of stigma, and encourage pride in one’s gender identity. ACT is a promising evidence-based intervention for peer delivery as ACT has been effectively delivered by non-therapists before. The applicant thus proposes to adapt ACT to create a gender-affirming wellness intervention (ACT+GA) that targets substance misuse and HIV risk among trans women (K99 phase), conduct an open pilot trial of ACT+GA (K99 phase), and then run a rigorous test of its effectiveness, acceptability, appropriateness, and feasibility (R00 phase). During the K99 phase, she will collaborate with her mentorship team and the assembled community- advisory board to develop the ACT+GA manual based on focus group (k = 4-6, n = 4-6 trans women/group) and stakeholder feedback (n = 10-15 treatment providers, organizational leaders, and peer staff), and then address any necessary refinements identified during open pilot testing (n = 10 trans women). During the R00 phase, trans women will be randomly assigned to ACT+GA (n = 62) or treatment-as-usual (n = 62). Internalized stigma, psychological distress, healthcare avoidance, substance use, and HIV risk will be assessed at baseline, post- intervention, and at three and six-month follow-up. The coordinated training plan will allow the applicant to build on her strong foundation in CBPR and scholarship of HIV disparities in sexual and gender minoritized (SGM) populations, developing new skills in three areas critical to her independence: (1) adaptation of ACT for telehealth delivery by trans women, (2) early phase behavioral intervention development and testing, (3) depth of learning and application of qualitative and longitudinal quantitative methods. During the K99 Phase, her mentorship team will draw on its sustained track record in mentoring junior scholars to full independence. This will be accomplished through regular meetings, directed readings, hands-on tutorials, and support of her activity in workshops, seminars, and conferences. Completion of the R00 phase will generate data to support a future R01 application to test the effectiveness and implementation of ACT+GA on a larger scale. The K99/R00 award will thus provide the applicant with a platform to launch her independent career in transgender health and intervention science.