The goal of this study is to characterize intersectional stigma related to gender identity, sexual behaviors, sexual orientation, race, and poverty, as a social determinant of HIV-related health among sexual and gender minorities (SGM) in the US. This proposal was developed in response to NIH’s Notice of Special Interest (NOSI) to focus on understanding the role of intersectional stigmas and how they harm health. A high prevalence of mental, physical, and sexual health problems has consistently been documented among SGM, including sexually transmitted infections (STIs), depression, and substance use. While stigma is understood to affect these outcomes, there is limited consensus on optimal intersectional stigma measurement strategies for both transgender women (TW) and cisgender men who have sex with men (cis-MSM) or on the mechanisms by which intersecting stigmas drive health disparities, including those modifiable through health and behavioral interventions. Our investigative team has an active NIMH-funded R01(R01MH110358) focused on measuring stigma related to sexual behavior and examining how this stigma drives disparities in HIV outcomes for cis-MSM using data from around the world, including from the American Men’s Internet Survey (AMIS) in the US. In addition, we developed and piloted the Transgender Women’s Internet Survey and Testing (TWIST) platform, demonstrating high burdens of anticipated, perceived, and enacted stigmas related to gender identity and their association with decreased use of HIV prevention services, greater psychological stress, and suicidal ideation among TW in the US. Here, we propose to collect data on trends in stigma and health in two cross-sectional online surveys of sexually active TW (n=3,000 in Years 2,4) and three of cis-MSM (n=10,000 in Years 1,3,5) accompanied by testing of self-collected biospecimens from 500 TWIST participants and 500 AMIS participants per survey (n=2,500 total). Consistent with NIH’s NOT-MH-20-020, we will build upon our prior foundational work to better assess intersectional stigma and its HIV and other health impacts for TW and cis-MSM in the US using a mixed-methods, transformative study designed to meet the following aims. Aim 1: Optimize metrics of intersectional stigma experienced by diverse transgender women and cisgender men who have sex with men sampled online in the US. Aim 2: Qualitatively explore perspectives of transgender women and cisgender-men who have sex with men (MSM) of how intersecting stigmas shape engagement in HIV prevention and treatment services. Aim 3a: Characterize cross-sectional relationships between intersectional stigmas and engagement in HIV prevention/treatment and gender affirmative care among national samples of TW and cis-MSM in the US. Aim 3b. Determine demographic, geographic, and temporal heterogeneities in the burden of intersectional stigmas and associations with sexual health, mental health and resilience, and engagement in HIV prevention and tr...