The American Transformative HIV Study: Protocol for a US National Cohort of Sexual and Gender Minority Individuals With HIV.

Background: Sexual and gender minority (SGM) individuals represent 2%-5% of the US population, yet continue to account for more than two-thirds of new HIV infections annually. Objective: This study seeks to identify multilevel (ie, structural, psychological, and social) and biobehavioral (ie, rectal cytokines or chemokines) determinants of amplified HIV seroconversion risk for SGM individuals, including those who use methamphetamine. Methods: The American Transformative HIV Study is an ongoing web-based cohort study of 5364 SGM individuals from all 50 US states and Puerto Rico, enrolled in 2022 and 2023, and will be followed through 2027. We oversampled persons who use methamphetamine (2846/5364, 53.1%). We used established web-based strategies to enroll individuals aged 16-49 years at high risk of HIV acquisition via sexual networking apps. To be eligible, participants had to report meeting objective criteria for HIV pre-exposure prophylaxis (PrEP) care, but not be taking PrEP. Participants complete annual web-based surveys (baseline, 12, 24, and 36 months) and are asked to provide self-collected oral fluid samples for HIV testing and 2 rectal swabs (the Aptima Multitest Swab and the Zymo DNA/RNA Shield swab) following each assessment. Oral fluid samples are analyzed immediately, while rectal swabs are banked for a future nested case-cohort analysis to assess changes in inflammatory markers following a new infection. Results: Nearly all participants (4542/5364, 84.7%) were cisgender men, 3.7% (201/5364) were transgender women, and 1.1% (61/5364) were transgender men who have sex with men. There were also 560 (10.4%) individuals who self-identified outside of the gender binary-all reported being assigned male sex at birth. In total, 56.5% (3031/5364) were persons of color, and 31.8% (1714/5365) were aged 16 to 29 years. In total, 4054 baseline HIV test kits were returned, including 371 HIV reactive samples-3.3% (69/2210) were HIV-positive among those who did not report methamphetamine use, and 15.5% (302/1944) were HIV-positive among those reporting methamphetamine use. Based on participant's HIV results as well as self-reporting when their most recent prior HIV-negative test was, we estimated that the incidence rate in this cohort in the 12-month period leading up to study enrollment was 10.06 (95% CI 8.65-11.64) per 100 person-years among those reporting methamphetamine use compared with 2.04 (95% CI 1.49-2.73) among those not reporting methamphetamine use per 100 person-years. Conclusions: A large, US national, and racially diverse web-based cohort of SGM individuals at high risk for HIV has been successfully enrolled and will be followed through 2027. Persons who use methamphetamine have been oversampled and demonstrated an exceptionally greater risk for HIV. Our study will offer insight into the development and implementation of new interventions, which aim to have a meaningful impact on HIV transmission.