Mimiaga MJ, et al. - Researchers examined a multicity, longitudinal cohort of sexually active young transgender women (YTW) in the United States for HIV sexual risk behavior in correlation to a syndemic of 7 psychosocial problems. From Boston, MA, and Chicago, IL, 233 YTW completed behavioral surveys at baseline, 4, 8, and 12 months between 2012 and 2015. At baseline, a substantial prevalence of 7 psychosocial syndemic problems was noted that remained high at each time point: 6.4% reported polydrug use (excluding stimulants), 7.7% reported heavy alcohol use and 15.9% reported stimulant use in the past 4 months; a history of childhood sexual abuse was reported by 10%; experiencing lifetime intimate partner violence was reported 41.7%; clinically significant depressive symptoms were reported by 42.1%; and lifetime transgender-specific victimization was reported by 68.6%. The number of psychosocial syndemic problems was noted to have statistically significant positive “dose–response” relationship with condomless anal or vaginal sex over time. These findings highlight a necessity for a shift of the HIV prevention agenda toward enhanced assessment of psychosocial comorbidities and greater integration with gender-affirming and supportive mental health, violence recovery, and addiction treatment services for this population.