Intentions to use PrEP among a national sample of transgender and gender-expansive youth and emerging adults: Examining gender minority stress, substance use, and gender affirmation.

Transgender and gender-expansive youth/emerging adults ages 13–24 years, experience disproportionate HIV risk, yet have among the lowest US PrEP uptake rates (< 10%). Still, factors that promote or impede PrEP outcomes for this population are poorly understood. This study examines the effects of gender minority stressors, gender affirmation, and heavy substance use on their PrEP outcomes. Data were drawn from the CDC’s 2018 START study, which included transgender and gender-expansive youth/emerging adults indicated for PrEP (N = 972). We developed a conceptual model integrating the gender minority stress and gender affirmation models. We mapped START items onto it, including distal (family rejection, medical discrimination) and proximal (internalized transphobia, perceived TGE-stigma) gender minority stressors, heavy substance use, background factors, and gender affirmation across five domains. Structural equation modeling (Mplus-8.9) was used to examine factors related to PrEP intentions. Most participants were 18–24 (68%), trans-female (46%) and White (45%). Additionally, 40% reported heavy substance use behaviors. Medical discrimination increased internalized transphobia (b = 0.097, SE = 0.034, p = 0.005) and perceived stigma (b = 0.087, SE = 0.034, p = 0.010). Family rejection also increased perceived stigma (b = 0.181, SE = 0.032, p < 0.001) and heavy substance use (b = 0.260, SE = 0.053, p < 0.001), and perceived stigma (b = 0.106, SE = 0.037, p = 0.004) increased heavy substance use. Notably, perceived stigma (b = -0.085, SE = 0.027, p = 0.002) and heavy substance use (b = -0.161, SE = 0.031, p < 0.001) decreased intentions to take PrEP, while gender affirmation increased PrEP intentions (b = 0.045, SE = 0.019, p = 0.020). Moreover, a 1-point increase in gender affirmation reduced the risk of heavy substance use by -0.179 (SE = 0.030; p < 0.001) in the presence of family rejection, and by -0.074 (SE = 0.041; p = 0.074) when perceived TGE stigma was present. This study underscores the importance of addressing heavy substance use among transgender/gender-expansive young people as a potential barrier to PrEP uptake. Future research could explore how gender affirmation acts as a protective factor against the negative impact of family rejection and perceived stigma on heavy substance behaviors among these populations.