Abstract Background Doxycycline post-exposure prophylaxis (doxy-PEP) is a low-cost, effective strategy for preventing syphilis and other bacterial STI among men who have sex with men and transgender women, yet doxy-PEP remains underutilized by young Black sexual and gender minorities (YBSGM). This analysis examined sociodemographic, sexual health, and substance use factors associated with interest in doxy-PEP among an HIV status-neutral cohort of YBSGM. Methods The Networks and Neighborhoods Phase 2 (N2P2) cohort included YBSGM and our primary outcome was interest in doxy-PEP. Generalized linear models were fit to calculate the unadjusted and adjusted relative risks (RR) between interest in doxy-PEP and sociodemographic and health factors. Results A total of 538 participants were included in the analysis, with 59.9% reporting interest in doxy-PEP. Participants interested in doxy-PEP were older (RR=1.02, 95% CI: 1.00, 1.04, p=0.04), more likely to be living with HIV (RR=1.25, 95% CI: 1.08, 1.44, p0.01), and had a history of syphilis (RR=1.45, 95% CI: 1.23, 1.70, p0.01). Self-report stimulant use (RR=1.28, 95% CI: 1.15, 1.53, p0.01) and group sex (RR=1.32, 95% CI: 1.15, 1.53, p0.01) were greater among those interested in doxy-PEP. When adjusted for age, HIV status, stimulant use, history of syphilis (aRR=1.17, 95% CI: 1.05, 1.31, p=0.01) and group sex (aRR=1.14, 95% CI: 1.02, 1.28, p=0.02) remained associated with interest in doxy-PEP. Conclusion YBSGM who were interested in doxy-PEP were more likely to have had a syphilis diagnosis and participate in group sex. YBSGM with these risk factors represent an important demographic for the scale-up of doxy-PEP use.
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