Doxycycline post-exposure prophylaxis for STI prevention among MSM and transgender women on HIV PrEP or living with HIV: high efficacy to reduce incident STI's in a randomized trial


BACKGROUND: With a sexually transmitted infection (STI) epidemic among men who have sex with men(MSM) and transgender women(TGW), interventions to reduce STIs are needed.
METHODS: DoxyPEP is a randomized open-label trial among Seattle and San Francisco MSM/TGW living with HIV or on PrEP who had N. gonorroheae (GC), C. trachomatis (CT), or early syphilis in the past year. Randomization was 2:1 to 200 mg doxycycline hyclate within 72 hours of condomless sex or no doxycycline with STI testing at enrollment, quarterly, and when symptomatic. An independent committee adjudicated STIs. The trial had >80% power to detect a 50% reduction in STI incidence, assuming a 10% quarterly STI incidence. The intent to treat analysis compared relative risk of an STI per quarter. A single interim analysis at ~50% of follow-up time occurred May 2022; the DSMB recommended stopping the control arm based on prespecified efficacy thresholds measured independently in PLWH and PrEP cohorts.
RESULTS: Of 554 enrolled, 360 were on PrEP, 194 PWLH, 65% white, 8% Black, 10% Asian, 30% Latinx. 19 (3%) identified as TGW or nonbinary. Median sex partners in past 3 months was 9. In the past year 67% had GC, 58% CT, 20% syphilis; at enrollment, 18% had GC, 10% CT, 2% syphilis . Among 360 on PrEP, 65 STI endpoints (29.5%) occured in controls and 47 (9.6%) in doxyPEP participants (RR 0.33; 95%CI 0.23-0.47; p<0.0001). Among 194 PLWH, 30 STI endpoints (27.8%) in controls and 31 (11.7%) in doxyPEP participants (RR 0.42; 95% CI 0.25-0.75; p=0.0014). GC, CT, and syphilis were each reduced. No serious or '¥ Grade 2 AEs were attributed to doxycycline.

CONCLUSIONS: Doxycycline 200 mg taken within 72 hours after condomless sex significantly reduced STIs in MSM/TGW. Effects on antimicrobial resistance, gut microbiome, and sexual behavior are being assessed as important considerations for this STI prevention strategy.