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Patients using the doxycycline post-exposure prophylaxis (doxyPEP) treatment protocol typically take a dose of the antibiotic within 72 hours of unprotected sex. DoxyPEP has shown some encouraging real-world effectiveness with significant declines in incidence of bacterial sexually transmitted infections (STIs). However, a new study of 26,582 men who have sex with men and transgender women in California from January 1, 2023, to June 30, 2025, published in The Lancet Infectious Disease, found that doxyPEP remained effective for preventing chlamydia and syphilis but lost effectiveness against gonorrhea. Within 90 days of a doxyPEP prescription fill, effectiveness against chlamydia was 66.5% (95% confidence interval [CI] 53.6–75.9), and 60.7% against syphilis (95% CI 28.3–78.5). However, effectiveness against gonorrhea essentially decreased with –1.8% effectiveness (95% CI –18.5–12.5). Researchers observed that gonorrhea protection declined from 42.3% in early 2023 to –15.0% by June 2025. During that time in 2025, tetracycline-resistant Neisseria gonorrhoeae strains carrying a resistance gene became more common. A doxyPEP program was implemented statewide throughout California in April 2023.
Rethinking long-term strategies: The authors conclude that doxy-PEP may provide only temporary or limited protection against gonorrhea in regions with rising antimicrobial resistance. They also suggest that clinical guidelines might need to be updated.