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The following is a summary of “Doxycycline to prevent bacterial sexually transmitted infections in the USA: final results from the DoxyPEP multicentre, open-label, randomised controlled trial and open-label extension,” published in the March 2025 issue of Lancet Infectious Diseases by Luetkemeyer et al. 

Doxycycline post-exposure prophylaxis (doxy-PEP) emerged as a promising intervention for reducing bacterial sexually transmitted infections (STIs).  

Researchers conducted a retrospective study to analyze the impact of doxy-PEP on STI incidence and antimicrobial resistance in men who have sex with men and transgender women over 12 months, with an open-label extension (OLE).  

They performed DoxyPEP in Seattle (WA, USA) and San Francisco (CA, USA) among men who have sex with men and transgender women with at least 1 bacterial STI history. Participants were randomly assigned 2:1 to doxy-PEP (200 mg delayed-release tablets taken 24–72 hours after condomless sex) or standard care. The primary outcome was quarterly detection of Neisseria gonorrhoeae, Chlamydia trachomatis, or early syphilis, assessed in the modified intention-to-treat with at least 1 follow-up quarter (~3 months). After early termination, all remaining participants were offered doxy-PEP in an OLE. Quarterly bacterial STI incidence was analyzed for both periods, and safety was assessed using follow-up data. 

The results showed that 637 participants were enrolled from Aug 19, 2020, to May 13, 2022, with 592 completing at least 1 follow-up in the randomised phase (411 in the doxy-PEP group and 181 in the standard-care group) and 282 in the OLE (207 in the doxy-PEP and 82 in the standard-care). In the randomised phase, STIs occurred in 129 (12.0%) of 1077 quarters in the doxy-PEP group vs 139 (30.5%) of 455 quarters in the standard-care group, with an absolute difference of 19 percentage points and a relative risk of 0.39 (95% CI 0.31–0.49, P <0.0001). During the OLE, STIs were found in 51 (13%) of 388 quarters in the doxy-PEP group and 25 (17%) of 145 quarters in those who initiated doxy-PEP. There was 1 grade 2 laboratory abnormality and 5 grade 3 adverse events (AEs) related to doxy-PEP, with no serious adverse events (AEs) linked to doxycycline. Among those with positive gonorrhoea cultures, 8 (27%) of 29 on doxy-PEP and 5 (24%) of 21 not on doxy-PEP showed tetracycline resistance (minimum inhibitory concentration ≥2 μg/mL). 

Investigators concluded that doxy-PEP reduced bacterial STIs in men who have sex with men and transgender women, with sustained efficacy even when its effectiveness was known, and was well-tolerated with no new safety concerns. 

Source: thelancet.com/journals/laninf/article/PIIS1473-3099(25)00085-4/abstract