Doxycycline as post-exposure prophylaxis (doxy-PEP) has emerged as an efficacious strategy to reduce Chlamydia trachomatis (C. trachomatis), Neisseria gonorrhoeae (N. gonorrhoeae) and syphilis (sexually transmitted infections (STIs)) among gay, bisexual and other men who have sex with men (GBM). There is a need to identify prescribing criteria that maximise the number of STIs averted while minimising excessive use.

In this prospective longitudinal cohort study with repeated measures and biobehavioural data collection, participants completed a questionnaire and tested for STIs at each visit.

Community-based, population-level study conducted in three large Canadian cities between February 2017 and July 2023.

2449 GBM were recruited through respondent-driven sampling (RDS); 1998 had ≥1 follow-up visit, contributing 7551 person-years of observation. Eligible participants were aged ≥16 years, cis- or transgender men, reported sex with another man in the past 6 months and resided in Montreal, Toronto or Vancouver.

Adjusted rate ratios (aRR) of STIs, accounting for RDS recruitment, loss to follow-up and confounding were estimated using generalised estimating equations (GEE) Poisson regression. For identified STI risk factors, the proportions of STIs averted through doxy-PEP prescription (based on the efficacy of doxy-PEP for each bacterial STI) and the number needed to treat (NNT) for 1 year to avert one STI, assuming 100% adherence, were calculated.

Among 1998 participants, the combined incidence rate of any C. trachomatis, N. gonorrhoeae and syphilis infection was 29.5 (95%CI 27.3 to 31.9) per 100 person-years. STI risk factors that had the most impact as doxy-PEP criteria were history of any of the three STIs in the past 12 months (P12M) (aRR=2.0, 95% CI 1.8 to 2.2, 36% STI averted, NNT=2.1); ≥10 male sexual partners in the past 6 months (P6M) (aRR=3.8, 95% CI 3.0 to 4.9, 41% STI averted, NNT=2.4); HIV-pre-exposure prophylaxis (PrEP) use P6M (aRR=1.7, 95% CI 1.5 to 2.0, 29% STI averted, NNT=2.5); use of any chemsex-related substance P6M (aRR=1.2, 95% CI 1.1 to 1.4, 28% STI averted, NNT=2.6); and group sex event attendance P6M (aRR=1.2, 95% CI 1.1 to 1.3, 27% STI averted, NNT=2.3). Reporting≥10 male sex partners P6M represented the most useful criterion for syphilis prevention (52% syphilis infections averted, NNT=20). Prescribing doxy-PEP to GBM having any of the following STI risk factors, namely, ≥1 bacterial STI P12M, ≥10 male sex partners P6M, or HIV-PrEP use P6M, would substantially increase the proportion of all STI diagnoses potentially averted (60%) with minimal increase of the NNT (2.7).

This work informs on the impact of various doxy-PEP clinical prescribing criteria and demonstrates the benefit of focusing on any of the following three criteria: ≥1 bacterial STI P12M, ≥10 male sex partners P6M or HIV-PrEP use P6M.