Australia’s national rollout of doxycycline post-exposure prophylaxis, known as doxyPEP, was associated with sustained population-level declines in syphilis and chlamydia diagnoses among gay and bisexual men, according to a new analysis of sentinel surveillance data published in Nature Health. Over the 27 months following the release of national prescribing guidance in September 2023, cumulative syphilis diagnoses were 55% lower than projected had pre-guidance trends continued, and chlamydia diagnoses were 36% lower. No significant change was observed for gonorrhoea.
The study, led by Michael Traeger and colleagues at the Burnet Institute and partner organisations, drew on the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses, or ACCESS. The researchers analysed routinely collected data from 29 sexual health services and high-caseload general practice clinics between January 2022 and December 2025. In total, 78,560 gay and bisexual men aged 16 years or older received at least one test for a bacterial sexually transmitted infection during the study period, including 68,113 tested for syphilis, 73,567 for chlamydia and 73,760 for gonorrhoea. Of these men, 27,725, or 35.3%, were diagnosed with at least one case of infectious syphilis, chlamydia or gonorrhoea over the four years, with 5,198 syphilis cases, 27,190 chlamydia cases and 27,301 gonorrhoea cases recorded overall.
The analysis divided the study window into three periods: a pre-guidance phase from January 2022 to March 2023, an evidence-dissemination phase from April to September 2023 that began with the publication of the US DoxyPEP trial results, and a post-guidance phase from October 2023 to December 2025 following release of the Australian national doxyPEP guidance. Using interrupted time-series models fitted to monthly diagnosis counts, the team found that syphilis diagnoses had been rising by 1.8% per month before guidance, then fell by 1.3% per month afterwards, a statistically significant shift in trend of 3.1 percentage points per month. Chlamydia diagnoses had been stable before guidance and declined by 2.3% per month afterwards. No significant immediate step changes were detected at either interruption point, and no significant trend change was seen for gonorrhoea.
When the researchers compared model-predicted cumulative diagnoses during the post-guidance period with a counterfactual scenario in which pre-guidance trends continued unchanged, they estimated 2,430 syphilis cases under the observed trend against 5,403 under the counterfactual, a rate ratio of 0.45. For chlamydia, the corresponding figures were 13,676 observed versus 21,280 counterfactual, a rate ratio of 0.64. For gonorrhoea, the observed estimate of 16,099 cases was slightly higher than the counterfactual projection of 14,543, a non-significant rate ratio of 1.11, indicating no measurable population-level impact on that infection.
Subgroup analyses focused on the populations prioritised in the national guidance showed even larger relative reductions for syphilis among men with a sexually transmitted infection diagnosis in the preceding 12 months, with a rate ratio of 0.36, and similar reductions among men with evidence of HIV pre-exposure prophylaxis use and men living with HIV. In every subgroup examined, cumulative gonorrhoea diagnoses remained non-significantly higher than the counterfactual projection. The authors note that these patterns are consistent with doxyPEP uptake concentrating among individuals at the highest risk of bacterial sexually transmitted infections.
Supporting evidence for increasing uptake came from exploratory prescribing analyses restricted to 16 clinics whose systems recorded prescription instructions in an analysable format. Among 15,719 unique men attending those clinics, 41,556 doxycycline prescriptions were issued during the study period, of which 6,917 contained instructions indicative of doxyPEP use, and 4,001 unique individuals received at least one such prescription. Prescriptions indicative of doxyPEP accounted for just 0.04% of doxycycline prescriptions during the pre-guidance period, rising to 1.6% during evidence dissemination and 27.7% after national guidance, and by December 2025 half of all doxycycline prescriptions at those clinics contained doxyPEP-indicative instructions.
Importantly, the observed declines in diagnoses were mirrored by trends in test positivity, which the researchers used to check whether the falls might simply reflect changes in testing volume. Positivity was stable for all three infections during the pre-guidance period, and declines in positivity were seen for syphilis and chlamydia in the periods after evidence dissemination and guidance. The authors argue that concurrent declines in both diagnoses and positivity suggest a genuine reduction in underlying incidence among men attending services in the sentinel network, although they caution that testing practices themselves may have been influenced by doxyPEP implementation.
The absence of a gonorrhoea effect stands out against the strong results for the other two infections, and the study points to antimicrobial resistance as a likely explanation. DoxyPEP effectiveness against gonorrhoea has been weaker and less consistent in trials and observational studies, probably reflecting substantial geographic variation in tetracycline susceptibility among gonococcal isolates. In Australia, tetracycline resistance has been reported to reach up to 60% of isolates in some jurisdictions, and a recent systematic review estimated median tetracycline resistance in the East Asia and Pacific region at 82.1%. The authors also note that gonorrhoea showed the poorest model fit of the three outcomes, and that observed case counts at the end of follow-up were similar to counterfactual predictions, providing no evidence of behavioural change that would be expected to increase gonorrhoea transmission.
The findings extend earlier evidence from San Francisco, where city-level analyses after that jurisdiction released doxyPEP guidelines in October 2022 also found declines in chlamydia and early syphilis notifications but not gonorrhoea. With more than two years of post-guidance follow-up, the Australian analysis suggests that population-level reductions in syphilis and chlamydia can be sustained following broad guideline implementation in a high-income setting. The authors add that the greater relative decline in syphilis may reflect the design of Australia’s guidance, which recommends considering doxyPEP for men with a recent syphilis diagnosis, multiple bacterial infections in the past 12 months or anticipated periods of heightened sexual risk, with use intended to be time limited and delivered alongside quarterly screening, HIV prevention and vaccination.
The researchers emphasise that their results reflect population-level associations following the dissemination of guidance rather than the causal effect of doxyPEP use in individuals. Because ACCESS is a sentinel surveillance system that may over-represent men engaged with sexual health services, the magnitude of the reductions may not generalise to men who do not access regular care. Transgender status was not consistently captured, individual doxyPEP exposure could not be reliably identified across the full dataset, and some men may obtain doxycycline without a prescription. Residual confounding and unmeasured behavioural changes cannot be excluded, although the authors argue that the divergent patterns across infections, with declines in syphilis and chlamydia alongside stable or rising gonorrhoea, reduce the likelihood that the findings are explained solely by secular trends. They conclude that doxyPEP is a promising complement to existing test-and-treat strategies, while stressing that the lack of a gonorrhoea decline highlights the need to pair implementation with enhanced gonorrhoea-specific prevention and control efforts.
Subject of Research: Population-level impact of doxycycline post-exposure prophylaxis on bacterial sexually transmitted infections among gay and bisexual men in Australia
Article Title: Population-level impact of doxycycline post-exposure prophylaxis on bacterial sexually transmitted infections
Article References: Traeger, M. W., Asselin, J., Aung, H. L., Carter, A., Wilkinson, A. L., Cornelisse, V. J., Heath-Paynter, D., Chow, E. P. F., Ong, J. J., Varma, R., Vujcich, D., Thng, C., McCloskey, J., Rees, T., Quinn, B., Haire, B., Hellard, M., Guy, R., & Stoové, M. A. (2026). Population-level impact of doxycycline post-exposure prophylaxis on bacterial sexually transmitted infections. Nature Health. https://doi.org/10.1038/s44360-026-00211-0
Image Credits: AI Generated
DOI: 10.1038/s44360-026-00211-0
Keywords: doxyPEP, doxycycline, sexually transmitted infections, syphilis, chlamydia, gonorrhoea, gay and bisexual men, Australia, surveillance, interrupted time-series, antimicrobial resistance, public health
News Source: Ophelia Keating. (October 28, 2026). Doxycycline PEP linked to sharp drops in syphilis and chlamydia across Australia. Scienmag.
