DoxyPEP halved syphilis and cut chlamydia by a third in Australian data

National Australian data published in Nature Health and reported this week in The Medical Republic shows that doxycycline post-exposure prophylaxis (doxyPEP) guidance had a large and sustained effect on syphilis and chlamydia rates among gay and bisexual men who access sexual health services and general practice. The findings are among the strongest population-level evidence for doxyPEP published to date, and they come from Australian services using Australian prescribing guidance.

For anyone working in or accessing sexual health services in Australia, this data matters. Syphilis has been in a prolonged national upward trajectory for years. A 55% reduction in estimated cases over two years is not a modest signal.

What the study found

The researchers used data from 29 sexual health and general practice services in the ACCESS network, covering January 2022 through December 2025 — a dataset of 78,560 gay and bisexual men aged 16 or over, each with at least one bacterial STI test. They applied interrupted time-series analysis across three periods: before guidance (January 2022 to March 2023), during evidence dissemination (April to September 2023), and after guidance release (October 2023 to December 2025).

The findings:

Syphilis: Diagnoses were rising at 1.8% per month before guidance. After guidance release, the trend reversed to a 1.3% fall per month. Estimated cases over the post-guidance period fell from a projected 5,403 to an observed 2,430 — a 55% reduction.

Chlamydia: Stable before guidance, then declining 2.3% per month afterwards. Estimated cases fell from a projected 21,280 to 13,676 — a 35% reduction.

Gonorrhoea: No significant change attributable to the guidance. The researchers attributed this to two factors: doxycycline is known to be less effective against gonorrhoea than against syphilis or chlamydia, and tetracycline resistance in Australian gonorrhoea isolates is high, reaching up to 60% in some jurisdictions.

Critically, testing volumes were monitored through the analysis. The declines in test positivity mirrored the case count reductions — meaning the results were not driven by fewer tests being done.

Both-and: the case for doxyPEP and the questions it opens

The evidence case is strong and unusually local. This is not a US or European trial being extrapolated. It is data from Australian services, using Australian consensus guidance, over more than two years. The researchers conclude this represents “national-level evidence of sustained reductions over more than two years in bacterial STI diagnoses” — a phrase that matters in a country that has watched syphilis rates climb for over a decade.

The ASHM consensus guidance for doxyPEP is integrated and targeted: it is not a standing prescription for everyone, but a time-limited intervention (typically three-month periods) for people meeting specific criteria, embedded in quarterly STI screening, HIV prevention through PrEP and PEP, and vaccination programs. The researchers suggest that this targeted, integrated framing may explain the stronger syphilis effect — prior modelling indicated that targeting people with recent STI diagnoses yields the greatest population benefit, which is exactly what this guidance does.

The complexity lies in what doxyPEP does not solve. Gonorrhoea — an infection with significant antibiotic resistance challenges globally — showed no benefit. That is not a failure of the guidance; it is a known limitation baked into the design. But it means the conversation with a patient about doxyPEP has to be specific: this reduces syphilis and chlamydia risk substantially if taken correctly within 72 hours; it does not reliably reduce gonorrhoea risk, and regular gonorrhoea testing remains important.

The other complexity is antimicrobial stewardship. Routine antibiotic use at scale raises legitimate concerns about resistance selection. The researchers themselves note that wider doxyPEP uptake may warrant reassessing routine asymptomatic STI screening, balancing clinical benefit against overtreatment and resistance pressure. This is not a reason to avoid doxyPEP — the data for syphilis and chlamydia is compelling — but it is a reason why the targeted, criteria-based approach in Australian guidance is designed the way it is.

What this means in a general practice consult

The ACCESS study covered not only specialist sexual health services but also general practice sites. That matters. The syphilis epidemic has long been concentrated in gay and bisexual men accessing specialist services, but it has been expanding beyond that population over the past several years. GPs are increasingly the point of contact for patients who have STI risk, want to discuss prevention options, or present with symptoms.

The RACGP provides guidance for sexual health care in general practice, including on when to discuss doxyPEP with eligible patients. For GPs who have not been systematically offering doxyPEP discussions to eligible patients — those with recent syphilis, multiple bacterial STIs in 12 months, or anticipated high-risk periods — the Australian data now gives a strong evidence basis for that conversation.

The 72-hour window matters: patients who may benefit should know about it in advance, not at the point of needing it.

2 cents

A 55% reduction in syphilis is a remarkable number for a national cohort over two years. It is the kind of effect size that rarely appears in population-level prevention data. The Australian guidance worked. The data is local, the timeframe is long enough to be credible, and the effect held.

For GPs seeing gay and bisexual male patients with sexual health risk: the conversation about doxyPEP eligibility is now better supported by Australian evidence than almost any other STI prevention tool in this cohort beyond vaccination and PrEP. If you have not had that conversation with eligible patients, the data gives clear reason to.

For patients who think they might be eligible: raise it with your GP. DoxyPEP is a prescription medication. Knowing you are eligible and understanding the 72-hour window in advance is what makes it usable.

Verdict: yes — this is robust, local, two-year data showing population-level benefit from a targeted prescribing guideline.

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Sources cited

1. DoxyPEP guidance reduces syphilis, chlamydia diagnoses — The Medical Republic, 2 November 2026
2. DoxyPEP effectiveness against bacterial STIs in Australia — Nature Health, October 2026
3. ASHM — doxyPEP consensus guidance
4. RACGP — sexual health in general practice