New Australian research suggests disseminating evidence and clinical guidance regarding the use of doxycycline post-exposure prophylaxis has significantly reduced the rate of syphilis and chlamydia in gay and bisexual men.
For the first time, research has linked doxyPEP guidance with ongoing reductions in syphilis and chlamydia diagnoses among gay and bisexual men.
Australia saw significant increases in bacterial sextually transmitted infections between 2015 and 2024, meaning the development and implementation of doxycycline post-exposure prophylaxis (doxyPEP) in late 2023 came at just the right time. While international researchers have conducted single-jurisdiction studies using local surveillance data, there has yet to be a national-level examination of the impact of disseminating evidence and guidelines for doxyPEP in Australia.
“This study provides national-level evidence of sustained reductions over more than two years in bacterial STI diagnoses following the release of doxyPEP guidance, extending findings from clinical trials and early local evaluations to real-world population outcomes,” the researchers wrote in Nature Health.
STI diagnosis data from gay and bisexual men aged ≥16 years were collected from 29 sexual health and general practice services that participated in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance of Sexually Transmissible Infections and Blood Borne Viruses (ACCESS) between January 2022 and December 2025.
A total of 78,560 gay and bisexual men had at least one test for any bacterial STI during the study period, with 68,113 men undergoing at least one syphilis test, 73,567 with at least one chlamydia test, and 73,760 with at least one gonorrhoea test.
Approximately one in three men (n = 27,725, 35.3%) tested positive for at least one case of syphilis, chlamydia, or gonorrhoea. The average number of diagnoses among this cohort of men was 2.15, and the average age at time of first STI diagnosis during the study was 37.0 years. Gonorrhoea accounted for the largest number of positive test results (27,301), just ahead of chlamydia (27,190). A smaller number of syphilis cases were recorded (5198).
The researchers used interrupted time-series analyses to explore changes in monthly STI diagnoses in three distinct periods: preguidance (January 2022 to March 2023), evidence dissemination coordinated by the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (April to September 2023), and postguidance (October 2023 to December 2025). The primary analysis compared diagnosis rates during the preguidance and postguidance periods.
Syphilis diagnoses increased during the preguidance period at a rate of 1.8% per month (95% confidence interval 0.1% to 3.6%) but decreased by 1.3% per month (-2.0% to -0.6%) during the postguidance period, corresponding to an absolute reduction of -3.1 percentage points per month (-5.0 to -1.2).
Chlamydia diagnoses were stable during the preguidance period (0.9% increase per month, -0.6% to 2.3%) before declining by -2.3% per month (-2.9% to -1.7%), corresponding to a reduction of 3.2 percentage points between the two periods (-4.7 to -1.6).
Gonorrhoea diagnoses were also stable during the preguidance period (0.2% increase per month, -1.4% to 1.8%), and although there was a decrease in diagnoses during the postguidance period (-1.0% per month, -1.7% to -0.4%), there was no difference in the rate following the dissemination of the doxyPEP guidelines (-1.2 percentage points per month, -2.9 to 0.6).
The implementation of the doxyPEP guidelines was estimated to reduce the number of syphilis diagnoses from 5403 to 2430 and the number of chlamydia diagnoses from 21,280 to 13,676 compared to a world where the guidelines were not released. This translates to a 55% reduction in the rate of syphilis cases (rate ratio 0.45, 0.35-0.55) and a 35.3% reduction in the rate of chlamydia cases (0.64, 0.45 to 0.84).
“In this analysis, trends in test positivity closely mirrored patterns observed in case counts, supporting the interpretation that observed reductions in syphilis and chlamydia were unlikely to be driven solely by changes in testing volume over time,” the researchers noted.
In contrast, the estimated number of gonorrhoea cases during the postguidance period were 16,099, a slight but non-significant increase from the estimated 14,543 cases that would have occurred in the absence of the doxyPEP guidelines.
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The larger declines in syphilis diagnoses compared to chlamydia may reflect how Australia’s doxyPEP guidance was designed, according to the researchers.
“The ASHM DoxyPEP Consensus Statement recommends that clinicians consider doxyPEP for GBM and other men who have sex with men with a recent syphilis diagnosis, multiple bacterial STIs in the past 12 months, or anticipated periods of heightened sexual risk, such as travel or attendance at sex-on-premises venues. Use is intended to be time limited, typically over three-month periods, with regular clinical review,” they said.
“Importantly, the guidance emphasises that doxyPEP should be delivered within comprehensive sexual health care, including quarterly STI screening, HIV prevention (including HIV PrEP and PEP), and vaccination. Prior modelling suggests that targeting doxyPEP use to individuals with a recent STI may yield the greatest population-level reductions in subsequent syphilis infections.
“Framing doxyPEP as a targeted, timelimited intervention integrated with routine care may have facilitated early uptake among individuals at the highest risk of syphilis, contributing to the temporal patterns observed in this analysis.”
The researchers felt the lack of impact of the doxyPEP guidelines on gonorrhoea diagnoses was consistent with previous research that doxyPEP was less effective against gonorrhoea compared to syphilis and chlamydia. They also felt that the findings reflected substantial geographic variation in tetracycline susceptibility across the country.
“In Australia, tetracycline resistance among isolates has been reported to reach up to 60% in some jurisdictions. A recent systematic review reported increasing global tetracycline resistance in gonorrhoea, with the median resistance in the East Asia and Pacific region estimated at 82.1%,” they said.
The current findings have implications for future policy discussions about the optimal role of asymptomatic screening for bacterial STIs among gay and bisexual men using doxyPEP, according to the researchers.
“There is growing debate regarding the benefits and potential harms of routine asymptomatic screening for chlamydia and gonorrhoea among gay men, particularly considering the generally low risk of severe health sequelae for these infections in men without female partners and concerns about overtreatment and antimicrobial resistance,” they wrote.
“In settings where biomedical prevention strategies such as doxyPEP are widely implemented, it may be appropriate to reassess the balance between screening intensity and clinical benefit. Future STI control strategies and clinical guidelines should consider how biomedical prevention and screening interact, with an emphasis on ongoing monitoring and adaptive approaches that maximize public health impact while minimising unintended consequences.”
The researchers noted that their findings may not generalise to gay and bisexual men who do not access sexual health care on a regular basis. In addition, the fact that transexual status was not consistently recorded across participating services meant the researchers were unable to compare the impact of doxyPEP and the dissemination of guidelines between cisgender and transgender individuals. The current analyses were also unable to account for people who obtained doxyPEP without a prescription.
Regardless of these limitations, the researchers concluded that doxyPEP was an effective population-level STI prevention strategy when integrated with comprehensive sexual health services.
“These findings highlight doxyPEP as a promising complement to existing test-and-treat strategies and suggest that biomedical STI prevention interventions may play an important role in addressing rising STI trends in high-income settings,” they wrote.
