Technical information: Doxycycline post-exposure prophylaxis for sexually transmitted infections prevention
This page provides technical information supporting the WHO guideline on the use of doxycycline post-exposure prophylaxis (PEP) for the prevention of bacterial sexually transmitted infections (STIs) among men who have sex with men and transgender women. Doxycycline PEP involves taking a single dose of 200mg of doxycycline within 72 hours of condomless sex to prevent bacterial STIs. This page does not replace the full WHO guideline, which will be published within the coming months.
Global context
Bacterial STIs, including Treponema pallidum (syphilis), Chlamydia trachomatis and Neisseria gonorrhoeae, continue to impose a substantial global public health burden, with incidence rising in many settings and limited new prevention options available.
Doxycycline PEP has emerged as a potential biomedical prevention strategy for certain populations following sexual exposure, building on evidence from randomised trials conducted among populations disproportionally affected by STIs.
This guideline provides recommendation on the use of doxycycline PEP for the prevention of STIs among men who have sex with men and transgender women, populations disproportionately affected by STIs. At present, WHO does not recommend doxycycline PEP for other populations, nor the use of doxycycline as pre-exposure prophylaxis (PrEP); guidance in these areas may be developed as additional evidence becomes available.
(Conditional recommendation; moderate certainty of evidence)
Key considerations
- Doxycycline PEP should be provided as part of a comprehensive sexual health approach, complementing other prevention strategies such as condom use.
- Men who have sex with men and transgender women with recent or recurrent STI – especially syphilis – and those in high-incidence sexual networks or settings should be prioritized.
- Context-appropriate monitoring of antimicrobial resistance (AMR) is strongly encouraged as part of doxycycline PEP policy. Ideally, trends in both AMR and antibiotic use should be monitored.
Overview of the evidence and guideline judgements
This section provides information on effectiveness; safety and tolerability; antimicrobial resistance; balance of benefits and harms; values, preferences and acceptability; resource requirements; equity; and acceptability.
Effectiveness
Randomised clinical trials have demonstrated that doxycycline PEP substantially reduces the incidence of syphilis (RR 0.20; 95% CI 0.11-0.37, high certainty) and chlamydia (RR 0.15; 95% CI 0.10-0.23, high certainty) among men who have sex with men and transgender women compared with no doxycycline PEP. Reductions in gonorrhoea have been observed (RR 0.52; 95% CI 0.40-0.68; moderate certainty); however, effectiveness is inconsistent across settings and depends on local levels of tetracycline resistance in circulating N. gonorrhoeae strains. The Guideline Development Group (GDG) considered the strong preventive effect against syphilis the most valuable given the pathogenesis of the infection, gaps in clinical care, and its health impact.
Safety and tolerability
Doxycycline is a widely used antibiotic with a well-characterized safety profile. Across trials, doxycycline PEP was generally well tolerated, with gastrointestinal symptoms being the most commonly reported adverse effect. Serious adverse events attributable to doxycycline were rare and similar among users and non-users.
Antimicrobial resistance
Potential impacts on antimicrobial resistance (AMR) were a central consideration in the guideline deliberations but evidence is uncertain. Overall, the certainty of any evidence of the impact of doxycycline PEP on AMR is classified as low – and in most cases as very low – due to studies that have small sample size, vary in design, are prone to selection bias, and include different pathogens. AMR among C. trachomatis or T. pallidum has not been demonstrated. Evidence points towards selection for resistance to tetracyclines in N. gonorrhoeae, other pathogens and the microbiome. However, the GDG considered the extent of this selection and its public health impact remain uncertain, particularly due to inadequate data and differences in circulating background prevalence of tetracycline resistance in N. gonorrhoeae and other pathogens in different populations.
Balance of benefits and harms
The GDG judged that, for the recommended populations, the public health benefits of preventing syphilis and chlamydia outweigh the potential risks, provided that doxycycline PEP is delivered within a comprehensive STI prevention package and is accompanied by antimicrobial stewardship measures.
Values, preferences and acceptability
Qualitative evidence indicates high acceptability of doxycycline PEP among men who have sex with men and transgender women at increased risk of STIs, particularly when integrated into existing sexual health services. Doxycycline PEP users emphasized the importance of autonomy, choice, confidentiality and access to clear information about benefits and risks.
Resource requirements
Doxycycline is inexpensive and widely available, but additional costs may result from service integration, provider training and programme implementation, particularly in resource-limited settings. Long-term costs related to potential effects of AMR remain unknown but may be partially offset by savings resulting from reductions in the diagnosis and treatment of symptomatic bacterial STIs. The GDG judged the resource requirements to be uncertain and highly context-specific.
Equity
The GDG considered that the availability of formal WHO guidance on doxycycline PEP would likely improve equity by strengthening trust and service provision between health systems, providers and affected communities. Clear guidance could facilitate access to quality-assured drugs and services and reduce reliance on informal and unregulated access channels.
Acceptability
Evidence on acceptability is limited to studies from the United States of America and one from Brazil, and perspectives may vary globally. Nevertheless, informed by findings from the WHO global community consultation, the GDG judged that doxycycline PEP for STI prevention would probably be acceptable to most key stakeholders globally. Acceptability was considered high among users and affected communities, generally acceptable among service providers and public health practitioners (despite some concerns related to AMR) and more limited among microbiologists.
Implementation considerations and research gaps
The following considerations summarize key technical issues for implementation; detailed guidance will be provided in the full WHO guideline. This section contains information on target population and prioritization; dosing and use; integration with existing services; antimicrobial stewardship and surveillance; equity and access; and research gaps.
Target population and prioritization
Doxycycline PEP should be prioritized for men who have sex with men and transgender women with a recent bacterial STI – particularly syphilis – and ongoing risk of exposure and those in high-incidence sexual networks or settings. Periodic reassessment of eligibility should be conducted. Programmes should avoid population-wide use and focus on individuals most likely to benefit.
Dosing and use
Doxycycline PEP is taken as a single 200mg oral dose ideally within 24 hours, and no later than 72 hours, after condomless sex. Use should be event-driven and repeat dosing within a 24-hour period should be avoided to reduce risks of adverse events. Some people may effectively transition along a continuum between doxycycline pre- and post-exposure prophylaxis. There is currently no evidence to support daily use, and WHO does not currently recommend doxycycline for PrEP.
Integration with existing services
Doxycycline PEP should be integrated within comprehensive sexual health services, including regular STI testing, HIV prevention and care, risk-reduction counselling and condom access. It complements but does not replace other STI prevention strategies such as condom use, STI testing and partner services.
Antimicrobial stewardship and surveillance
Countries implementing doxycycline PEP should strengthen surveillance for AMR in N. gonorrhoeae and other relevant pathogens. Patterns of use should be monitored to minimize inappropriate exposure to antibiotics.
Equity and access
Implementation should consider equity, ensuring that populations most affected by STIs can access services safely and without stigma. Community engagement and clear communication are essential.
Research gaps
The GDG identified important evidence gaps, including the long-term effects of doxycycline PEP on AMR, impacts on the microbiome, effectiveness in different epidemiological settings, and potential use in other populations. Ongoing and future studies will be critical to inform updates to the recommendation.
Summary of guideline development process
The guideline was developed in accordance with the methods outlined in the second edition of the WHO Handbook for Guideline Development. WHO convened an international GDG that reviewed the evidence and formulated recommendations through virtual meetings, with additional peer review conducted by the External Review Committee. The GDG prioritized outcomes and considered findings from systematic reviews assessing quantitative evidence (benefits and harms) and qualitative evidence (values, preferences, acceptability, feasibility and equity), including a global community consultation. Certainty of evidence was assessed using the GRADE and CERQual approaches within the evidence-to-decision framework, leading the GDG to conclude that sufficient evidence was available to issue a recommendation.