Position statement on doxycycline post-exposure prophylaxis for the prevention of bacterial sexually transmissible infections in Aotearoa New Zealand: the New Zealand Sexual Health Society
Julia Scott
A B , Massimo Giola A C and Jeannie Oliphant A D *
A
B
C
D
Abstract
Recent studies have demonstrated that doxycycline post-exposure prophylaxis (doxy-PEP) reduces the risk of syphilis and chlamydia in men who have sex with men and transgender women who have sex with men who are at risk of sexually transmitted infections (STIs). With several international organisations publishing guidance regarding doxy-PEP use, and substantial community and sector interest, the New Zealand Sexual Health Society drafted an interim statement and then convened a cross-sectoral meeting to discuss doxy-PEP benefits and risks, and review and revise the statement. There was strong agreement that doxy-PEP be considered as part of a comprehensive STI prevention approach to people assigned male sex at birth who have sex with men who are at risk of syphilis, primarily as an intervention to prevent syphilis. New Zealand Sexual Health Society advises that doxy-PEP be proactively offered to people assigned male sex at birth who have sex with men with a diagnosis of syphilis or two other bacterial STIs in the past 12 months, and considered for others as outlined in the statement. Prescription of doxy-PEP should include counselling on the benefits and harms including side-effects and antimicrobial resistance, with users assisted to maximise the benefits of doxy-PEP while minimising overall antibiotic use. STI diagnostic considerations, and monitoring and surveillance are discussed.
Keywords: doxycycline, New Zealand, prevention, STIs, syphilis.
Introduction
Bacterial sexually transmitted infections (STIs) have been rising in Aotearoa New Zealand for many years, with a particularly sharp increase in syphilis and gonorrhoea since 2022. Gay, bisexual and other men who have sex with men (MSM), Māori and Pacific people, and young people are inequitably affected.1
Doxycycline post-exposure prophylaxis (doxy-PEP) is a new biomedical STI prevention tool that involves taking 200 mg oral doxycycline within 72 h after condomless sex to reduce the risk of a bacterial STI. Three randomised controlled trials among cisgender MSM and transgender women who have sex with men at risk of bacterial STIs have shown a relative risk reduction of 70–80% for syphilis and 70–90% for chlamydia in those randomised to take a single dose of 200 mg doxycycline within 72 h after a possible exposure.2–4 These studies showed variable efficacy of doxy-PEP against gonorrhoea, from no significant reduction observed in one study, to up to 57% reduction in another, likely due to geographical differences in levels of tetracycline-resistant gonorrhoea. One randomised controlled trial in cisgender women in Kenya on PrEP found doxy-PEP was not effective for bacterial STI prevention in this population.5 These findings have been attributed to low adherence in this cohort,5 and trials among cisgender women are ongoing. Several international organisations, including the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM), the United States Centers for Disease Control and Prevention, the British Association for Sexual Health and HIV, and State authorities in North America, have issued guidance regarding doxy-PEP use.6–10
Concerns have been raised regarding the potential for doxy-PEP to introduce a selection pressure for antimicrobial resistance (AMR) in Neisseria gonorrhoeae and other organisms; for example, leading to cross-resistance to antimicrobials used for the treatment of gonorrhoea.11
The New Zealand Sexual Health Society (NZSHS) is a group of professionals working or interested in the field of sexual health in Aotearoa New Zealand. Membership is multidisciplinary, and includes doctors, nurses, counsellors, researchers, educators, health promoters and others in public health with an interest in sexual and reproductive health. NZSHS is responsible for STI guideline development and review, national conference convening, and undertakes education and advocacy.
NZSHS believes that the epidemics of STIs in Aotearoa New Zealand can be controlled, similar to the most recent trends of the HIV epidemic, by implementing a comprehensive STI prevention approach. Drawing on the Consensus Statement on Comprehensive HIV Prevention in Aotearoa New Zealand,12 and Aotearoa New Zealand Sexually Transmitted and Blood Borne Infection Strategy 2023–2030,13 NZSHS defines comprehensive STI prevention as using a range of evidence-informed behavioural, biomedical and structural STI prevention approaches strategically, simultaneously and at scale, tailored to specific needs of individuals and communities, and responsive to developments and innovations in epidemiology, pharmaceutical and non-pharmaceutical interventions.
NZSHS initiated a process of consensus building to inform a statement on doxy-PEP. This was initially planned to form part of a wider statement on comprehensive STI prevention. However, given the emerging evidence for doxy-PEP, marked interest in the sector and community, and the limited impact with existing resources available for case detection, treatment and contact tracing on the syphilis epidemic in Aotearoa New Zealand, NZSHS initially sought discussion and agreement on a standalone doxy-PEP statement.
Methods
Two co-authors drafted an interim statement, and circulated this to NZSHS members and other key sexual health stakeholders, as well as representatives from ASHM. NZSHS then convened a half-day meeting, with the support of ASHM, on 16 February 2024. The meeting was opened and closed by the NZSHS executive president, and co-chaired by the interim statement authors. The meeting was attended by community organisation representatives, sexual health clinicians, researchers, and experts in public health, epidemiology, microbiology and infectious diseases.
Two expert presentations on evidence for doxy-PEP and international statements and guidelines, and on AMR and doxy-PEP were followed by a discussion on support for, concerns and questions regarding doxy-PEP, and reviewing and seeking support for each specific component of the interim statement. One co-chair provided a summary of the discussion at the end of the meeting, and then NZSHS circulated a revised statement. Participants were asked to indicate if they did not agree with the statement, or raise further concerns, which were discussed via email. One participant did not support the statement and asked that their name be removed from the list of attendees at the meeting. The final statement was published on the NZSHS website, and sexual health clinics have since developed their own guidelines based on the statement.
Key points of discussion
Evidence for doxy-PEP
Although there is good evidence that doxy-PEP reduces the risk of syphilis and chlamydia in MSM at an individual level in the short term, the long-term benefits and risks are unknown; including potential impacts on AMR in STIs, such as N. gonorrhoeae and Mycoplasma genitalium, and in other bacterial species, such as Staphylococcus aureus. Participants agreed on the need for the statement to state this uncertainty. Given the most serious infection for individuals is syphilis, the statement should emphasise that doxy-PEP is primarily for syphilis prevention. There is currently no clinical trial evidence for efficacy of doxy-PEP in STI prevention for cisgender women.
Demand for doxy-PEP
Participants thought that there had not been a marked observed increase in demand for doxy-PEP since the Australian consensus statement was published beyond the substantial interest, which was already apparent due to international studies and media. In NZ, there has been interest in doxy-PEP expressed by the community, to community organisations and some sexual health services. Some general practitioners in NZ are already prescribing doxy-PEP, and increasingly, clinicians are likely to be asked about it, so there is a need for guidance to ensure that benefits are maximised while adverse impacts are minimised.
Implementation of doxy-PEP
Some participants thought that doxy-PEP should be implemented as a demonstration or evidence gathering project in sexual health clinics before being rolled out to primary care. Others expressed concern that many people do not have access to sexual health clinics and this may mean withholding an effective intervention for some people. Also, as people are already accessing doxy-PEP, in the absence of a statement or recommendations, this may not be happening in a way that maximises benefits and minimises risks. Although the evidence is evolving, there is a need for a pragmatic response. There was general agreement on the need to publish a statement, and then gather NZ evidence through a sexual health clinic audit of doxy-PEP use, impact and side-effects, and national surveillance data to inform future statements and guidelines.
Suitability criteria
Participants thought it important to include behavioural suitability criteria in addition to a history of syphilis or two other bacterial STIs in the past 12 months, because not only those with past infections are at risk of syphilis and could benefit from doxy-PEP. Community members reported frustration with having to put themselves at risk of HIV to be eligible for PrEP under previous special authority criteria for prescription, and as doxy-PEP reduces STI acquisition, those on doxy-PEP may no longer fit past infection criteria while remaining at risk.
Participants discussed equity considerations, and agreed on specific consideration of doxy-PEP for Māori and Pacific MSM, given inequities in syphilis for these populations and for MSM who also have sexual partners with a uterus, given the impact of chlamydia, gonorrhoea and syphilis for these people, and the potential for doxy-PEP to contribute to prevention of syphilis in pregnancy and congenital syphilis.
Prescribing guidance
Participants discussed how to best support reasonable use of doxy-PEP. Points included the need for discussion and shared decision-making with clients, reviewing the ongoing suitability for doxy-PEP at each visit, and providing guidance on how to effectively limit use, such as taking a single dose at the end of a weekend, if consistent with timing of risk. Participants agreed on clear guidance for a prescription for clinicians, a recommended maximum of 72 100 mg tabs, which equates to three doses per week for 12 weeks.
Participants agreed on the need for ongoing comprehensive 3-monthly screening for all three bacterial STIs in people taking doxy-PEP.
Although some participants were concerned about the potential impact on population-level AMR, others considered the impact likely to be low given the already widespread long-term use of doxycycline for other indications, and the relatively small population who will take doxy-PEP.
Interpretation of syphilis serology in context of doxy-PEP
Because doxycycline is active against Treponema pallidum, there is a concern that the serological response to infection will be attenuated and, therefore, difficult to interpret, in people taking doxy-PEP. Participants agreed on the need for a low threshold for treating people taking doxy-PEP with any reactive serology, and discussed approaches to contact tracing if an index taking doxy-PEP has a suspected attenuated response. There is currently no evidence to inform management in this situation, and it was agreed to advise clinicians to discuss any reactive serology in someone taking doxy-PEP with a sexual health physician. Another concern raised was potential impact on surveillance of infectious syphilis, if cases taking doxy-PEP do not meet the surveillance case definition due to an attenuated response. This could be monitored at a national level if clinicians notify suspected cases, and doxy-PEP use is added to case report forms.
Management of STI contacts taking doxy-PEP
Participants agreed that although doxy-PEP provides protection against syphilis to individuals, given its potential impact, people taking doxy-PEP presenting as contacts of syphilis in the window period should be treated. Because tetracycline resistance among gonococcal isolates in NZ is high (12% susceptible in 2023),14 participants did not expect doxy-PEP to protect against gonorrhoea, and therefore, people taking doxy-PEP presenting as contacts of gonorrhoea in the window period should be managed in the same way as other contacts of gonorrhoea who are not taking doxy-PEP, according to current guidelines. Given the high efficacy in protection from chlamydia and the lower clinical impacts of chlamydia in MSM, participants thought people taking doxy-PEP presenting as contacts of chlamydia within the window period could either be treated or retested outside the window period after discussion between clinician and client.
Impact on health system of doxy-PEP implementation
Participants acknowledged potential impacts on clinical workload in sexual health and primary care clinics if there were widespread rapid uptake of doxy-PEP. This has not been the case in Australia, however, and some participants noted that often doxy-PEP would be discussed in a PrEP consultation or STI treatment consultation, and may not have a marked impact on workload.
Measuring impacts and consequences
Participants agreed on the need to monitor doxy-PEP prescription, impacts in terms of STIs, and AMR at an individual and population level. There was discussion on how to achieve this, with suggestions including sexual health clinics coding and then auditing doxy-PEP prescribing, incident STIs and gonorrhoea AMR, and including doxy-PEP information in national surveillance. Infectious syphilis and gonorrhoea are notifiable, with the Institute of Environmental Sciences and Research monitoring and reporting case numbers and rates on behalf of the Ministry of Health. All agreed on the need to ensure people taking doxy-PEP who acquire gonorrhoea infection have a culture swab for antimicrobial susceptibility testing, and noted that there will need to be engagement with laboratories to ensure this is possible from general practice as well as sexual health.
Discussion
The New Zealand Sexual Health Society position statement recommends that doxy-PEP be considered as part of a comprehensive STI prevention approach, primarily as an intervention to prevent syphilis, for MSM and other people assigned male sex at birth who have sex with men who are at risk of syphilis (Table 1). Although there is good evidence that doxy-PEP reduces the risk of syphilis and chlamydia in this population in the short term, NZSHS also notes that the long-term benefits and risks including impacts on AMR are unknown. Therefore, the statement outlines initial recommendations for prescribing to maximise benefits while minimising overall antibiotic use, ensuring STIs are detected and managed appropriately, and for monitoring and surveillance at individual and community levels.
| When to consider doxy-PEP | NZSHS recommends considering doxy-PEP, primarily as an intervention to prevent syphilis, to people assigned male sex at birth who have sex with men who are at risk of syphilis with the following suitability criteria: Proactively discussing doxy-PEP with people assigned male sex at birth who have sex with men with a diagnosis of syphilis or two other bacterial STIs (i.e. gonorrhoea, chlamydia) during the previous 12 months; Considering doxy-PEP for people assigned male sex at birth who have sex with men who identify an upcoming period of heightened STI risk; for example, attendance at a sex event, or holiday plans that likely involve sexual activity with multiple casual sexual partners; Considering doxy-PEP for people assigned male sex at birth who have sex with men with concurrent male and cisgender female sexual partners or other sexual partners with a uterus, recognising the additional health risks posed by chlamydia, gonorrhoea and syphilis for people with a uterus; Considering doxy-PEP for all people assigned male sex at birth who have sex with men who are Māori or Pasifika, given inequities in syphilis for these populations. | |
| How to prescribe doxy-PEP | NZSHS recommends than prescription of doxy-PEP should be undertaken in the context of comprehensive sexual health care, and with counselling on the benefits and harms including side-effects and antimicrobial resistance; People who use doxy-PEP should be assisted to maximise the benefits of doxy-PEP while minimising overall antibiotic use. For example, if someone taking doxy-PEP tends to have multiple sexual partners during weekends, a single Monday morning dose of 200 mg doxy-PEP should adequately cover their STI risk, rather than multiple doses over the weekend; The recommended maximum amount of doxycycline prescribed for each 3-month period should not exceed 72 × 100 mg tabs, which equates to three doses per week for 12 weeks; People who use doxy-PEP should have or continue to have frequent STI checks (every 3 months) including multisite chlamydia and gonorrhoea and HIV/syphilis testing; The need for ongoing doxy-PEP should be reviewed at each follow up visit. | |
| STI diagnostic considerations | Every time gonorrhoea is diagnosed in someone who reports recent doxy-PEP use, an additional swab for culture and antibiotic susceptibilities should be requested for surveillance purposes; If someone who reports recent doxy-PEP use presents as a contact of syphilis or gonorrhoea they should be treated as a contact if within the window period for infection according to current guidelines. If they present as a contact of chlamydia, re-testing outside the window period rather than presumptively treating is recommended; Doxy-PEP may result in an attenuated syphilis serological response, therefore any reactive syphilis serology (including EIA only) in someone who reports recent doxy-PEP use should be discussed with a sexual health physician. | |
| Monitoring and surveillance of doxy-PEP in Aotearoa New Zealand | NZSHS recommends: Monitoring the amount of antibiotic used by people taking doxy-PEP at an individual level; Surveillance of AMR in organisms of concern, including Neisseria gonorrhoeae, Mycoplasma genitalium, Staphylococcus aureus; Considering how to assess the impact of doxy-PEP on STI incidence including considerations of equity of access and impact (ethnicity, geography). |
This statement is in line with statements and guidelines from some international organisations. The Australian consensus statement on doxycycline post-exposure prophylaxis likewise recommends doxy-PEP be considered primarily for the prevention of syphilis in gay, bisexual and other MSM at risk of this STI, with suitability criteria including a diagnosis of syphilis or two or more other bacterial STIs in the prior 12 months.6 The United States Centers for Disease Control and Prevention Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis recommends providers offer all MSM and transgender women with a history of at least one bacterial STI in the prior 12 months through shared decision-making.7 By contrast, doxy-PEP is currently not endorsed by the British Association for Sexual Health and HIV or the United Kingdom Health Security Agency.15
This process of position statement development included experts from a variety of fields relevant to doxy-PEP, and representatives from community organisations working with people experiencing an inequitable burden of STIs. There was generally very strong support from this diverse range of experts for the use of doxy-PEP, as outlined in the position statement.
Since this statement was published, sexual health services in Aotearoa New Zealand have developed clinic guidelines and procedures to support doxy-PEP prescribing based on the statement, with specific clinic codes created to facilitate monitoring of uptake of doxy-PEP within these services. NZSHS representatives are currently working with a primary care guideline group to produce guidance on doxy-PEP tailored to general practitioners and other primary care prescribers, to ensure communities have appropriate access to doxy-PEP in a variety of settings, including areas not served by specialist sexual health clinics.
Data availability
Data sharing is not applicable, as no new data were generated or analysed during this study.
Acknowledgements
NZSHS thanks A/Prof Vincent Cornelisse, Sexual Health Physician and Researcher; NSW Health; The Kirby Institute, UNSW Sydne; and Ben Riley, Policy and Public Affairs Manager, ASHM, for their assistance in organising and convening the meeting.
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