Doxycycline and STI prevention: new guideline and perspectives
Interview with Dr Guillaume Conort, Department of General Medicine, University of Bordeaux
Last updated on 05 February 2025
The essential
The new guideline ‘Doxycycline for the prevention of bacterial sexually transmitted infections’ went online on 29 January 2025. The work is being carried out under the aegis of the ANRS MIE, the Conseil National du Sida et des hépatites virales (CNS), and the Haute Autorité de santé (HAS). In an interview, Dr Guillaume Conort, head of the working group, described the scientific rationale behind the recommendation, the efficacy and safety data available and the research required.
Why is there a specific chapter on doxycycline for the prevention of STIs?
There are several reasons for this focus. Firstly, this is an update of previous recommendations: the use of doxycycline in the prevention of sexually transmitted infections (STIs) is recent and was not taken into account in the latest recommendations of the French Society of Dermatology dating from 2016.
Secondly, this recommendation aims to evaluate an already existing practice, even though doxycycline has no official indication for prevention, and its use remains outside the scope of marketing authorisation (MA). Given the number of prescriptions that could be made, particularly as a result of new clinical trial data, it seemed necessary to carry out a rigorous analysis of the complex issues raised by this prescription, particularly as regards the possible risks and the collective implications in terms of efficacy,
What are the main efficacy studies that have supported this recommendation?
We have four main studies:
- a pre-exposure study conducted in 2011 and 2012 in Los Angeles among 30 men who have sex with men (MSM) and trans women[1]
- three post-exposure studies: a sub-study of the ANRS IPERGAY trial[2] evaluating the efficacy of HIV PrEP in multi-partner MSM in France and Canada, the DoxyPEP study[3] conducted in the USA in MSM and trans women and the ANRS DOXYVAC study, conducted in France between January 2021 and July 2022 in MSM . [4]
These studies show a reduction in the incidence of STIs with doxycycline as a preventive treatment, particularly for chlamydial infections and syphilis, and less effectiveness in preventing gonorrhoea. However, a study of women in Kenya produced disappointing results, probably due to poor compliance, which limits our ability to draw general conclusions.
[1] Bolan RK, Beymer MR, et al. Doxycycline Prophylaxis to Reduce Incident Syphilis among HIV-Infected Men Who Have Sex With Men Who Continue to Engage in High-Risk Sex: A Randomized, Controlled Pilot Study. Sex Transm Dis. 2015;42(2):98 103
[2] Molina JM, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018;18(3):308 17.
[3] Luetkemeyer AF, Donnell D, Dombrowski JC, et al; DoxyPEP Study Team. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023 Apr 6;388(14):1296-1306.
[4] Molina JM, Bercot B, Assoumou L, et al; ANRS 174 DOXYVAC Study Group. Doxycycline prophylaxis and meningococcal group B vaccine to prevent bacterial sexually transmitted infections in France (ANRS 174 DOXYVAC): a multicentre, open-label, randomised trial with a 2 × 2 factorial design. Lancet Infect Dis. 2024 Oct;24(10):1093-1104.
To date, the studies demonstrating individual efficacy of antibiotic prophylaxis against bacterial STIs with the highest levels of evidence concern a post-exposure regimen (Doxy PEP). For this reason, this is the only modality considered in this recommendation, in the population of MSM and trans women at high risk of STI.
Studies therefore show a reduction in the incidence of STIs. Are there any other benefits?
Yes, but with nuances. One important distinction concerns the differential effectiveness according to region: in Europe, levels of gonococcal resistance are higher than in the United States, which reduces the effectiveness of doxycycline against this bacterium. Furthermore, while there has been an overall reduction in the number of STIs, the impact on the epidemiological burden remains uncertain. Modelling suggests that high coverage could reduce the syphilis epidemic by 55%, but this depends on widespread adoption of treatment.
We know that doxycycline reduces the incidence of STIs in men who have sex with men and trans women. However, the impact on the overall burden of these infections is less clear. For example, the long-term complications of chlamydial infections mainly affect women, but the studies were mainly conducted in men, and the study conducted in women was inconclusive, increasing the uncertainty about the contribution of this strategy to reducing complications. This means that the contribution of this strategy to reducing long-term complications remains uncertain. In addition, the populations concerned by doxycycline are often already under regular medical supervision, which complicates the assessment of its contribution compared with a strategy of systematic screening and treatment.
We have solid evidence on the reduction in incidence, but much less on the long-term impact on public health. This uncertainty justifies a measured approach, taking into account benefits and risks at different levels. Our recommendations aim to strike a balance between these issues and to provide a framework adapted to a constantly evolving situation.
Finally, I would like to mention one last important element. I’m talking about people’s ability to have a sexuality that is better able to control the risks and the well-being associated with this control. This is an essential aspect: as a clinician, I often find that my patients on PrEP have better risk management, which contributes to their sexual fulfilment. However, this effect has been little studied and could be the subject of future research. We also need to bear in mind the burden that a positive diagnosis represents, particularly in terms of notifying partners.
What about the risks of the treatment ?
There are two main points to consider:
- Side effects of treatment
They are well known, as doxycycline has been used for a long time, both as a treatment and as a preventive measure (against malaria, for example). We therefore have extensive data on its safety. There is some uncertainty about the impact of repeated short doses, which could increase the risk of adverse effects through sensitisation. The most common side-effects are digestive (nausea, gastrointestinal problems) and not very severe, while the most worrying are skin reactions. A recent study suggests an increase in the number of cases of pigmented skin eruptions in the genital area, probably linked to the use of doxycycline to prevent STIs.
However, we lack the solid data to draw definitive conclusions. Some clinicians are reporting an increase in these reactions in their patients taking doxycycline, but more time is needed to determine whether this is a genuine warning signal or simply a statistical fluctuation. There are also drug interactions, but these remain limited.
- Antibiotic resistance remains a complex and poorly understood subject.
On the question of antibiotic resistance, we already know that gonococcus is resistant to doxycycline, but this does not directly affect the therapeutic arsenal, as this molecule is no longer used as a first-line treatment against this bacterium. For the time being, no worrying resistance signals have been observed in Chlamydia trachomatis or syphilis, although this will need to be monitored if doxycycline becomes widely used.
There are, however, concerns about cross-resistance with other bacteria in the microbiota. For the moment, there are no concrete signs of this, but there are indications that it could become a problem in the long term.
Finally, from a more general point of view, the trend is to reduce antibiotic consumption in order to limit the emergence of resistance. However, using an antibiotic for prevention, i.e. without being ill, goes against the general recommendations for antibiotic therapy.
Can you outline the key points of the recommendation?
The recommendations we have put forward may seem to fall somewhere between several positions, but they are in line with those of other European countries that share our concerns about the overuse of this treatment.
- In cisgender women, the data do not support its use, so we do not recommend doxycycline for the prevention of STIs
- In men who have sex with men (MSM) and transgender women, populations on which studies have focused, we do not recommend its widespread use either. The potential benefit is considered too limited given the uncertainties. However, given the existing efficacy data, doxycycline could be offered as part of a shared decision-making process with patients, particularly those at high risk of STIs. The idea is to assess the benefits and risks with each patient before deciding on a prescription.
This targeted prescription is based on “expert agreement” (EA): while the data on efficacy in reducing the incidence of STIs are robust, we still lack the hindsight to assess the impact of large-scale use. This justifies its classification as an “expert agreement”.
In practice:
- cis men and trans women who have had sex with at least two partners in the last 12 months and who have had at least two STI episodes in the last 12 months are at high risk of STIs
- For prevention, doxycycline should be taken as a single oral dose of 200 mg as soon as possible after sexual intercourse without a condom, and for up to 72 hours, without exceeding 3 doses per week.
We do not recommend its widespread use, but envisage targeted prescribing in specific cases, with clear information for the patient on the existing uncertainties.
What are the research prospects following this recommendation?
There are many prospects, and the current recommendations are only a starting point. Future monitoring and studies will enable these strategies to be refined. The idea is to continuously assess the impact of this recommendation, both on the evolution of the epidemic and on the emergence of resistance. This will require increased vigilance and rigorous monitoring of the patients concerned. These recommendations are part of an overall prevention approach, which includes PrEP, vaccination and regular monitoring of patients: each measure has its importance and must be part of an overall prevention and risk-reduction approach.
Finally, a number of points need to be studied in greater depth. Firstly, an assessment of the effectiveness and safety of this approach in women, who are still the most affected by certain sexually transmitted infections, and secondly, a more detailed study of the behavioural impact of this prevention strategy in high-risk populations. And these studies will require collaboration between several teams to guarantee solid results that can be applied on a large scale.
Access all the guidelines (in french)
To consult all the documents available for each chapter (argument, guidelines, summary sheet, patient information sheet), go to our ‘ Expertise and Publications ’ section or the HAS and CNS websites.
CNS HAS ANRS MIE Reports and Publications
CROI 2025: accepted research projects supported by ANRS MIE
CROI, the international Conference on Retroviruses and Opportunistic Infections, will be held from March 9 to 12 in San Francisco. Around 20 projects supported by ANRS MIE have been accepted.
10 March 2025