Modelling shows doxyPEP could account for 1.9% of doxycycline use in Europe

Researchers have estimated that doxyPEP use could represent 4.4 million defined daily doses (DDDs) of doxycycline being taken in Europe annually. This is equivalent to a 1.9% of total doxycycline consumption compared to 2023 levels. Understanding the impact that doxyPEP has on antibiotic usage, as well as STI rates and any antibiotic resistance, is crucial for assessing the risks and benefits of doxycycline as post-exposure prophylaxis. 

Studies have shown that doxyPEP is extremely effective at reducing rates of chlamydia and syphilis, which have been climbing in Europe over the past ten years. Doxycycline is also used for respiratory and urinary tract infections, acne, and as malaria prophylaxis. 

Since 2023, multiple European countries have written position statements or guidelines around the use of doxyPEP. Rather than broad rollouts, these announcements have generally recommended that doxyPEP is considered on a case-by-case basis for those at high risk of certain bacterial STIs, particularly syphilis. One concern regarding increased antibiotic usage is antimicrobial resistance, and initial studies have suggested that bacteria sampled from doxyPEP users could have a higher level of doxycycline resistance. However, increased antibiotic use does not necessarily lead to clinically significant increases in resistance. Furthermore, as a preventative intervention, doxyPEP could reduce the number of antibiotic courses needed to treat STIs.

The study

The study sought to quantify doxyPEP usage in Europe. Producing such an estimate is difficult as there is a lack of reliable data on how many people take it, and how often. Researchers focused on doxyPEP use among gay, bisexual and other men who have sex with men who take PrEP. This is because PrEP users are probably a large proportion (but not all) of doxyPEP users at the moment, and the number of PrEP users can be estimated from survey data.

Experts working in sexual health were asked to estimate what proportion of PrEP users take doxyPEP, and how many courses each user would take over six months. Respondents were also asked about uncertainty in their estimates – for example, as well as their best guess, they were asked what they believed the plausible upper and lower limits of doxyPEP uptake and frequency were. 

The compiled values were then fed into a Monte Carlo simulation, a way of modelling outcomes where multiple factors are uncertain. The three variables were the number of PrEP users, the proportion who use doxyPEP and how much doxyPEP each user takes. The model was run 10,000 times, with randomly sampled values from each of the three variables’ probability distributions, to estimate total doxycycline use.

Estimates were also made regarding the number of chlamydia infections avoided due to doxyPEP use, with full courses of doxycycline for these avoided infections subtracted from the final total. As syphilis is most commonly treated with benzathine penicillin rather than doxycycline, preventing syphilis would not produce the same reduction in doxycycline use. Instead, they compared estimates of doxyPEP use with syphilis prevalence among PrEP users, to provide context for the scale of antibiotic use.

Results

Researchers quantified doxycycline use as a result of doxyPEP in defined daily doses (DDDs), a World Health Organization measure that gives the average daily dose of a drug when it is used for its main indication. For doxycycline this is 100 mg once per day; however, doxyPEP is usually taken as a single 200 mg dose in the 72 hours after condomless sex (therefore 2 DDDs per standard doxyPEP course). 

Experts working in sexual health estimated that 33% of PrEP users are taking doxyPEP, an average of 24 times a year. The uncertainty in these estimates was recognised by each estimate being given a credible interval (the range within which 95% of values are expected to lie). The credible interval of PrEP users taking doxyPEP was 5-76%, while the credible interval of frequency of use was 8-54 times per year. 

After running the simulations, they found the median net annual doxycycline consumption attributable to doxyPEP was 4.4 million DDDs, after accounting for a median of 326,151 DDDs avoided through fewer chlamydia infections. This corresponds to 1.9% of total doxycycline antibiotic use in Europe in 2023.

The credible intervals were wide. Researchers estimated that there was a 95% probability that doxycycline consumption attributable to doxyPEP lies between an additional 0.5 million and 18.1 million DDDs. 

When understanding how estimated doxycycline consumption relates to prevalence of syphilis among gay and bisexual men using PrEP, it was estimated that 114 doxyPEP courses were taken for every man taking PrEP who is estimated to have syphilis. The researchers did not comment on whether this is an appropriate level of use.

Implications

The authors highlight that although their model suggests doxyPEP could represent a significant proportion of annual doxycycline use in Europe, this should not be interpreted as evidence of doxyPEP contributing to antimicrobial resistance. Many factors influence whether antimicrobial resistance emerges, including the extent and duration of exposure to particular antibiotics. What this study does is provide a benchmark for quantifying doxyPEP use among PrEP users, within wider antibiotic usage in Europe.

The estimates the authors have made show a wide range, which is indicative of the lack of clarity around current doxyPEP use. This uncertainty (between an additional 0.5 million and 18.1 million DDDs) is partly due to difficulty in estimating the population sizes of men who have sex with men across Europe. 

The lower end of this estimate may represent a modest increase compared to total doxycycline consumption. However, as doxyPEP largely represents an increase in antibiotic burden within a relatively small group, this may represent increased selection pressure for antimicrobial resistance. Further analysis combining estimates of doxyPEP usage with evidence from clinical trials could help establish whether projected doxycycline usage is proportionate to the number of syphilis infections it would be expected to prevent.

Reference

Hansson D et al. Estimating the impact of doxycycline post-exposure prophylaxis on antibiotic consumption among men who have sex with men using PrEP in the EU/EEA. Eurosurveillance 3, 2026 (open access).