Doxycycline for STI prevention shows significantly decreased rates of chlamydia and syphilis in a major clinic

Certain sexually transmitted infections (STIs) are relatively common, such as chlamydia, gonorrhea and syphilis. Doctors, nurses, pharmacists and public health authorities are trying to find ways to decrease the spread of these infections. One method of reducing the risk of these STIs is the use of the antibiotic doxycycline before or after potential sexual exposure. In this CATIE News article, we focus on the use of doxycycline taken after sexual exposure; this use of doxycycline is called doxyPEP.

In a clinical trial several years ago in the U.S. called Doxy-PEP, researchers provided the antibiotic doxycycline 200 mg or a placebo to be taken within 72 hours after condomless sex. This study included people with HIV and without HIV. Researchers found that taking doxycycline reduced the risk for syphilis, chlamydia and gonorrhea by about two-thirds, regardless of HIV status.

Implementing doxyPEP in one large clinic

Since that pivotal study, a team of researchers in San Francisco analyzed data on the risk of STIs from one of the city’s large sexual health clinics (called Magnet). Participants in the analysis were all taking HIV pre-exposure prophylaxis (PrEP) and were offered doxyPEP to be used as outlined previously. People who were not prescribed doxyPEP were used as a control, or comparison, group.

Researchers collected health-related information from 4,592 people between 2022 and 2024. Their average profile was as follows:

• 33 years old
• cisgender men – 89%; nonbinary people – 6%; transgender women – 3%; transgender men – 1%; cisgender women – 1%
• major ethno-racial groups: White – 34%; Hispanic – 24%, Asian – 17%, Black – 4%

During the study, more than half of participants (2,524) initiated doxyPEP. Participants were monitored for about 96 weeks.

Results

According to the researchers, they found “sustained declines in chlamydia and syphilis over 96 weeks after doxyPEP was implemented.” The researchers noted that people who initiated doxyPEP tended to have a history of STIs. This indicated that doxyPEP was being offered to a population that was at high risk for such infections.

Researchers found that participants who initiated doxyPEP disclosed a greater number of condomless sex acts with partners compared to people who were not using doxyPEP. Despite this greater risk behaviour among people prescribed doxyPEP, rates of diagnoses of chlamydia and syphilis were similar among doxyPEP users and people who were not using the antibiotic. This suggests that doxyPEP is highly effective at reducing the risk of chlamydia and syphilis.

Focus on gonorrhea

The researchers noted that “although the rate of gonorrhea [diagnoses] did decrease initially after starting doxyPEP, gonorrhea rates began to increase again towards the end of the analysis.”

The researchers advanced two ideas to explain this finding, as follows:

• It is possible that during the study gonorrhea increasingly developed the ability to resist doxycycline.
• Strains of gonorrhea that are partially or wholly resistant to doxycycline now account for the gonorrhea that doxycycline users are encountering in the city.

Bear in mind

This study is a good first step in confirming the effectiveness of doxyPEP against STIs, particularly chlamydia and syphilis, when implemented at a large sexual health clinic in San Francisco.

However, funding is needed to assess at least the following issues in the future:

• monitoring rates of gonorrhea and other leading STIs
• analyzing gonorrhea for resistance to doxycycline and the response of doxycycline-resistant gonorrhea to recommended treatment (such as the antibiotic ceftriaxone)
• interviewing people who use doxyPEP, to get detailed information on their sexual behaviours and their adherence to instructions for the use of doxyPEP (i.e., how soon after sexual exposure people take it and how frequently it is used). Such research is important because interviews with some of the people who took part in the original doxyPEP study (mentioned at the beginning of this article) found that some people reported confusion about the timing of the dose, particularly when there were multiple sexual partners within a short period of time. What’s more, despite being told to take doxyPEP after condomless sex, including oral sex, the researchers found that several interviewees “were under the impression that they did not need doxyPEP for oral sex.” In part, this confusion arose because some participants perceived oral sex as safer than intercourse.

A different study in another country

In the San Francisco study, doxycycline was provided by an STI clinic.

In the Netherlands, the use of doxycycline to prevent STIs is not recommended. However, researchers in that country recently reported informal use of doxycycline to prevent STIs among a group of mostly gay, bisexual and other men who have sex with men (gbMSM). Although people in the Dutch study disclosed that they wanted to reduce their risk of STIs, exactly how doxycycline was being used was not clear.

The study from the Netherlands underscores the need for additional research into how doxycycline is being used outside of clinical trials.

Also needed are efforts to continue community education as well as research on trends in gonorrhea resistance to antibiotics.

Resources

Doxycycline to help prevent bacterial STIs – CATIE

Understanding the impact of the antibiotic doxycycline on the sexual well-being of users – CATIE News

Exploring the impact of doxycycline to prevent sexually transmitted infections – CATIE News

By Sean R. Hosein

REFERENCES:

1. Spinelli MA, Heise MJ, Roman J, et al. Sustained effectiveness of doxycycline post-exposure-prophylaxis in a large sexual health clinic over 96 weeks: an interrupted time series analysis. Clinical Infectious Diseases. 2025; in press.
2. Teker B, Hoornenborg E, Schim van der Loeff MF, et al. Emergent informal use of doxycycline post- and pre-exposure prophylaxis among men who have sex with men and transgender and gender diverse people, the Netherlands, 2024. EuroSurveillance. 2025 Jul;30(26):2400707.
3. Reichert E, Grad YH. Effects of doxycycline post-exposure prophylaxis for prevention of sexually transmitted infections on gonorrhoea prevalence and antimicrobial resistance among men who have sex with men in the USA: a modelling study. Lancet Microbe. 2024 Nov;5(11):100926.
4. Lefebvre B, Martin I, Thorington R, et al. Extensively drug-resistant Neisseria gonorrhoeae strain, Canada. Emerging Infectious Diseases. 2025 Jul;31(7):1446-1449.