Real-World Data Yields Promise for DoxyPEP

By: Ranier Simons, ADAP Blog Guest Contributor

Sexually transmitted diseases (STIs) are serious, highly communicable diseases that, left unchecked, can cause serious harm and even be life-threatening. Some, such as HIV, are incurable. Others can be disfiguring, cause sterility, or even brain damage and congenital abnormalities. (NIH, 2017). Three of the most common curable STIs are syphilis, chlamydia, and gonorrhea. In the U.S., over 2.4 million cases of syphilis, gonorrhea, and chlamydia combined were diagnosed and reported in 2023. (Press, 2024). A recent treatment innovation being adopted in the fight against STIs is doxycycline post-exposure prophylaxis, commonly referred to as doxyPEP. Clinical trials have shown promising results, and recent data shows the promise of its effectiveness in real-world populations of sexual networks.

Photo Source: Chicago Department of Public Health

DoxyPEP is the administration of 200 mg of doxycycline within 24 hours of unprotected sex. (Lou, 2025). Two previous clinical trials, the DOXY/PEP study in the U.S. and the DOXYVAC study out of France, indicate that DoxyPEP is effective for STI prevention. However, the sample sizes of the studies were small, and it is necessary to investigate the effectiveness of the intervention on larger populations out in the real world. The DOXY/PEP study contained 501 participants, and the DOXYVAC study included 556. (Molina, 2024; Susman, 2022). Two recent studies indicate the high efficacy of more extensive population-level doxyPEP implementation. One study was conducted in San Francisco, and the other studied populations in Northern California.

The study out of San Francisco was a population-level interrupted time series analysis of STI cases of men who have sex with men (MSM) and transgender women before and after the city issued citywide doxyPEP guidelines in 2022. (Sankaran, 2025) During the study period, there were 6694 cases of chlamydia, 9603 cases of gonorrhea, and 2121 cases of early syphilis. The study's objective was to observe the percentage differences between STI-modeled projected infections and observed STI rates after citywide doxyPEP was initiated. By the end of the study period, chlamydia cases had decreased -49.64% and early syphilis cases by -51.39% compared to projected case levels. However, there was an increase in gonorrhea cases compared with projections.

The Northern California study was a retrospective cohort examination of adult Kaiser Permanente Northern California (KPNC) members who were given HIV PrEP from November 1, 2022, through December 31, 2023. (Trager, 2025) In the study of 11,551 subjects, 2253 were dispensed doxyPEP. The primary outcome of the study was the examination of quarterly rates of STI positivity. Among those on doxyPEP, quarterly chlamydia positivity decreased from 9.6% before doxyPEP administration to 2.0% after. Gonorrhea positivity decreased from 10.2% to 9.0%. Syphilis positivity lowered from 1.7% to 0.3%. Rates remained stable among those who were not utilizing doxyPEP.

The CDC has officially recommended the use of doxyPEP for STI prevention for MSM and transgender women since June of 2024. (Lou, 2025). Counseling for doxyPEP is especially encouraged for members of this population who have had at least one STI infection in the past year. Notably, doxyPEP has had questionable efficacy related to gonorrhea. In the San Franciso study, there was an increase in gonorrhea cases. The Kaiser Permanente study showed lower rates of gonorrhea positivity in rectal and urethral site infections with an increase in pharyngeal gonorrhea rates. These findings support the hypothesis that pharyngeal tissues could be a reservoir of gonorrheal antibacterial resistance and the possibility of increased risk of gonorrheal antibacterial resistance overall.

These aforementioned studies indicate that doxyPEP is potentially an efficacious modality of STI prevention not just in clinical studies but also out in the real world. However, larger, more targeted studies must be conducted on wide populations to gain a deeper understanding. The San Francisco and Kaiser Permanente studies only show a correlation and not a causal relationship between doxyPEP and lowered STI rates because the studies are observational. Regardless, doxyPEP is making a significant dent in STI transmissions and only time will reveal its true efficacy and possibility of antibiotic resistance risk.

Photo Source: San Francisco City Clinic

[1] NIH. (2017). Why are sexually transmitted diseases (STDs) and sexually transmitted infections (STIs) of particular concern for pregnant women? Retrieved from  https://www.nichd.nih.gov/health/topics/stds/conditioninfo/concern#:~:text=STIs%20during%20pregnancy%20can%20also%20cause:&text=Miscarriage%20(fetal%20loss%20before%2020,Health%20complications%20in%20the%20mother

[2] Lou, N. (2025, January 6). DoxyPEP Rollout Tied to Dent in STI Epidemic in the Real World. Medpagetoday.com; MedpageToday. Retrieved from https://www.medpagetoday.com/infectiousdisease/stds/113668

[3] Molina, J.-M. (2024). 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. Infectious Diseases/˜the œLancet. Infectious Diseases. https://doi.org/10.1016/s1473-3099(24)00236-6

[4] Press, A. (2024, November 13). STI Epidemic Slows as New Syphilis and Gonorrhea Cases Fall in the U.S. Medpagetoday.com; MedpageToday. Retrieved from https://www.medpagetoday.com/infectiousdisease/stds/112879

[5] Sankaran, M., Glidden, D. V., Kohn, R. P., Nguyen, T. Q., Bacon, O., Buchbinder, S. P., Gandhi, M., Havlir, D. V., Liebi, C., Luetkemeyer, A. F., Nguyen, J. Q., Roman, J., Scott, H., Torres, T. S., & Cohen, S. E. (2025). Doxycycline Postexposure Prophylaxis and Sexually Transmitted Infection Trends. JAMA Internal Medicine. Retrieved from  https://doi.org/10.1001/jamainternmed.2024.7178

[6] Susman, E. (2022, July 29). Post-Exposure Doxycycline Reduces STIs. Medpagetoday.com; MedpageToday. https://www.medpagetoday.com/meetingcoverage/iac/99983

[7] Traeger, M. W., Leyden, W. A., Volk, J. E., Silverberg, M. J., Horberg, M. A., Davis, T. L., Mayer, K. H., Krakower, D. S., Young, J. G., Jenness, S. M., & Marcus, J. L. (2025). Doxycycline Postexposure Prophylaxis and Bacterial Sexually Transmitted Infections Among Individuals Using HIV Preexposure Prophylaxis. JAMA Internal Medicine. Retrieved from https://doi.org/10.1001/jamainternmed.2024.7186

Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association, but rather they provide a neutral platform whereby the author serves to promote open, honest discussion about public health-related issues and updates.