By: Marcus J. Hopkins, Health Policy Lead Consultant, ADAP Advocacy
Recent studies have shown that DoxyPEP (doxycycline post-exposure prophylaxis) is becoming less effective against the bacterial sexually transmitted infection (STI) gonorrhea. Concerns are rising among certain public health groups, such as the Centers for Disease Control & Prevention and European counterparts, but Doxy-PEP remains regarded as a highly effective prevention method for high-risk groups.
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For the uninitiated, DoxyPEP is a post-exposure oral medication provided within 72 hours after a sexual encounter that reduces the likelihood of acquiring bacterial STIs, including syphilis, chlamydia, and gonorrhea. In the initial DoxyPEP trial, researchers found that the incidence of syphilis decreased by 87%, chlamydia by 88%, and gonorrhea by 55% (Dall, 2026). After this initial study, the Centers for Disease Control and Prevention (CDC) released clinical guidelines for its utilization in 2024 (Bachmann et al., 2024).
Even in the initial study, the reduced incidence of gonorrhea was modest, at best; subsequent studies have shown that a rapid increase in tetracycline-resistant strains of gonorrhea has greatly reduced or all but eliminated DoxyPEP’s efficacy against the infection.
Research published in JAMA Internal Medicine found that the incidence of STI cases of syphilis and chlamydia in San Francisco, CA, decreased significantly among Men who have Sex with Men (MSM) and transgender women against projected case numbers, while the incidence of gonorrhea increased significantly (Sankaran et al., 2025).
Another study published in Clinical Infectious Diseases suggests that widespread utilization of DoxyPEP may actually be contributing to the increase in tetracycline-resistant gonorrhea strains in King County, Washington state, which has resulted in the county health department revising its guidelines on the utilization of doxycycline to treat other bacterial issues, including skin and soft tissue infections and lower respiratory tract infections (Soge et al., 2025).
A third study published in The Lancet Infectious Diseases similarly suggests that widespread utilization of DoxyPEP may be inadvertently increasing the propagation of multidrug-resistant strains of gonorrhea in southern California (Yechezkel et al., 2026).
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Drug-resistant strains of gonorrhea have been a concern in the United States for some time, and researchers have been sounding the call against overreliance upon DoxyPEP as a harm reduction tool against the STI for just as long. A correspondence published in the New England Journal of Medicine in 2025 warned that multidrug-resistant strains have been spreading globally, including strains that carry resistance to the antibiotic ceftriaxone (Helekal et al., 2025).
Sexual health advocates have been heralding DoxyPEP as one of the first effective methods for preventing STIs transmission since the findings of the initial study, including those at the American Sexual Health Association (ASHA, 2025). There is no doubt that DoxyPEP has clearly been shown to be effective against syphilis and chlamydia; however, ADAP Advocacy recommends that organizations begin having realistic conversations about its efficacy against, as well as the continued increase in propagation of, multidrug-resistant strains of gonorrhea.
These conversations need not be “sex-negative,” focusing on fear and shame-based representations of sexual activity; they do, however, need to be realistic.
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Disclaimer: Guest blogs do not necessarily reflect the views of the ADAP Advocacy Association; rather, they provide a neutral platform for the author to promote open, honest discussion of public health-related issues and updates.
References:
[1] American Sexual Health Association. (2025, May 09). Learn More About Doxy PEP from Three People Who Take It. Research Triangle Park, NC: American Sexual Health Association. https://www.ashasexualhealth.org/learn-more-about-doxy-pep-from-three-people-who-take-it/
[2] Bachmann, L. H., Barbee, L. A., Chan, P., Reno, H., Workowski, K. A., Hoover, K., Mermin, J., & Mena, L. (2024, June 06). CDC Clinical Guidelines on the Use of Doxycycline Postexposure Prophylaxis for Bacterial Sexually Transmitted Infection Prevention, United States, 2024. Morbidity and Mortality Weekly Report Recommendations and Reports, 73(2): 1-8. http://dx.doi.org/10.15585/mmwr.rr7302a1
[3] Dall, C. (2026, May 11). Study shows doxyPEP’s diminished effectiveness against gonorrhea. Minneapolis, MN: University of Minnesota: Research and Innovation Office: Center for Infectious Disease Research and Policy: Antimicrobial Stewardship. https://www.cidrap.umn.edu/antimicrobial-stewardship/study-shows-doxypep-s-diminished-effectiveness-against-gonorrhea
[4] Helekal, D., Mortimer, T. D., & Grad, Y. H. (2025, July 09). Expansion of tetM-Carrying Neisseria gonorrhoeae in the United States, 2018–2024. New England Journal of Medicine, 393(2), 198-200. https://doi.org//10.1056/NEJMc2504010
[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, January 06). Doxycycline Postexposure Prophylaxis and Sexually Transmitted Infection Trends. JAMA Internal Medicine, 185(3), 266-272. https://doi.org/10.1001/jamainternmed.2024.7178
[6] Soge, O. O., Thibault, C. S., Cannon, C. A., McLaughlin, S. E., Menza, T. W., Dombrowski, J. C., Fang, F. C., & Golden, M. R. (2025, June). Potential Impact of Doxycycline Post-Exposure Prophylaxis on Tetracycline Resistance in Neisseria gonorrhoeae and Colonization With Tetracycline-Resistant Staphylococcus aureus and Group A Streptococcus. Clinical Infectious Diseases, 80(6), 1,188-1,196. https://doi.org/10.1093/cid/ciaf089
[7] Yechezkel, M., Helekal, D., Kapadia, B., Hong, V., Pomichowski, M. E., Reyes, I. A. C., Davis, G. S., Müller, N. F., Grad, Y. H., Tartof, S. Y., & Lewnard, J. A. (2026, May 07). Durability of doxycycline effectiveness against gonorrhoea after implementation of post-exposure prophylaxis in southern California, USA: a retrospective, test-negative, observational study. The Lancet Infectious Diseases. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(26)00123-4/fulltext
