As health care services begin offering doxycycline to prevent bacterial sexually transmitted infections (STIs), real-world evidence demonstrates that the postexposure strategy, called doxy PEP, is reducing the rate of syphilis and chlamydia, but has had little to no effect on gonorrhea and needs close monitoring for signals of antibiotic resistance. Today, JAMA Internal Medicine published two reports of early results of doxy PEP rollout in California. Encouraging signals and remaining scientific questions from those reports are highlighted in an accompanying commentary by Jeanne Marrazzo, M.D., M.P.H., director of the National Institutes of Health's National Institute of Allergy and Infectious Diseases (NIAID), and Jodie Dionne, M.D., M.P.H., associate professor of medicine in the Division of Infectious Diseases and associate professor of obstetrics and gynecology in the Division of Maternal-Fetal Medicine at the University of Alabama at Birmingham.
"These reports are part of the crucial scientific process of translating clinical research to implementation at scale," said Dr. Marrazzo. "Doxy PEP is proving to be an important intervention in our effort to decrease STI incidence while we continue to invest in research to develop safe and effective preventive vaccines and next-generation antibiotics."
The Centers for Disease Control and Prevention (CDC) reported more than 2.4 million cases of syphilis, gonorrhea, and chlamydia in the United States in 2023, including 3,882 cases of congenital syphilis, of which 279 resulted in stillbirths and infant deaths. While the latest data show signs the STI epidemic might be slowing, case counts are still 90% higher than 2004 levels and present a threat to peoples' health.
Taking oral doxycycline within 72 hours of condomless sex reduced the incidence of the bacterial STIs syphilis, chlamydia and gonorrhea by two-thirds among gay, bisexual, and other men who have sex with men and transgender women in a recent randomized controlled trial. However, the antibiotic had no preventive effect in a similar study in cisgender women. Based on this evidence, the CDC recommends that U.S. health care providers discuss doxy PEP with men who have sex with men and transgender women who have a history of at least one bacterial STI.
In one of the new published analyses, public health surveillance data from selected public clinics in San Francisco showed that cases of early syphilis and chlamydia in men who have sex with men and transgender women decreased by 50% and 51%, respectively, after 13 months of targeted doxy PEP implementation, but gonorrhea incidence increased by 26% in the same time period. In the other analysis, pharmacy prescription data from an integrated health system in California showed that after 12 months of doxy PEP rollout in people assigned male sex at birth who were also taking HIV pre-exposure prophylaxis, STI positivity rates declined by 79%, 80%, and 12% for chlamydia, syphilis, and gonorrhea, respectively. The declines in gonorrhea were limited to infections at the urethra and rectum. No declines were seen at the pharynx—throat—a common site where people acquire gonorrhea.
In their commentary , Drs. Marrazzo and Dionne celebrated doxy PEP's substantial effect on chlamydia and syphilis in routine health service settings. They cautioned that the mixed results on gonorrhea, along with results from another recent study showing people taking doxy PEP had some evidence of resistance to a class of antibiotics for gonorrhea treatment, point to the need to closely track the development of antimicrobial resistance in the context of doxy PEP use and to include measures of drug resistance in all doxy PEP studies. They also noted some disparities in doxy PEP uptake and the need to ensure equitable knowledge, acceptability, and access as rollout continues.
Reflecting on ongoing research needs, Drs. Marrazzo and Dionne pointed to the persistent gaps in doxy PEP evidence for cisgender women. They called for research to better understand the relationship between doxycycline dosing frequency and its preventive efficacy in real-world settings, as well as the durability of doxy PEP's protective effects. Finally, they highlight broader STI intervention needs, including safe and effective vaccines and new antibiotics for all people affected by STIs.
Reference: JM Marrazzo and JA Dionne. DoxyPEP to Prevent Bacterial STIs—Ready for Prime Time? JAMA Internal Medicine DOI: 10.1001/jamainternmed.2024.7165 (2025).
NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website .
