DoxyPEP Rollout Tied to Dent in STI Epidemic in the Real World

A decrease in California’s sexually transmitted infections (STIs) followed early real-world adoption of doxycycline post-exposure prophylaxis (doxyPEP), suggesting real population-level benefits to this public health strategy.

Marking a first for an American health jurisdiction, San Francisco health officials had put doxyPEP into practice in October 2022 with a citywide guideline endorsing doxycycline 200 mg within 72 hours after condomless sex for men who have sex with men (MSM) and transgender women with a history of an STI or multiple sex partners in the past year.

In San Francisco, cases of chlamydia and early syphilis fell steadily and were roughly halved at the 13-month mark after implementation of doxyPEP in the city, one report showed, while at Kaiser Permanente Northern California, incident chlamydia and certain types of site-specific gonorrhea were significantly reduced among doxyPEP user- versus nonuser-members.

Both studies in JAMA Internal Medicine supported the rising profile of doxyPEP as a way to counter the epidemic of syphilis, gonorrhea, and chlamydia infections, even if the data on gonorrhea were relatively less promising.

The San Francisco report, based on citywide public health surveillance data on MSM and transgender women, found steady drops in chlamydia (-6.58% per month) and early syphilis (-2.68%) but a modest increase in incident gonorrhea compared with projections (+1.77% per month), reported Stephanie Cohen, MD, of the San Francisco Department of Public Health, and colleagues. These study results had been previously reported at the 2024 Conference on Retroviruses and Opportunistic Infections.

According to Michael Traeger, PhD, MSc, of Harvard Pilgrim Health Care Institute in Boston, and colleagues, the Kaiser Permanente study showed that among HIV preexposure prophylaxis (PrEP) patients also initiating doxyPEP at Kaiser Permanente, quarterly chlamydia positivity rates fell about 80% in the first year of availability. The decline in quarterly gonorrhea positivity was borderline significantly improved, around 12%, with no reduction in pharyngeal gonorrhea.

In both studies, there was a 19.5% initiation rate of doxyPEP.

Previously, two randomized trials, the DOXY/PEP study in Seattle/San Francisco and the DOXYVAC study in France, established the efficacy of doxyPEP for preventing some bacterial STIs in MSM.

Meanwhile, the latest data show signs the STI epidemic might be slowing, but case counts are still 90% higher than 2004 levels, according to a CDC estimate.

Although doxyPEP is not expected to be a panacea for STIs on a population level, it at least marks some potential progress while other work in STI prevention and treatment is stalled. The CDC has, since June 2024, officially recommended counseling on the use of doxyPEP for STI prevention for MSM and transgender women.

“Although investment in better diagnostic testing is gaining momentum, the pace of vaccine development has been slow, and that of new antibiotic development, given the pharmacoeconomics of STI treatment, for which single-dose therapy has been preferred, has been glacial,” lamented Jeanne Marrazzo, MD, MPH, of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and Jodie Dionne, MD, MPH, of the University of Alabama at Birmingham.

“Research to identify and test new and improved STI therapeutic and prevention options, especially vaccines and antimicrobials, with safety and efficacy in all populations remains paramount,” Marrazzo and Dionne stressed in an accompanying editorial.

Also pressing are concerns about the spread of drug-resistant gonorrhea, which were highlighted by the Kaiser Permanente study.

Traeger’s team found that the little, if any, effectiveness of doxyPEP for pharyngeal gonorrhea is “a pattern that may reflect poor concentration of doxycycline in pharyngeal mucosa and may pose an increased risk of resistance acquisition through horizontal transfer of resistance genes from commensal Neisseria species.”

The finding thus “illuminated a potentially important biological reservoir that could inform the ongoing debate as to whether doxyPEP will exacerbate the relentless evolution of antimicrobial resistance in N. gonorrhoeae,” Marrazzo and Dionne noted, adding that it “raises concern about antimicrobial resistance, data for which in the context of doxyPEP use are only beginning to emerge.”

Authors of both San Francisco and Kaiser Permanente studies acknowledged that they were unable to prove a causal relationship between doxyPEP implementation and reduced STIs due to their observational designs.

And given the target population for doxyPEP, cisgender women remain understudied.

The San Francisco report considered only MSM and transgender women in its analysis of STI rates before (July 2021-October 2022) and after (November 2022-November 2023) the doxyPEP guideline. Three sentinel clinics were used to monitor doxyPEP uptake.

The Kaiser Permanente study included an insured pool of 11,551 adults (mean age 39.9, 95.1% men) who had been dispensed HIV PrEP from November 2022 to December 2023. Pharmacy records gave the authors an estimate of doxyPEP uptake.