Steep Decline in Chlamydia, Syphilis Rates 'Seals the Case' for DoxyPEP

— Other data showed high uptake of doxycycline post-exposure prophylaxis among PrEP users


DENVER -- Chlamydia and early syphilis cases among at-risk individuals were halved after the introduction of doxycycline post-exposure prophylaxis (doxyPEP), real-world data from San Francisco showed.

Over a 13-month period following the rollout of doxyPEP to high-risk men who have sex with men (MSM) and transgender women, monthly chlamydia cases decreased by 50% (95% CI 38-59) while syphilis cases decreased by 51% (95% CI 43-58) compared with projected numbers, according to Madeline Sankaran, MPH, of the San Francisco Department of Public Health, who presented the findings at the Conference on Retroviruses and Opportunistic Infections (CROI).

No difference, however, was observed for gonorrhea cases after the city's rollout of doxyPEP in 2022, when the cheap antibiotic was either recommended for MSM and transgender women with a bacterial sexually transmitted infection (STI) and history of condomless sex during the past year, or offered to this patient population if they'd had multiple sex partners over the prior year.

Another study presented during the same session at CROI reported high uptake of doxyPEP among people at a San Francisco clinic already taking HIV pre-exposure prophylaxis (PrEP), while yet a third study demonstrated sustained decreases in STI rates for randomized trial participants who used the antibiotic after condomless sex.

"DoxyPEP has really changed the face of STI prevention and control," commented Landon Myer, MD, of the University of Cape Town in South Africa, who moderated a press briefing highlighting the studies.

"It's not often that you have population health, in concordance with clinical service delivery cohorts, in concordance with clinical trial results, all at the same time," said Myer, who was not involved with the research. Together, the findings, "to my mind, seals the case. This is really unusual from a public health perspective for an intervention that is so new."

DoxyPEP Associated With Citywide Decrease in STIs

Following trial data showing the benefit of doxyPEP for reducing bacterial STI incidence, the San Francisco Department of Public Health in October 2022 became the to recommend doxyPEP for at-risk populations. The department issued guidelines and began distributing doxycycline, a tetracycline antibiotic, to MSM and transgender women through high-volume clinics to reduce the risks for syphilis, gonorrhea, and chlamydia.

These at-risk groups are disproportionately affected by San Francisco's high and growing burden of STIs, said Sankaran. From 2014 to 2019, for example, citywide surveillance data showed a 76% increase in chlamydia cases among these individuals, along with a 45% rise in early cases of syphilis and a 72% rise in gonorrhea.

To assess the impact of the doxyPEP intervention, the researchers estimated the number of predicted cases of chlamydia (~250 per month) and early syphilis (~90 per month) using an autoregressive integrated moving average model.

Following doxyPEP's introduction, reported STI cases from November 2022 to November 2023 in the city's MSM and transgender women population decreased by 6.6% monthly for chlamydia and by 2.7% for early syphilis when compared with the projections (P<0.0001 for both), said Sankaran.

The findings were further supported by increases in chlamydia among cisgender women during the study period.

"This is the first analysis to show that doxyPEP has the potential to have a population-level impact on STIs," Sankaran said at the press conference. "We're very encouraged by the findings, and we'll be following citywide STI trends closely to see if these positive trends continue."

Factors such as changes in screening and sexual practices -- for example, in response to the mpox outbreak -- may have contributed to the observed trends, Sankaran acknowledged.

DoxyPEP Uptake High Among PrEP Users

Following the health department's recommendation, a large sexual health clinic in the Castro neighborhood of San Francisco experienced a high uptake of doxyPEP among patients taking PrEP for HIV prevention, as well as an overall decline in STI incidence, reported Hyman Scott, MD, MPH, also of the San Francisco Department of Public Health.

Among 3,081 active PrEP users, 39% decided to take doxyPEP over the 9 months after being introduced at the clinic in December 2022.

"Over time, more and more of our clients decided to take doxyPEP," said Scott, noting that the rollout was facilitated by client-centered advertising, social media posts, and discussion at routine PrEP visits.

"We saw very high uptake of doxyPEP among our client population, reflecting a very strong demand among potential users," said Scott. "People wanted this and [were] waiting to be able to get it."

Uptake was largely consistent across race/ethnicity and age groups, though lower rates were observed among people ages 60 and up (27%) compared with younger adults (34% to 43%). The researchers also found uptake consistency across gender identities with the exception of the 14 cisgender women and the 32 transgender men (0% and 25% uptake, respectively).

The researchers also evaluated STI incidence at the clinic before and after offering doxyPEP. Among doxyPEP users, STIs declined from an absolute 18% during the first quarter of the study (June-August 2022, before the antibiotic was offered) to 7.5% in the last quarter of the study (June-August 2023).

Incidence among the doxyPEP users declined by a relative 58% for all STIs (incidence rate ratio [IRR] 0.42, 95% CI 0.24-0.74), by 78% for syphilis (IRR 0.22, 95% CI 0.09-0.54), and by 67% for chlamydia (IRR 0.33, 95% CI 0.23-0.46). No significant decline was observed with gonorrhea, possibly due to resistance to tetracycline, Scott said.

Among non-users of doxyPEP, the absolute incidence of all STIs showed a small decline during the study, from 7.5% in June-August 2022 to 6.5% in June-August 2023.

Open-Label Extension of DoxyPEP Trial Shows Sustained Benefit

New data from the open-label extension of the randomized DoxyPEP trial showed that doxyPEP was associated with a sustained decrease in the incidence of STIs in MSM and transgender women, despite an increase in participants' sexual partners and condomless sex acts, Annie Luetkemeyer, MD, of the University of California San Francisco, reported at CROI.

Among participants initially assigned to standard care, the incidence of STIs per quarter decreased from 31% during the randomized part of the trial to 17% during the open-label extension when these participants started taking doxyPEP following condomless sex.

STI incidence per quarter was stable among participants initially assigned to doxyPEP who remained on doxyPEP during the open-label part of the trial as well (11% to 13%), Luetkemeyer told attendees.

Reported doxyPEP coverage per condomless sex act was high in both groups, at greater than 75%.

"The STI epidemic continues both in the U.S. and globally and has really impacted particularly men who have sex with men and trans women with really shocking increases in syphilis, but also sustained rises in chlamydia and gonorrhea," she told attendees.

The primary efficacy cohort for included 592 patients randomized 2:1 to either doxyPEP (doxycycline 200 mg within 72 hours of condomless sexual contact, one dose per day maximum) or standard care. The trial showed a 65% reduction in bacterial STIs each quarter of the study, with an 80% reduction in chlamydia and syphilis and a 50% reduction in gonorrhea.

Because doxyPEP was so effective, the study was terminated early and people randomized to the control group were offered doxyPEP. The open-label extension trial enrolled 289 participants, including 207 from the initial doxyPEP cohort and 82 control participants who chose to start doxyPEP.

Of note, Luetkemeyer reported that sexual partnerships and condomless sex acts increased in both groups during the open-label part of the trial, but especially among the standard-care group who switched to doxyPEP. The number of sex partners, condomless insertive sex, and receptive sex acts doubled in this group.

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    Katherine Kahn is a staff writer at app, covering the infectious diseases beat. She has been a medical writer for over 15 years.


Sankaran had no disclosures.

Scott reported grants from Gilead Sciences and ViiV Healthcare.

Luetkemeyer's study was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and medicines and laboratory support were provided by Hologic, Cepheid, and Mayne Pharma. Luetkemeyer reported consulting fees from Vir Biotechnology and institutional grants from Gilead, Merck Sharp & Dohme, and ViiV.

Myer had no disclosures.

Primary Source

Conference on Retroviruses and Opportunistic Infections

Sankaran M "Doxy-PEP associated with declines in chlamydia and syphilis in MSM and trans women in San Francisco" CROI 2024; Abstract 127.

Secondary Source

Conference on Retroviruses and Opportunistic Infections

Scott H "Doxycycline PEP: high uptake and significant decline in STIs after clinical implementation" CROI 2024; Abstract 126.

Additional Source

Conference on Retroviruses and Opportunistic Infections

Luetkemeyer A "sustained reduction of bacterial STIs during the DoxyPEP study open-label extension" CROI 2024; Abstract 125.