The early rollout of doxyPEP — a dose of the antibiotic doxycycline after sex — has contributed to a decline in sexually transmitted infections in Northern California, according to a pair of studies published this week. While rates of chlamydia and syphilis declined considerably, doxyPEP had less effect on gonorrhea.
"The findings are a huge step forward for sexual health," Dr. Stephanie Cohen, director of STI and HIV prevention and control at the San Francisco Department of Public Health, told the Bay Area Reporter. "While doxyPEP has been shown to be effective in randomized controlled trials, this analysis is the first to demonstrate that doxyPEP can reduce the incidence of sexually transmitted infections at the population level."
DoxyPEP involves taking a single 200-milligram dose of doxycycline within 72 hours after sex. As the B.A.R. previously reported, results from the DoxyPEP trial, first presented at the 2022 International AIDS Conference, showed that the intervention lowered the risk of chlamydia and syphilis for gay men and transgender women, with a smaller but still significant decline in gonorrhea. However, the dPEP Kenya trial found that this approach did not work well for cisgender women in Africa.
In keeping with its pioneering role in the fight against HIV, San Francisco was the first city to recommend doxyPEP. The city's latest guidance goes beyond the Centers for Disease Control and Prevention's national doxyPEP guidelines, offering it for transgender men and nonbinary people as well as cisgender men who have sex with men and trans women.
"We were confident in the potential of doxyPEP, which is why San Francisco led the way in releasing doxyPEP guidance in October 2022," Cohen said, adding that the intervention "is a great example of the rapid translation of research into public health practice."
Real-world evidence
San Francisco DPH epidemiologist Madeline Sankaran and colleagues compared monthly cases of chlamydia, gonorrhea, and early syphilis before (July 2021 through October 2022) and after (November 2022 through November 2023) the city issued its guidance. The results, first reported at the Conference on Retroviruses and Opportunistic Infections last March, have now been published in JAMA Internal Medicine.
More than 3,900 men who have sex with men and transgender women started doxyPEP at three sentinel clinics — City Clinic, Zuckerberg San Francisco General Hospital and Trauma Center's Ward 86, and the San Francisco AIDS Foundation's Magnet clinic at its Strut health center in the Castro — by the end of 2023. This is an underestimate of citywide use, as health systems like Kaiser Permanente and independent practitioners also provide doxyPEP.
Citywide, there were 6,694 cases of chlamydia, 9,603 cases of gonorrhea, and 2,121 cases of early syphilis among gay men and trans women during the study period. Over 13 months, chlamydia cases fell by 50% relative to predicted levels, while early syphilis decreased by 51%. In contrast, there was a small but statistically significant rise in gonorrhea.
The researchers could not rule out other factors that may have affected their findings, for example, changes in STI screening in the wake of COVID or sexual behavior change in response to the 2022 mpox outbreak. Nonetheless, the sharp decrease in cases among gay men after a decade of rising STIs, as well as the fact that there was no corresponding decline in chlamydia among cisgender women (a group not indicated for prophylactic doxycycline) suggest that doxyPEP is having a real effect.
"As a provider of doxyPEP to our community, we are glad to see the impact that this powerful STI prevention strategy is having on reducing the incidence of STIs in San Francisco," Jorge Roman, senior director of clinical services at the AIDS foundation, told the B.A.R. "Data from our own clinic, and from others across the city, show that doxyPEP is making a significant difference, not only for reducing individual risk, but for reducing levels in the community as well."
Kaiser study
In the second study, published in the same journal, researchers at Kaiser Permanente and collaborators in Boston analyzed doxyPEP use and STI rates among people receiving HIV PrEP through Kaiser Permanente Northern California, which covers San Francisco, Oakland, San Jose, Santa Cruz, Sacramento, and surrounding counties.
Between November 2022 and December 2023, a total of 11,551 Kaiser members received PrEP. Within this population, 2,253 — nearly one in five — also used doxyPEP. Most were gay or bisexual men, and nearly half had an STI during the prior year.
Among doxyPEP recipients, quarterly STI rates dropped after they started using prophylactic doxycycline. Chlamydia fell by 79% and syphilis declined by 80%. In contrast to the city's study, there was a 12% decrease in gonorrhea that was less impressive, but still statistically significant. Specifically, declines were significant for rectal and urethral gonorrhea, but not for pharyngeal (throat) gonorrhea. In contrast, no changes in STI rates were seen for people who did not use doxyPEP during the same period.
"Our patients have enthusiastically embraced this proactive approach to reduce their STI risk. After doxyPEP became available for our PrEP patients, we have seen a dramatic decline in positive STI tests and less need for treatment after STI exposures," study coauthor Dr. Jonathan Volk of Kaiser Permanente San Francisco stated in a news release. However, he added, "These modest reductions in gonorrhea rates reinforce the importance of regular STI testing for patients on doxyPEP and the need for novel prevention strategies for gonorrhea prevention, like vaccines that are currently in development."
Taken together, these studies add to the growing body of evidence that doxyPEP is an effective tool for reducing STIs among gay and bi men and trans women. Further study is needed to determine whether a similar approach might be feasible for cisgender women and trans men.
"We are glad to see the conversation about doxyPEP continuing and interest in it rising," Cohen said. "Providers should support their patients in assessing their need for, interest in, and use of doxyPEP, and think about doxyPEP as part of a comprehensive package of sexual health services that includes education, HIV pre-exposure prophylaxis, vaccines, and STI screening."
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