The early rollout of doxyPEP in San Francisco has contributed to a decline in sexually transmitted infections, according to studies presented March 4 at the Conference on Retroviruses and Opportunistic Infections in Denver. DoxyPEP refers to taking a single dose of the antibiotic doxycycline within 72 hours after sex.
"We are seeing early evidence of the potential for a population-level impact of doxycycline on chlamydia and syphilis rates," said Dr. Stephanie Cohen, director of HIV/STI Prevention for the San Francisco Department of Public Health. "I think this is quite an encouraging result, after over a decade of steadily rising STI rates."
In keeping with its pioneering role in the fight against HIV, San Francisco was the first city to issue local doxyPEP guidelines, and it is the first to see outcomes in clinical practice and at the population level. The new real-world findings back up evidence from clinical trials showing that doxyPEP can substantially reduce chlamydia and syphilis, though it is less effective against gonorrhea.
"This effort is a tremendous example of the rapid translation of research into public health practice and shows that this promising prevention tool has the impact to help turn the curve on the epidemic of STIs that we have been facing in San Francisco and across the nation," gay San Francisco health director Dr. Grant Colfax said a statement.
DoxyPEP in clinical practice
Dr. Annie Luetkemeyer of UCSF reported the latest findings from the DoxyPEP trial, which enrolled more than 500 gay and bisexual men and transgender women in San Francisco and Seattle who were either living with HIV or taking PrEP.
As Luetkemeyer first reported at the 2022 International AIDS Conference, study participants randomly assigned to use doxyPEP saw about an 80% drop in chlamydia and syphilis and a 55% decline in gonorrhea. At CROI, she reported follow-up data showing that risk reduction was sustained among participants initially randomized to doxycycline. Among those initially assigned to standard care and offered doxyPEP after its effectiveness was known, STI incidence fell steeply even though the number of sex partners and condomless sex acts doubled in the short term.
Dr. Hyman Scott reported early results from the San Francisco AIDS Foundation's Magnet clinic at its Strut health center in the LGBTQ Castro neighborhood, where doxyPEP has been offered to around 3,000 active PrEP users starting in November 2022, a month after the San Francisco Department of Public Health issued the first doxyPEP guidelines.
As the Bay Area Reporter previously reported, the Centers for Disease Control and Prevention issued the first national doxyPEP guidance a year later. The CDC recommends doxyPEP for cisgender men who have sex with men and transgender women who have had an STI during the past year. SF's guidance is broader, including trans men and nonbinary people, as well as people with multiple sex partners who haven't recently had an STI.
Gay and bisexual men in San Francisco were early adopters of PrEP for HIV, and the same is true for doxyPEP. Prophylactic doxycycline use at Magnet ramped up steadily, reaching 1,209 people by September 2023. Since then, the number has nearly doubled, according to SFAF. Among people who started doxyPEP, quarterly STI incidence fell by 58% overall. But, as in clinical trials, the decrease was greater for chlamydia (67%) and early syphilis (78%) than for gonorrhea (a nonsignificant 11% drop).
"We've been really impressed by how much our community wanted this, how many people took it when it was available, and what the impact of it was — both quite dramatic and quick," Scott told reporters at a media briefing.
Although most doxyPEP recipients were cisgender men, transgender women and nonbinary people also had high uptake. White, Black, Latino, and Asian PrEP users were about equally likely to opt for doxyPEP, at around 40%. But because Black gay men are far less likely than white or Latino men to be on PrEP, doxyPEP uptake is still not equitable.
"There is still a lot of work to be done around PrEP access" to ensure that disparities are not perpetuated, Scott acknowledged.
Still, SFAF officials noted the positive doxyPEP news.
"For so long, we have only been able to rely on condoms for STI prevention — and we know that condoms don't work for everyone," Jorge Roman, RN, Magnet's senior director of clinical services, said in a statement. "It is exciting to have a new tool that we can make available for STI prevention."
Similarly, SFDPH researcher Dr. Oliver Bacon and colleagues reported early doxyPEP data from City Clinic, comparing STI incidence before and after the local guidelines were issued. Among 506 gay men and trans women on PrEP, 73% started doxyPEP. Positive chlamydia tests dropped by 90% and early syphilis fell by 56% among doxyPEP users compared with 27% and 32%, respectively, among non-users. Gonorrhea declined by about a quarter in both groups, showing that doxyPEP had no significant effect.
STIs at the population level
Other researchers assessed the impact of doxyPEP a different way, looking at changes in STI incidence at the population level.
SFDPH epidemiologist Madeline Sankaran and colleagues tracked the number of people starting doxyPEP and changes in STI rates at Magnet, City Clinic, and Ward 86 at Zuckerberg San Francisco General Hospital and Trauma Center before and after the release of the city guidelines.
More than 3,700 gay and bi men and trans women started doxyPEP at the three clinics by the end of 2023. This is an underestimate of citywide use, as large health systems like Kaiser Permanente and independent practitioners also provide doxyPEP. Chlamydia cases in this population declined by 50% and early syphilis decreased by 51% relative to predicted levels. But again, there was no significant change in gonorrhea.
In a related study, Dr. Jeffrey Klausner of the University of Southern California, and a former San Francisco deputy health officer, and colleagues found that rectal chlamydia, rectal gonorrhea, and syphilis rose among men in San Francisco from April 2020 through December 2021. After that, rectal chlamydia was stable until the city doxyPEP guidelines were issued, after which it declined steeply. Rectal gonorrhea and syphilis were already decreasing before the guidelines and continued to fall.
As these studies suggest, it can be hard to tease out the effects of doxyPEP from pre-existing trends in STI rates and changes due to other factors. For example, COVID disrupted STI screening in early 2020, and many gay men changed their sexual behavior in response to the 2022 mpox outbreak.
But while chlamydia cases among gay men fell after the city's doxyPEP guidelines were issued, cases rose among cisgender women, which "strengthens the conclusion that the decline in chlamydia and early syphilis cases is related to doxyPEP rollout," Sankaran said.
STI prevention for cisgender women remains a glaring gap. Unlike the DoxyPEP trial for gay men and trans women, the dPEP Kenya trial found that doxyPEP did not prevent STIs among young cisgender women in Africa, probably due to low adherence and a high local level of drug-resistant gonorrhea. Neither the San Francisco nor CDC doxyPEP guidelines include a recommendation for cisgender women or heterosexual cisgender men, though it could be considered on a case-by-case basis, according to Cohen.
"Given what we have found to date, I think providers should support their patients in assessing their need for and interest in use of doxyPEP," Cohen said. "DoxyPEP doesn't stand alone. We need everything from primary prevention, including condoms, and education to policy change that supports sexual health."
"For so long, we have only been able to rely on condoms for STI prevention -- and we know that condoms don't work for everyone," Jorge Roman, Magnet's senior director of clinical services said in a statement. "It is exciting to have a new tool that we can make available for STI prevention."
Never miss a story! Keep up to date on the latest news, arts, politics, entertainment, and nightlife. Sign up for the Bay Area Reporter's free weekday email newsletter. You'll receive our newsletters and special offers from our community partners.
Support California's largest LGBTQ newsroom. Your one-time, monthly, or annual contribution advocates for LGBTQ communities. Amplify a trusted voice providing news, information, and cultural coverage to all members of our community, regardless of their ability to pay -- Donate today!