Cases of syphilis, chlamydia, and gonorrhea in San Francisco dropped significantly last year, according to new data from the San Francisco Department of Public Health (SFDPH). The data is good news and comes on the heels of a spike in sexually transmitted infections (STIs) - not just in the Bay Area but across the nation, following the COVID-19 pandemic.
To come to grips with the spike, San Francisco became the first city in the nation, in 2022, to issue public health guidance to administer the common antibiotic doxycycline as a form of post-exposure prophylaxis to prevent STIs for certain high-risk groups, following research by scientists at UC San Francisco, Zuckerberg San Francisco General Hospital, and medical centers in Seattle, in partnership with SFDPH.
Annie Luetkemeyer, MD, professor of infectious diseases at UCSF and Zuckerberg San Francisco General Hospital, led the research team studying the effectiveness of Doxy-PEP if taken less than 72 hours after unprotected sex . Luetkemeyer explains the success of doxy-PEP, the drawbacks, and new therapies on the horizon.
What is doxy-PEP and how does it work?
Post-exposure prophylaxis, or PEP, is a strategy of taking a medication after an exposure to a possible infection following the risk of exposure. The idea of PEP isn't new. We use post-exposure approaches for other infections, such as giving antibiotics after a tick bite in areas where Lyme disease is common or HIV antivirals after sexual or bloodborne exposures.
In this case, doxy-PEP is a single 200 milligram dose of the antibiotic doxycycline taken after condomless sex as soon as possible, but within 72 hours. Right now, it's recommended primarily for men who have sex with men and transgender women because that's where we have the strongest data.
Why was San Francisco so successful in reducing syphilis, chlamydia, and gonorrhea last year?
The recent SFDPH data is really encouraging. In 2025, San Francisco saw about a 24% decrease in syphilis, an 18% decrease in chlamydia, and a smaller, around 5%, decrease in gonorrhea compared to 2024.
Encouragingly, STI rates have been coming down for a few years now. That said, it's important to recognize that we're still above where we were a decade ago, but we're moving in the right direction.
I do think doxy-PEP is likely contributing to some of these declines.
Where have you seen the most success?
What's particularly telling is that the biggest decreases in the San Francisco data are among men who have sex with men and transgender women, which are the groups for whom doxy-PEP recommended and more commonly used.
How effective is doxy-PEP?
In our 2022 study, we saw a really substantial effect of doxy-PEP to reduce new bacterial STIs. There was about an 80% reduction in new chlamydia and syphilis every three months that doxy-PEP was taken compared to no doxy-PEP, and about a 50% reduction in gonorrhea.
We have seen similar results in a similar study from France called DoxyVAC. It's always reassuring when you have multiple large, randomized trials showing concordant results.
Why is doxy-PEP less effective against gonorrhea?
This likely comes down to antibiotic resistance. Doxycycline is in the tetracycline class, and gonorrhea has become increasingly resistant to that class over time.
Gonorrhea is particularly good at developing resistance, and we were already seeing that trend before doxy-PEP was widely used. So, while doxy-PEP may still have some impact on gonorrhea, it's not as reliable for gonorrhea as it is for chlamydia and syphilis and may offer no protection in some populations.
I usually counsel patients not to expect protection from gonorrhea when taking doxy-PEP.
What role did UCSF play in developing doxy-PEP?
We conducted the doxy-PEP trial, one of the key randomized controlled trials that established the effectiveness of doxy-PEP, working with co-investigators in Seattle. Our study was conducted by UCSF and SFDPH investigators at Zuckerberg San Francisco General and the San Francisco municipal STI clinic (City Clinic), as well as at two sites in Seattle.
What we wanted to understand was whether the use of doxy-PEP after condomless sex would reduce the incidence of STIs in men who have sex with men with a history of recent STI.
And the answer was, yes, quite dramatically. Those findings, along with similar studies in France, helped inform CDC guidelines and broader adoption.
Why was San Francisco so successful in effectively implementing doxy-PEP?
When the initial data for doxy-PEP effectiveness came out in 2022, the San Francisco Department of Public Health moved quickly to issue guidance about who should consider doxy-PEP. Their quick action enabled providers, programs, and individuals to make informed decisions based on the available data.
There was also a lot of community engagement so people understood what doxy-PEP is and who may benefit, and, just as importantly, what it isn't.
Can other cities replicate this approach?
I think they can, but it should be a tailored approached, based on local epidemiology and understanding about which communities may benefit from doxy-PEP , in the context of a broader sexual health toolkit.
Doxy-PEP isn't for everyone. It's really meant for people at higher risk of recurrent STIs. From there, it's about partnering with public health departments, providers, and communities to make sure there's clear message about who may benefit and to enable access to doxy-PEP in these populations. That was a big part of what worked in San Francisco.
Are there risks or side effects?
Doxycycline is a medication we've used for a long time, so we understand its potential side effects well. It can cause sun sensitivity, skin rash, and should be taken with a full glass of water to avoid irritation of the esophagus.
The bigger concern is antibiotic resistance. We haven't seen resistance emerge in chlamydia or syphilis, which is reassuring, but we are seeing it in gonorrhea.
We're also studying the broader impact of taking doxycycline intermittently as doxy-PEP on other bacteria in the body, like those in the gut and on the skin.
Does doxy-PEP prevent all STIs?
No. It only works against bacterial STIs like chlamydia, syphilis, and to some extent, gonorrhea.
It does not prevent viral infections like HIV, human papillomavirus (HPV), herpes, or mpox. That said, we have vaccines for HPV and mpox and we have excellent preventive medicines for HIV (HIV-PrEP). We don't have good preventive medication or vaccines for herpes, but we do have good treatments for those who develop the disease.
Are there new prevention options on the horizon?
At the moment, there aren't new pre-exposure or post-exposure prevention tools like doxy-PEP that are ready for bacterial STIs. There's a lot of interest in vaccines - especially for gonorrhea - but initial data for use of the meningococcal vaccine to prevent gonorrhea in men have been disappointing.
What about new treatments?
Two new antibiotics, gepotidacin and zoliflodacin, have been approved by the FDA for the treatment of gonorrhea. What's exciting is that they are in two new classes of antibiotics, which is important because gonorrhea has developed resistance to many existing antibiotics.
There are also studies underway on the efficacy of doxy-PEP on women.
Are there any concerns despite the progress so far?
Yes. While it's great to see overall declines in STI in the SF DPH 2025 data, these declines are not happening equally across all groups. The reductions in syphilis have been smaller in women, and we're still seeing cases of congenital syphilis, which is a tragedy. There are also persistent racial and ethnic disparities in STI incidence.
So, I think the key question moving forward is: who are we not reaching, and how can we reduce the risk for STIs for everyone at risk?
