California's ‘Plan B for STIs' is working - with one exception

A drug meant to prevent sexually transmitted infections if taken within 72 hours of unprotected sex appears to be working well against syphilis and chlamydia, but within a year of making the therapy widely available in California, it no longer protects against gonorrhea, according to a new Kaiser study.

DoxyPEP, a dose of antibiotics sometimes framed as Plan B for STIs, cut the risk of getting syphilis or chlamydia by up to 60%, according to the Kaiser study, which looked at roughly 25,000 members in Southern California. But it had no effect against gonorrhea, and there are signs that doxyPEP may be contributing to drug resistance in the bacteria.

The overall results are promising for a new class of therapy that is seen as a potentially important tool against rising rates of sexually transmitted infections, public health experts said. The study results around gonorrhea were disappointing but not surprising, they said. Drug resistance in gonorrhea has been an increasing problem for decades, and though doxyPEP may have sped up the process, that doesn't mean people should stop using it. In fact, San Francisco this month updated its guidelines for use and now recommends it for some high-risk cisgender women.

"Two of the three target infections are still being prevented at about 60% two years after rollout, and those benefits look durable," said Dr. Jake Scott, an infectious disease expert with Stanford who was not involved with the Kaiser study.

Rates of sexually transmitted infections have been climbing across the United States for two decades; they're particularly troubling with regard to syphilis, which can cause terrible outcomes when women are infected during pregnancy. Rates of congenital syphilis have nearly doubled in the United States over the past five years.

"The situation (with syphilis) is genuinely alarming," Scott said. "These are babies who can be stillborn or born with bone deformities or deafness or blindness. That's why doxyPEP for syphilis matters so much."

DoxyPEP, which stands for doxycycline post-exposure prophylaxis, has been studied for about a decade as a prevention tool, including a seminal trial at UCSF in 2022. During that placebo-controlled trial, scientists had to end their study abruptly because the results were so positive that it became unethical not to offer doxyPEP to everyone.

Not long after, in fall 2022, San Francisco became the first city in the country to develop guidelines for providing doxyPEP to men who have sex with men and to transgender women, the two groups most at risk of STIs. Within a year of offering doxyPEP widely, rates of syphilis and chlamydia were down about 50% in those groups, according to the public health department. There was no change in gonorrhea.

The city has since expanded doxyPEP recommendations to include cisgender women. The drug generally is offered to people who have had repeated sexually transmitted infections or are otherwise at high risk of infection, possibly due to substance use or sex work.

"Broadening our criteria (to cisgender women) is important because chlamydia and syphilis are highly morbid in women," said Dr. Stephanie Cohen, head of HIV and STI prevention with the San Francisco Department of Public Health. If untreated, chlamydia can cause long-term pelvic pain and infertility, and "syphilis during pregnancy is a devastating situation," Cohen said.

"So there's a real public health imperative for us to make sure that everyone who can benefit from doxyPEP is included," Cohen said.

Authors of the Kaiser study, published this month in the Lancet, said their work was meant to better define how well doxyPEP works against gonorrhea and whether it was causing increased resistance. They were surprised that doxyPEP appeared to have lost all protection against gonorrhea over a relatively short period of time.

During trials, doxyPEP had only ever been mildly effective against gonorrhea - lowering the risk of infection by about 12% - but scientists did not expect that protection to disappear entirely after only a year of widespread use.

"The main takeaway is that while doxyPEP is a powerful prevention tool, it isn't a one-size-fits-all intervention," said Sara Tartof, an epidemiologist with the Kaiser Permanente Southern California Department of Research and Evaluation and an author of the study. "The effectiveness of doxyPEP differs substantially by infection type."

Scott agreed with that takeaway. He said that the robust protection against syphilis alone is worth keeping doxyPEP accessible, even if it is contributing to drug resistance in gonorrhea. He noted that doxycycline is not used to treat gonorrhea anyway, because of earlier problems with resistance.

"Gonorrhea developing doxy resistance? Whatever," he said. "It's not the end of the world. Resistance was already happening."

Similarly, Cohen said that when public health officials began rolling out doxyPEP, they already knew it wasn't working well against gonorrhea but were pleased with the results against other STIs. "I think folks in the field were never leaning on doxyPEP as a prevention strategy for gonorrhea," she said.

Scott heads an antimicrobial stewardship program at Stanford, which means he is responsible for the "judicious use of antibiotics and limiting the overuse of antibiotics," he said. "But I'm also a strong proponent of doxyPEP. The resistance story isn't a reason to abandon doxyPEP, but it's a reason to be thoughtful about how we use it."

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