Taking doxycycline after sex reduces STI risk, study finds

  • by Liz Highleyman, BAR Contributor
  • Friday September 30, 2022
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Researcher Dr. Annie Luetkemeyer of UCSF led a doxyPEP trial that showed the antibiotic taken after sex reduces STI risk. Photo: Liz Highleyman
Researcher Dr. Annie Luetkemeyer of UCSF led a doxyPEP trial that showed the antibiotic taken after sex reduces STI risk. Photo: Liz Highleyman

Taking the antibiotic doxycycline as post-exposure prophylaxis (PEP) after sex can lower the risk of gonorrhea, chlamydia, and syphilis, according to a study presented at the recent International AIDS Conference in Montreal. San Francisco health experts discussed the findings and local implementation at the September 22 meeting of the Getting to Zero Consortium.

The DoxyPEP trial showed that gay and bisexual men and transgender women who were living with HIV or on PrEP reduced their risk of acquiring the three most common bacterial sexually transmitted infections by more than 60% if they took doxycycline within 72 hours after condomless sex.

"Using doxycycline after condomless sex has potential as an effective strategy to substantially reduce sexually transmitted infections in targeted populations with ongoing high rates of STIs," study investigator Dr. Annie Luetkemeyer of UCSF told the Bay Area Reporter.

"This isn't meant for everyone," Luetkemeyer said at an AIDS conference media briefing. "But there are populations that are really suffering from the STI epidemic, and it's time to take action on the data and really think about incorporating it into guidelines and rolling this out in a safe and thoughtful way."

As is often the case when it comes to LGBTQ health, San Francisco is taking the lead on doxycycline PEP implementation.

Current federal Centers for Disease Control and Prevention guidelines do not recommend for or against doxycycline PEP, but some providers are already offering it on a case-by-case basis, San Francisco City Clinic medical director Dr. Stephanie Cohen said at the Getting to Zero meeting.

The San Francisco Department of Public Health is developing interim guidance about who should be eligible for doxycycline PEP. Restricting eligibility could reduce access and increase disparities, but it would minimize unnecessary antibiotic use. DPH aims to build provider capacity, promote doxycycline PEP to appropriate communities, and roll it out in settings that serve people with high STI rates, Cohen said. Looking ahead, the agency will monitor the impact on STI incidence and antibiotic resistance.

"We're grappling with the risk-benefit ratio. There are some pros to taking a broader use approach and there are also some cons. We're trying to figure out the sweet spot," Cohen said. In the meantime, "It's helpful for patients and providers to have a conversation and make the choice that feels right for them with the information that we have available."

DoxyPEP study results

The DoxyPEP study recruited more than 500 men and transgender women who have sex with men at public health clinics in San Francisco and Seattle. About a third were living with HIV and the rest were taking PrEP. A majority had been diagnosed with an STI during the past year and they reported a median of nine recent sex partners.

The participants were randomly assigned to receive a single dose of oral doxycycline as post-exposure prophylaxis within 72 hours after condomless sex or the standard of care, which is regular testing and treatment after an STI diagnosis. They were tested for gonorrhea, chlamydia, and syphilis every three months.

The study was scheduled to run until May 2023, but it was halted a year early after an interim analysis showed that doxycycline PEP significantly reduced STI incidence.

Among people living with HIV, doxycycline reduced the likelihood of being diagnosed with any of these STIs by 62% per quarter compared with the standard of care (incidence of 12% versus 31%, respectively). The incidence of gonorrhea fell by 57%, chlamydia by 74%, and syphilis by 77%.

An even greater risk reduction was seen for HIV-negative participants on PrEP. In this group, there was an overall 66% reduction in quarterly STI incidence compared with the standard-of-care group (11% versus 32%). Gonorrhea dropped by 55%, chlamydia by 88%, and syphilis by 87%.

In both groups, doxycycline PEP was safe and well tolerated. However, doxycycline can cause side effects including gastrointestinal symptoms, irritation of the esophagus, and sensitivity to sunlight. Adherence was good overall. Just over half of the participants reported taking fewer than 10 doses of doxycycline per month, about a third took 10 to 20 doses, and 16% took more than 20 doses.

Advocates lauded the findings and urged prompt implementation.

"These are the kinds of innovations clinicians, patients, and communities desperately need to help fight the epidemic of STIs in the United States," David Harvey, executive director of the National Coalition of STD Directors, said in a statement. "Our takeaway from the DoxyPEP study is that we are shifting toward a future where symptomatic infection and community spread could be totally unnecessary for some of our highest risk neighbors and patients."

Doxy PEP concerns

Preventive use of doxycycline is not without concerns. One is that overuse of antibiotics can lead to drug resistance. But doxycycline is not typically used to treat gonorrhea or syphilis, meaning people who develop resistance will have other treatment options. What's more, a lower daily dose of doxycycline is used for weeks or months to prevent malaria in travelers without promoting resistance.

Another potential concern is whether frequent antibiotic use will disrupt the microbiome, the ecosystem of healthy bacteria that normally live in the gut, the vagina, and elsewhere in the body. Resistance and microbiome analyses are underway.

Leutkemeyer noted that people in the standard-of-care group had STIs so often that they spent a substantial portion of time on doxycycline treatment anyway. But using doxycycline as PEP instead of treatment reduces suffering and decreases the amount of time people can transmit the STIs.

As happened with HIV PrEP, some worry that doxycycline PEP could encourage people to have more condomless sex. "When PrEP came out, we saw a lot of shame and stigma — why not just use a condom? — but we need multiple tools," Leutkemeyer said. "I hope this won't come with the shame and blame that came with the first round of PrEP."

Equitable access will also be an issue. Inexpensive generic versions of doxycycline are widely available, but the cost could add up if people take it frequently. And everyone who could potentially benefit may not have access to sex-positive providers who know about the new intervention and will offer it without stigma.

A decade after its approval, Black and Latino men gay and bisexual men and cisgender women still are not using HIV PrEP as much as white gay men, and advocates fear the same could happen with doxycycline PEP. Preventive doxycycline could also work for cisgender women and transgender men, but it has not yet been studied in these populations. Dr. Connie Celum of the University of Washington said that a study of doxycycline PEP for cisgender women is now underway in Kenya.

The CDC is "encouraged" by the DoxyPEP data, according to a statement released in response to the study results. "It will be critical to provide guidance that will maximize effectiveness for STI prevention, while minimizing both individual and potential public health risks," the agency stated. "[I]t is our public health imperative to develop responsible guidance based on a careful consideration of all available data and public health risks and benefits — we cannot take shortcuts when it comes to people's health."

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