San Francisco is the first city to issue guidelines on the use of doxycycline post-exposure prophylaxis, or doxy-PEP, to prevent sexually transmitted infections, the Department of Public Health announced October 20. The interim guidance comes after study results showed that the inexpensive antibiotic lowers the risk of chlamydia, gonorrhea, and syphilis by more than 60%.
"We know that our community is very interested in taking advantage of this innovation in sexual health," San Francisco City Clinic medical director Dr. Stephanie Cohen told the Bay Area Reporter. "We're really hopeful that doxy-PEP can help us turn the tide on the STI epidemic that we've been struggling with in San Francisco and across the country for so long. We believe this is a really important, innovative public health strategy for STI prevention."
According to the new guidance, doxy-PEP is an option for cisgender gay and bisexual men and transgender women who have been diagnosed with a bacterial STI and who have had condomless anal or oral sex with at least one cis male or trans partner during the past year, as well as anyone with a history of syphilis.
This approach is supported by findings from the DoxyPEP trial, which were presented at the International AIDS Conference in Montreal this summer and at the September 22 meeting of the SF Getting to Zero Consortium.
As the B.A.R. previously reported, Dr. Annie Luetkemeyer of UCSF and colleagues recruited at public health clinics in San Francisco and Seattle more than 500 men and transgender women who have sex with men. About a third were living with HIV and the rest were taking PrEP. They were randomly assigned to receive a single dose of oral doxycycline 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 halted a year ahead of schedule after an interim analysis showed that doxy-PEP significantly reduced STI incidence. Among HIV-positive people, 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%). The incidence of gonorrhea fell by 57%, chlamydia by 74%, and syphilis by 77%. HIV-negative participants on PrEP saw an even larger 66% risk reduction compared with the standard of care group (incidence of 11% versus 32%). Gonorrhea dropped by 55%, chlamydia by 88%, and syphilis by 87%.
Doxycycline is generally safe, and it has few interactions with HIV medications, according to Cohen. However, it can cause side effects including gastrointestinal symptoms and sensitivity to sunlight, increasing the risk of sunburn.
"Doxy-PEP is the first biomedical prevention drug that has been shown to be effective and well-tolerated to reduce these infections," the DPH said in a statement. "In particular, doxy-PEP holds promise to decrease rates of syphilis in San Francisco, which are among the highest in the country."
Doxy-PEP implementation
The new guidance continues San Francisco's history of being at the forefront of innovations in HIV prevention and care. The city was the first in the U.S. to recommend antiretroviral treatment for everyone diagnosed with HIV — which both halts disease progression and prevents transmission of the virus — and gay and bi men in San Francisco were early adopters of PrEP.
A "handful" of local providers have already been prescribing doxy-PEP because they are aware of the data and their patients have requested it, Cohen said. Many of the approximately 250 San Francisco trial participants opted to continue doxy-PEP after they completed study follow-up.
Cohen estimated that around 5,000 city residents could be eligible for doxy-PEP based on having had an STI during the past year. In addition, some gay and bi men and trans women have multiple sex partners but have not recently been diagnosed with an STI. Providers can offer them doxy-PEP after explaining what is known and isn't known. Using broader eligibility criteria of all gay and bi men and trans women who are living with HIV or on PrEP, the number rises to around 35,000.
Doxy-PEP has not yet been studied for cisgender women and trans men, but a trial of cis women in Kenya is now underway. "I think this will provide the evidence base we need to make an informed decision about whether we can and should offer doxy-PEP to cis women. For now, we think there is insufficient evidence to make a recommendation," Cohen said. If a provider does offer doxy-PEP to at-risk cis women or trans men, they should test for pregnancy because doxycycline should not be used by pregnant people, she cautioned.
Preventive use of doxycycline is not without concerns. One is that overuse of antibiotics can lead to drug resistance. Another is whether frequent antibiotic use would disrupt the microbiome, the ecosystem of healthy bacteria that normally live in the gut and elsewhere in the body.
Leutkemeyer noted that people in the standard-of-care group in the DoxyPEP study had STIs so often that they spent a substantial portion of time on doxycycline for treatment anyway. But using doxycycline as PEP instead prevents symptomatic illness and decreases the amount of time people can transmit the STIs.
"This isn't meant for everyone," she 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."
To that end, the DPH worked with stakeholders including medical experts, local providers and advocates to develop the pioneering guidance. The federal Centers for Disease Control and Prevention and the California Department of Public Health do not yet have doxy-PEP guidelines, but both are considering it.
"We are really excited that we have the opportunity to offer this potentially highly impactful biomedical STI prevention tool to our community," Cohen told the B.A.R. "We've seen the impact biomedical HIV prevention tools can have with PrEP and treatment-as-prevention, but for so long we have not had such a tool for STIs.
"We know that we have a community that's very engaged in advocacy around sexual health and that has historically been enthusiastic about trying new interventions," she continued. "We're excited to work with the community to roll this out and see what impact it can have in San Francisco."
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