CDC issues first doxyPEP guidelines for STI prevention

  • by Liz Highleyman, BAR Contributor
  • Wednesday October 4, 2023
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Dr. Annie Luetkemeyer of UCSF co-led a doxyPEP trial and presented findings at the 2022 International AIDS Conference. Photo: Liz Highleyman
Dr. Annie Luetkemeyer of UCSF co-led a doxyPEP trial and presented findings at the 2022 International AIDS Conference. Photo: Liz Highleyman

The federal Centers for Disease Control and Prevention issued its first proposed guidelines for using the antibiotic doxycycline as post-exposure prophylaxis to prevent sexually transmitted infections, an approach known as doxyPEP. The draft will be open for public comment for 45 days.

The guidelines, published October 2 in the Federal Register, state that a single 200 milligram dose of oral doxycycline taken within 72 hours after sex should be considered for gay, bisexual, and other men who have sex with men and for transgender women who have had gonorrhea, chlamydia, or syphilis at least once during the past year.

Due to a lack of evidence, "no recommendation can be given at this time" on the use of doxyPEP for cisgender women, cisgender heterosexual men, transgender men, or other queer or non-binary individuals, the proposed guidelines add.

According to the guidelines, doxyPEP "should be implemented in the context of a comprehensive sexual health approach including risk reduction counseling, STI screening and treatment, recommended vaccination, and linkage to HIV pre-exposure prophylaxis (PrEP), HIV care, or other services, as appropriate."

The new prevention intervention makes its debut at a time when STI rates are rising steeply in the United States, though San Francisco saw a drop in 2022, especially in syphilis cases. It is not yet clear whether the city's early rollout of doxyPEP has contributed to the decline.

"It is really essential to have national guidelines to make providers aware of doxyPEP, who may benefit from this new prevention tool, and how to approach providing it safely," Dr. Annie Luetkemeyer of UCSF told the Bay Area Reporter. "Guidelines are an important first step to address equitable access for those who are most impacted by recurrent STIs and who may be at risk for lack of access, given existing health disparities."

DoxyPEP research

The draft guidelines are supported by results from the DoxyPEP trial, led by Luetkemeyer and Dr. Connie Celum of the University of Washington. The study, first presented at the 2022 International AIDS Conference, enrolled 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.

The participants 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 following an STI diagnosis.

The study was scheduled to run until May 2023, but it was halted a year early after an interim analysis showed that doxyPEP significantly reduced STI incidence. For people with HIV, doxycycline reduced the risk of acquiring gonorrhea by 57%, chlamydia by 74%, and syphilis by 77%. For those on PrEP, the risk reduction was 55%, 88%, and 87%, respectively.

The French DoxyVAC trial also showed that doxycycline after sex reduced the risk of acquiring the three STIs. In both studies, adherence was good and doxycycline was generally safe and well tolerated, though the drug can cause side effects including gastrointestinal symptoms, irritation of the esophagus, and sensitivity to sunlight.

However, a study of cisgender women in Kenya found that taking doxycycline after sex did not significantly reduce the risk of STIs in this population. Although the drug appeared to reach adequate concentrations in vaginal and cervical tissue, many participants reported that their adherence was "imperfect," suggesting that doxyPEP might protect women if they use it more consistently.

The CDC guidelines recommend doxyPEP for cisgender men who have sex with men and transgender women with a history of STIs, the group with the strongest evidence of benefit, but "they leave the door open for other populations," Luetkemeyer said.

"We don't have data for men who have sex with women, and we don't have data to support its use in cisgender women yet. However, clinicians can use the guidance to have a case-by-case discussion with people who aren't included in the recommendation to decide if doxyPEP makes sense while we are learning more," she added. "The CDC could have stated that doxyPEP should not be given to anyone outside of the recommendation, but that would be overly narrow."

Preventive use of doxycycline is not without concerns. One is that widespread use of antibiotics could lead to drug resistance, although this did not appear to be a clinically significant problem in studies to date. Another is that frequent antibiotic use could disrupt the microbiome, the ecosystem of healthy bacteria that normally live in the gut and elsewhere in the body. The CDC guidance states that these potential risks "will need to be closely monitored."

Equitable access will also be an issue. Inexpensive generic doxycycline is widely available, but the cost could add up if people take it frequently. What's more, everyone who could potentially benefit from doxyPEP may not have access to sex-positive providers who know about the new intervention and will offer it without stigma, advocates noted.

DoxyPEP in San Francisco

In keeping with its pioneering role in promoting LGBTQ sexual health, San Francisco was the first city to issue doxyPEP guidelines last October. Since then, more than 3,000 residents have used doxyPEP, according to the SF Department of Public Health.

"We know that our community is very interested in taking advantage of this innovation in sexual health," SF City Clinic medical director Dr. Stephanie Cohen told the B.A.R. at the time. "We believe this is a really important, innovative public health strategy for STI prevention."

San Francisco's doxyPEP recommendation is broader than the CDC's, including cisgender gay and bisexual men, transgender women and transgender men who have had multiple male or trans woman sex partners during the past year, even if they have not previously been diagnosed with an STI. Based on these criteria, Cohen estimated that around 35,000 city residents could be eligible for doxyPEP.

"We are pleased to see the CDC release draft national guidelines for the use of doxyPEP for prevention of chlamydia, gonorrhea, and syphilis. We are also proud to be the first health department in the nation to issue guidance and recommendations for doxyPEP," SF DPH said in a statement sent to the B.A.R. "Many providers and community members in San Francisco have embraced this welcome advance in the field of sexual health."

"SF DPH has been offering doxyPEP to clients who meet eligibility criteria in our citywide guidance with a focus on equitable access, resulting in high rates of interest and uptake across race and ethnicity relative to the population," the statement continued. "We remain committed to working with our SF Health Network clinics and community-based organizations so that doxyPEP, and all sexual health services and resources, reach previously underserved communities."

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