CDC finalizes doxyPEP guidelines for STI prevention

  • by Liz Highleyman, BAR Contributor
  • Wednesday June 5, 2024
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Dr. Annie Luetkemeyer. Photo: Liz Highleyman
Dr. Annie Luetkemeyer. Photo: Liz Highleyman

The federal Centers for Disease Control and Prevention has released guidelines for using the antibiotic doxycycline as post-exposure prophylaxis to prevent sexually transmitted infections — an approach known as doxyPEP — finalizing a draft issued last October.

According to the June 4 guidelines, the federal agency recommends that health care providers discuss the use of doxyPEP with all gay, bisexual, and other men who have sex with men and transgender women who have had chlamydia, gonorrhea, or syphilis within the past year. For other groups, providers are urged to use clinical judgment and shared decision-making.

"These final CDC recommendations provide important guidance on who may benefit from doxyPEP and practical guidance on prescribing, monitoring, benefits, and risks," Dr. Annie Luetkemeyer of UCSF, who co-led one of the major doxyPEP studies, told the Bay Area Reporter. "Clear national guidelines help programs, providers, and people who may be interested in doxyPEP use this new STI prevention tool safely and effectively and reach those who may benefit most."

DoxyPEP involves taking a single dose of doxycycline within 72 hours after anal, vaginal, or oral sex. It can be taken on consecutive days if sex is repeated, but no more than one dose in a 24-hour period. It is safe to use with HIV PrEP. Because it's an antibiotic, doxycycline does not prevent viral STIs such as HPV, herpes, or mpox.

The new guidelines are supported by findings from the DoxyPEP trial, first presented at the 2022 International AIDS Conference. The study 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. They were randomly assigned to receive a single dose of oral doxycycline after condomless sex or standard care, which is regular testing and treatment after an STI diagnosis.

The study was stopped 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 even greater in most cases: 55%, 88%, and 87%, respectively. Two French studies also showed that doxycycline reduced the risk of chlamydia and syphilis, though it was less effective against gonorrhea. But a study of cisgender women in Kenya found that doxyPEP failed to reduce the risk of STIs, possibly due to low adherence.

Preventive use of doxycycline is not without concerns, mainly that widespread use of antibiotics could encourage drug resistance. So far, however, researchers have not seen a marked increase in antibiotic resistance associated with doxyPEP, according to Luetkemeyer. 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.

Who benefits from doxyPEP

According to the new guidelines, published in the June 6 Morbidity and Mortality Weekly Report, providers should offer gay and bisexual men and trans women with a recent history of STIs a prescription for doxycycline so they can administer it themselves after sex. The prescription should include enough doses to cover anticipated sexual activity until the next visit. People prescribed doxyPEP should be tested for STIs every three to six months, and the ongoing need for doxyPEP should be reassessed on the same schedule.

The authors emphasized that doxyPEP "should be implemented in a context of a comprehensive sexual health approach, including risk reduction counseling; STI screening and treatment; recommended vaccination; and linkage to HIV PrEP, HIV care, or other services as appropriate."

Although it has not been directly tested in trials, the guidelines say that doxyPEP could also be discussed with men who have sex with men and trans women who have not had an STI within the past year if they expect to participate in sexual activities that are known to increase the likelihood of STI exposure.

The pharmacokinetics of doxycycline and its effectiveness for STI treatment suggest that doxyPEP should work for other groups, including cisgender women, cisgender heterosexual men, transgender men, and other queer and nonbinary people, according to the CDC guidelines. But because data from formal studies are lacking, providers "should use their clinical judgment and shared decision-making to inform use of doxyPEP with populations that are not part of CDC recommendations."

The San Francisco Department of Public Health issued the first local doxyPEP guidelines in October 2022. At the Conference on Retroviruses and Opportunistic in March, DPH researchers reported that the early rollout has already contributed to about a 50% reduction in chlamydia and early syphilis, though there was no significant change in gonorrhea.

San Francisco's doxy PEP guidelines are broader than the CDC's. They include transgender men along with cisgender gay and bisexual men and trans women, and apply to those who have multiple male sex partners even if they have not recently had an STI.

The California Department of Public Health goes further, saying providers can offer doxyPEP to all nonpregnant people at increased risk for STIs and to those who request it even if they have not previously been diagnosed with an STI or have not disclosed their risk status.

Implementation and access

The new guidelines were finalized after careful consideration of comments on the draft version from the public and experts, as well as consideration of the available scientific evidence, according to Dr. Laura Bachmann, acting director of the CDC's Division of STD Prevention, and Dr. Jonathan Mermin, director of the National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

"We believe this is the right step for right now to protect the nation's health, although we are constantly learning more about how to prevent STIs. We will continue to adjust our recommendations as additional data are available," Bachman and Mermin wrote in a letter to colleagues. "As always, we will provide updates as we learn more."

The new guidelines have generally been well received, but some clinicians and advocates have concerns about implementation and equitable access.

"The new CDC implementation guidance on doxycycline for STI prevention is an important and timely confirmation of the science behind doxyPEP," Dr. Jeffrey Klausner of the University of Southern California, and a former San Francisco deputy health officer, told the B.A.R. "Federal guidelines help support widespread use, reimbursement, and access, hopefully ensuring no one is left behind."

Mitchell Warren of AVAC, an advocacy group, added, "As with any new prevention option, it is essential for advocates to insist on and engage with user-centered, comprehensive and collaborative implementation programs and policies to help make sure the new CDC guidelines are translated into public health impact."

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