A commonly used antibiotic could become a standard way to prevent sexually transmitted infections (STIs) such as chlamydia, syphilis and gonorrhea.
On October 2 the U.S. Centers for Disease Control and Prevention issued a draft guidance recommending that physicians prescribe doxycycline as a preventative therapy for certain people at high risk of acquiring STIs. If these guidelines go into effect, in addition to providing general sexual health counseling and STI screening, physicians could advise these individuals to take doxycycline as a postexposure prophylactic (PEP) after having unprotected sex. This strategy, known as doxy-PEP, “represents a new approach to addressing STI prevention,” the CDC wrote in a notice about the draft guidance.
The agency hopes that doxy-PEP, which can lower infection risk by half or more, could put a significant dent in the rising STI levels in the U.S. Between 2020 and 2021, the number of syphilis cases rose by 32 percent, while chlamydia and gonorrhea each rose by around 4 percent. “If we’re really honest about it, efforts to control STIs have failed, and we need to try something different,” says Edward Hook, an infectious disease researcher at the University of Alabama at Birmingham.
Scientific American talked with several experts about how well doxy-PEP works, why the CDC is not recommending it for everyone and what the risk of sexually transmitted bacteria becoming resistant to the drug is.
Who should take doxy-PEP?
Based on current evidence, the CDC is recommending that doctors only consider it for cisgender men who have sex with men (MSM), as well as for transgender women, when these individuals have had at least one STI within the past year. The prescription would be for a pill that would be taken once within 72 hours of unprotected sex.
The agency said that there is not enough evidence to recommend doxy-PEP to cisgender women and transgender men. That’s because few trials in this population have been completed to date. The only major study, conducted in 449 women in Kenya, found no significant reductions in STIs among those who took doxy-PEP, although hair analysis later showed that many of the women weren’t taking the antibiotic.
Jenell Stewart, an infectious disease physician at Hennepin Healthcare in Minneapolis, who led the trial in Kenya, says she agrees with the CDC’s recommendations, given current evidence. She adds that it’s possible doxy-PEP could work differently in men and women because different body parts are exposed to bacteria that go on to colonize the body in different ways. “We shouldn’t assume it’ll work the same in everyone,” Stewart says. Her team is now setting up more studies in the U.S. and Kenya to see whether doxy-PEP works in more populations.
What is the evidence for doxy-PEP?
Postexposure prophylaxis has long been used in HIV prevention: people at risk are advised to take antiviral drugs within 72 hours after unprotected sex. Researchers took a similar approach with doxycycline for STIs in several recent clinical studies—two conducted in France and one conducted in the U.S. The studies found that a single dose of doxycycline could more than halve the rate of bacterial infection in MSM and transgender women. The treatment was more effective against chlamydia and syphilis than gonorrhea.
The CDC has based its new recommendations on the design of the U.S. study, which focused on MSM and transgender women in Seattle and San Francisco who were at very high risk of acquiring STIs because they had frequent unprotected sex. “They’re the group that stands to benefit the most,” says study leader Annie Luetkemeyer of the University of California, San Francisco.
In a paper published in April in the New England Journal of Medicine, Luetkemeyer’s group tested doxy-PEP or a placebo in around 500 MSM and transgender women who had a median of nine sexual partners within a three-month period. The participants reported that 90 percent of their sexual encounters were unprotected, and each person had gotten at least one STI within the past year. Taking one dose of doxycycline within 72 hours of unprotected sex, Luetkemeyer found, reduced the risk of a bacterial infection by two thirds.
Are scientists concerned about doxy-PEP worsening antibiotic resistance?
Some experts worry that increased doxycycline use could drive antibiotic resistance in sexually transmitted pathogens. This is especially true of gonorrhea, which is particularly good at evading various antibiotics: around 25 percent of gonorrhea infections in the U.S. and the overwhelming majority of those in Kenya are already resistant to the class of antibiotics that includes doxycycline.
That could partly explain why one of the doxy-PEP studies in France, where around 60 percent of gonorrhea infections are resistant to antibiotics, found that the treatment had no significant impact on gonorrhea infection rates. “The issue of resistance in gonorrhea is not a matter of whether but when,” Hook says, although he adds he is an “enthusiast” about doxy-PEP in general.
So far there is little evidence that chlamydia and syphilis become resistant to antibiotics. Ongoing monitoring is needed, however. Scientists are also concerned that resistant bacteria could transfer genes that that confer antibiotic resistance to other bacterial species, which would be especially concerning because doxycycline is a go-to treatment for the bacteria that cause Lyme disease and leptospirosis.
Could taking doxycycline have unintended effects on a person’s microbiome?
Researchers are concerned that frequent doxycycline use could affect the normal, healthy bacteria that colonize the gut, vagina and other parts of the human body. This microbiome is involved in many aspects of health—everything from gut function to mental health—and disrupting the balance of bacterial species can affect these systems or lead to other infections. Luetkemeyer and Stewart both say they are testing rectal swabs and other samples from people in their study to see whether the antibiotic changed the assortment of bacteria that colonize various parts of the body.
What will happen when the CDC finalizes its recommendations?
In October 2022 San Francisco’s health department released its own guidelines supporting doxy-PEP in cisgender men and transgender women who have had a bacterial STI and have had unprotected sex with at least one cisgender man or transgender woman in the past year. Several other health departments, including California’s, have issued similar guidelines. Luetkemeyer says it will be helpful to have national guidelines, which will ensure that doctors everywhere know that doxy-PEP works and feel comfortable prescribing it. When health systems were developing guidelines for HIV prevention in the past, “we did a poor job of reaching the people who needed it most,” Luetkemeyer says. “Having guidelines helps start the dialog.”
Researchers are planning to continue testing doxy-PEP in different populations. If the approach proves successful, the CDC may expand its recommendations in the future to include cisgender women and men who have sex with cisgender women.
The CDC will receive comments on the draft guidelines until November 16, 2023, and has not said when it will release a final rule.
