Public health officials are deploying a powerful new weapon in the war against rising sexually transmitted infections: a common antibiotic that works as a morning-after pill.
It is the latest advancement as the sexual health field shifts to preventive medicine — not just condoms, abstinence and tests — as the best hope for quashing the pathogens that can spread during sex.
For the past decade, people have been able to have unprotected sex with a low risk of contracting HIV thanks to daily pills known as PrEP, or pre-exposure prophylaxis. But they were still susceptible to bacterial bugs, including the recent spike in syphilis, gonorrhea and chlamydia — until now.
Recent studies show the antibiotic doxycycline taken after sexual encounters works as a post-exposure prophylaxis to prevent those infections. But experts are also worried about unintended consequences. The Centers for Disease Control and Prevention plans to release guidelines later this summer for deploying the treatment, known as DoxyPEP, in hopes of addressing fears among medical professionals that preventive use would fuel antibiotic resistance — and the rise of drug-resistant superbugs.
“It’s the first major intervention we’ve had for STIs since the vaccine for human papillomavirus,” nearly two decades ago, said Jonathan Mermin, who leads STI prevention for the CDC. “But it is a new intervention, and because of that, there are potential benefits and potential risks.”
Doctors, public health officials and sexual health clinics have embraced preventive pills as a realistic way to curb STIs because they preserve pleasure while protecting partners. Some doctors have started prescribing it to a narrow segment of the gay community considered at elevated risk for STIs.
“Just like PrEP was a game changer, this empowers individuals to make choices about their sexual health,” said Jorge Roman, senior director of clinical services at the San Francisco AIDS Foundation, one of the first to widely distribute DoxyPEP. “It doesn’t always have to be about condoms.”
Doxycycline is already used as a front line antibiotic treatment for chlamydia and occasionally for syphilis and gonorrhea. But its use for prevention has drawn concerns that it would no longer be effective in patients who use it regularly and that it may facilitate the evolution of antibiotic resistant strains of the pathogens.
The drug’s proponents say these concerns are overblown because the criteria for eligibility are often narrow: Transgender women and men who have sex with men — and only if they have condomless sex and contracted an STI in the preceding year.
Those were the demographics recruited for a study of 500 patients in San Francisco and Seattle that found DoxyPEP effective. The study found a roughly 65 percent reduction in syphilis, gonorrhea and chlamydia cases in those who used the antibiotic between 2019 and 2022, mirroring similar results from European studies.
Another study of DoxyPEP use by cisgender women in Kenya between 2020 and 2022 did not find the treatment effective, a result that surprised and stumped researchers. Anatomical differences could play a role, but health officials say other studies suggest doxycycline becomes concentrated enough in vaginal fluid to confer protection against STIs.
Experts say it’s too early to conclude that DoxyPEP won’t work for women and more research is needed. Another possible explanation is women enrolled in the Kenyan study may not have consistently used doxycycline after sex. Researchers note early studies that found PrEP ineffective in protecting African women from HIV were eventually explained by poor adherence to the drug regimen rather than biological differences.
Researchers studying DoxyPEP are scrutinizing whether it could also render antibiotic treatments less effective. The U.S. study found a slight increase in antibacterial resistance, which the study’s authors said merits long-term attention. But they also said the finding should be tempered by the fact doctors would also be administering fewer antibiotics if people avoid catching and spreading STIs.
David Hyun, director of the Antibiotic Resistance Project at The Pew Charitable Trusts, said he was concerned by patients in the study using DoxyPEP as frequently as 20 times a month. More data is needed to understand the long-term effects — for individuals as well as broader communities, he said.
“If you keep exposing a patient to antibiotics like doxycycline, you are raising the risk of that patient being colonized or infected with a resistant strain sometime in the future,” Hyun said.
Some LGBTQ+ health providers suspect doctors may be using antibiotic resistance concerns to mask discomfort with condomless gay sex. They note that syphilis has yet to become resistant to penicillin since the antibiotic became the front-line treatment for the STI in the 1940s. And they point out doxycycline is widely used for other reasons, including long-term acne treatment and malaria prevention.
“We have used doxycycline for multiple other things,” Shira Heisler, medical director of the Detroit Public Health STD Clinic, said during a May conference of the National Coalition of STD Directors. “And I think specifically now being like, ‘We are not going to do it because of antimicrobial resistance’ when it’s specifically related to STIs is a good time to call out, ‘This is what stigma is. This is what bias is.’”
Proponents of DoxyPEP said it offers a long-needed solution to a spike in STIs. The CDC recorded more than 2.5 million cases of syphilis, gonorrhea and chlamydia in 2021, up from 1.8 million in 2011.
In 2021, 36 percent of syphilis and gonorrhea cases were in men who have sex with men, according to the CDC. The CDC says these disparities cannot be explained by differences in sexual behavior alone. When people have a smaller pool of potential sexual partners with higher rates of STIs, they are more likely to have sex with someone with an infection. Cases in cisgender women and heterosexual men have also been rising.
Experts say everyone would benefit from DoxyPEP being limited to those most at risk because that would break chains of transmission early and reduce the likelihood of infections spreading more broadly.
Some physicians say allowing people to have worry-free sex is a worthy goal on its own.
“My goal as a physician is to make sure my patients are able to have whatever type of sex they want and however much sex they want as safely as possible,” said Boghuma Kabisen Titanji, an infectious diseases specialist in Atlanta. “And if DoxyPEP would allow them to do it, then I have no problem offering it.”
Nick, a 35-year-old resident of Lafayette, Ind., said he recently started taking DoxyPEP for peace of mind, knowing he would be less likely to get an infection as he has frequent condomless sex.
HIV was no longer a concern because he has been taking PrEP for a decade, said Nick, who spoke on the condition that his last name not be used to candidly discuss his sex life. But he has endured uncomfortable bouts of syphilis and chlamydia.
“If you are taking HIV PrEP, why not take another extra kind of safeguard too?” he said. “It’s like a security blanket.”
As the country considers how widely to distribute DoxyPEP, public health officials and activists are worried it will be the latest medical advancement to roll out in an inequitable way, following similar racial gaps seen with PrEP and mpox vaccinations. Federal officials say PrEP users are disproportionately White even though most new HIV cases are in Black and Latino people. The CDC estimates that most mpox cases have been in Black and Latino men, but only a third of vaccine doses have gone to them.
LGBTQ+ health providers are already reporting disparities, with White patients more likely to ask about DoxyPEP and Black and Latino patients less likely to be familiar with it.
During a discussion about DoxyPEP at the STD conference, one state health official noted that those who can afford to travel to Puerto Vallarta, a popular vacation destination among some gay Americans, can buy doxycycline to stockpile for themselves and their friends because the antibiotic is available over the counter in Mexico. But experts say concerns about antibiotic resistance would make it difficult for over-the-counter sales to occur in the United States.
Mermin, the CDC official, said equity is a top concern as the agency crafts its guidance for the use of DoxyPEP. It would be essential to ensure the medication is available in clinics serving people at the highest risk for STIs, he said, and to raise awareness outside of medical settings, such as on dating apps.
In London, Joey Knock said he started buying DoxyPEP outside of official channels, a common practice among some gay Europeans, last winter after regular bouts of gonorrhea.
But he limits his use to higher-risk nights, such as when he has unprotected sex in dark rooms with strangers.
“I’m someone who was averaging an STI a month,” said Knock, 33. “I’ve done the risk analysis for me, but it also benefits other people if me taking DoxyPEP means I don’t get chlamydia, then I don’t pass chlamydia around.”
In San Francisco, the first major jurisdiction where public health officials recommended DoxyPEP, providers noticed patients taking a similar approach: Using it after higher-risk sexual encounters rather than every encounter.
“We need to do more analysis to see if that could be making DoxyPEP less effective or if perhaps people are making really good decisions about when to use it,” said Stephanie Cohen, who leads STI prevention for the San Francisco Department of Public Health.
The San Francisco AIDS Foundation, which says it has connected more than 1,800 people to DoxyPEP, does not limit the antibiotic to people who have recently contracted a sexually transmitted infection, but counsels patients on the unknown risks of antibiotic resistance.
Anu Hazra, co-medical director of the Howard Brown Health, an LGBTQ+ health provider in Chicago, said antimicrobial resistance is “probably the largest public health threat we have” but doxycycline for a small group of people pales in comparison to the rampant use of antibiotics in the meat industry and other sectors.
He and other experts say vaccines to prevent STIs could be another game changer that does not carry the same baggage as antibiotics. A recent study showing that a vaccine for meningitis can also reduce the likelihood of contracting gonorrhea offers promise on that front. But DoxyPEP offers an immediate solution to an ongoing problem and could be pared back if antibiotic resistance emerges, Hazra said.
“We are seeing rising rates of STIs across the board for nearly a decade now. What we are doing now is not working,” Hazra said. “We need to try something new.”
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