As the United States reckons with a burgeoning sexually transmitted disease crisis, a broadening chorus of public health experts are calling for the Centers for Disease Control and Prevention to endorse prescribing a preventive antibiotic pill to gay and bisexual men and transgender women at high risk of STDs.
But while a growing body of research shows that taking doxycycline after sex substantially lowers STD infection rates in this population — though not in cisgender women, according to the findings of a highly anticipated new study — some experts remain concerned that widespread use of the antibiotic for this purpose could do more harm than good by fueling the global crisis of antibiotic-resistant infections and harming people’s microbiomes.
“There’s going to be a very rigorous debate about whether this is a good idea, and for whom,” said Dr. Matthew Golden, director of the HIV and STD program in Seattle’s health department.
That debate has been at the forefront of the annual Conference on Retroviruses and Opportunistic Infections, which started Sunday in Seattle, with new findings from several studies of doxycycline for STD prevention unveiled Monday.
This includes the third randomized trial to find that instructing gay and bi men (one of the previous trials also included trans women) to take the antibiotic within 72 hours of sex without a condom — a protocol known as doxycycline post-exposure prophylaxis, or doxyPEP — lowers the risk of bacterial STDs. The new study, conducted in France, randomized about 500 gay and bi men to receive doxyPEP or no antibiotics and found doxycycline lowered the rates of gonorrhea, chlamydia and syphilis by 51% to 89%.
Another study found that in one of the other major doxyPEP trials, there was no marked increase in doxycycline resistance among three key bacteria, including gonorrhea and staph. However, this is not likely to resolve the ongoing debate on the matter.
Less controversial among public health experts is the potential for using a vaccine for STD prevention. The French study further found that a meningococcal B vaccine halved new gonorrhea infections.
The Seattle conference also saw findings from a randomized study of cisgender women in Kenya in which doxyPEP had no impact on their STD rates. Calling the study’s results “very disappointing,” its director, Dr. Jenell Stewart, an infectious disease physician at the University of Minnesota, said differences in anatomy, antibiotic resistance and adherence to the medication protocol could each at least partially explain the lack of efficacy in women while doxyPEP has consistently worked well in gay men in Western nations.
The new efficacy research shared Monday builds on previously released findings that in recent years have fueled increasing excitement within the infectious disease field over doxycyline’s promise as an answer to out-of-control STD transmission.
One study, conducted in Seattle and San Francisco and presented at a July conference, saw about a two-thirds overall reduction in STDs among gay and bi men and trans women. A previous French study, published in 2017, found the intervention dramatically cut syphilis and chlamydia infections, but did not affect gonorrhea.
“The data show in men a consistent benefit in terms of reducing the incidence of bacterial STIs,” Dr. Jean-Michel Molina, the lead author of both of the French studies and an LGBTQ health researcher at the Université Paris Cité, told NBC News, referring to the term sexually transmitted infections. He added that more research is needed to confirm the efficacy of the vaccine for gonorrhea.
Paul Marcelin, 48, a software engineer living in Alameda, California, participated in the Seattle-San Francisco study and was randomized into the control group that did not receive the antibiotic. After the study was discontinued early due to high efficacy, he was offered doxyPEP last summer.
“It’s been very, very positive, having that as an extra source of peace of mind,” Marcelin said of his experience taking doxycycline for prevention, noting that he typically contracts an STD about once every two years and has had none since starting doxyPEP. “It’s just part of my health routine.”
Gay and bi men, plus transgender women, have been the focus of most of the recent research into pharmacological prevention of STDs, because they have a higher rate of such infections than cisgender heterosexual people (lesbians, meanwhile, have lower rates than heterosexual people). Men who have sex with men, for example, comprise less than 2% of the U.S. adult population but, according to the CDC, account for more than 40% of U.S. syphilis diagnoses.
Over the past two decades, gonorrhea, chlamydia and syphilis have soared, to 2.5 million cases in 2021. The CDC estimates this has saddled the nation with $1.1 billion in direct medical costs.
Most critically, syphilis — a scourge that was nearly eliminated in late 1990s but that the CDC reports skyrocketed by 68% between 2017 and 2021, to 171,000 cases — poses a potentially fatal threat to infants born to undiagnosed women. In rare cases, it can also harm vision or even cause blindness.
David Harvey, executive director of the National Coalition of STD Directors, said the overall infection surge is driven, in part, by federal cuts to state STD programs.
Condom use among gay and bisexual men in particular has also seen a long decline since HIV became treatable, and thus less frightening, in 1996, and with the advent a decade ago of the HIV prevention pill, known as PrEP.
Harvey, like many other public health experts, is looking to doxycycline, which typically costs pennies per pill, as a potent tool that could help turn the STD tide.
Some infectious disease experts, however, remain gravely concerned that doxyPEP adoption could fuel the emergence of drug-resistant pathogens, especially staph.
“Overall, my biggest fear is they’re not thinking about global antimicrobial resistance,” Fabian Kong of the University of Melbourne said of doxyPEP’s champions. “They’re just thinking about the STI world.”
The World Health Organization lists antimicrobial resistance as one of the top 10 global public health threats facing humanity.
Approved in the 1960s, doxycycline is prescribed widely to treat acne and rosacea, to treat or prevent Lyme disease, and to prevent malaria among travelers and the military. Other tetracyclines, the antibiotic class to which doxycycline belongs, have long been used in livestock production — to the concern of many infectious disease experts, who worry this fuels drug-resistant infections that can affect humans.
For doxyPEP, such concern is perhaps less crucially relevant to the three major STDs themselves. There is no evidence that chlamydia has acquired resistance to tetracyclines and only scant evidence that syphilis has. Plus, the drug class is not used to treat gonorrhea. However, some experts believe it is possible that doxyPEP’s use could drive up the existing resistance in gonorrhea strains, potentially making the intervention’s ability to prevent that STD short-lived.
But by reducing the spread of STDs, some experts argue, doxyPEP could also lead to less antibiotic use to treat such infections and less spread, possibly mitigating the emergence of drug-resistant strains.
The CDC has issued increasingly urgent warnings in recent years about gonorrhea’s potential for evading the last remaining simple and effective antibiotic treatment for the infection.
Dr. Annie Luetkemeyer, a professor of medicine at the University of California, San Francisco, presented findings at the retrovirus conference regarding a subset of the 637 participants in the Seattle-San Francisco study. The researchers did not find marked increases among them in doxycycline resistance to three bacteria: Neisseria gonorrheae, Staphylococcus aureus and non-pathogenic Neisseria. These findings are limited by the fact that the participants were followed for no more than a year, there were not many samples of gonorrhea to test, and some of those in the control group received doxycycline to treat STDs.
“I don’t think any of the resistance findings are a showstopper yet for doxyPEP,” Luetkemeyer said. “However, we will need to thoughtfully monitor for resistance in STIs and off-target bacteria like Staph aureus to understand doxyPEP’s impact over time.”
Luetkemeyer and her colleagues also found that those who were given doxyPEP ultimately received 50% less of the standard antibiotic treatment for gonorrhea, ceftriaxone, due to fewer infections.
Kong and other experts are also concerned about the impact routine doxycycline use may have on people’s microbiomes. Luetkemeyer said this is a challenging question to answer, and one that she and her colleagues are continuing to study, along with the antimicrobial resistance concern.
The future of doxyPEP
Concerns about drug resistance and the microbiome notwithstanding, some infectious disease experts say the time is ripe for the CDC to endorse a rollout of doxyPEP among certain gay men and trans women.
Dr. Jeffrey Klausner is an infectious disease expert at the University of Southern California and an author of several papers on doxycycline as STD prevention. Proposing providing doxyPEP only to those most at risk of STDs, he said, “It’s really a drop in the ocean of tetracycline use, but it could have a substantial benefit on sexually transmitted infections.”
A 2018 study found that over a two-year period, only 0.1% of those 13 to 65 years old in Massachusetts had more than one STD, and this small group of only 7,000 people accounted for 28% of all STDs in the state during this time period.
Michael Traeger, a research fellow at Harvard Medical School, presented a modeling study at the Seattle conference in which he and his colleagues reviewed patient data at the LGBTQ-focused clinic Fenway Health in Boston and identified what they characterized as an efficient prescribing strategy to minimize antibiotic use while maximizing impact: Give doxyPEP for 12 months to gay and bi men who had recently had an STD. This, they projected, could prevent up to 42% of subsequent STDs in the overall patient population.
Even in the absence of formal CDC guidance, some gay men are already taking doxycycline for STD prevention. And in October, the San Francisco Department of Public Health became the first in the nation to establish interim doxyPEP guidelines. Plus, certain LGBTQ-focused clinics, including Howard Brown Health in Chicago and the Los Angeles LGBT Center, have recently adopted such protocols, or will soon.
“We should not conflate antibiotic prophylaxis with antibiotic misuse,” said Dr. Anu Hazra, a physician at Howard Brown who is among those in the public health field calling for the CDC to establish doxyPEP guidelines. “We use antibiotics as prophylaxis for many different diseases and conditions where data support its use.”
According to Dr. Leandro Mena, the CDC’s director of STD prevention, the agency has already begun laying the groundwork for potentially establishing doxyPEP guidelines. He said that once the Seattle-San Francisco study is published, likely by spring, this effort will advance and will include a review of the relevant science as well as expert and community input — likely a monthslong process.
“We know that it works,” Mena said of doxyPEP. He said the CDC is concerned with assessing the intervention’s safety, deducing “which populations can benefit the most” and addressing equity concerns, considering that people of color contract STDs disproportionately.