A new study shows that taking a single dose of a commonly used, inexpensive antibiotic within 3 days of unprotected sex can help prevent chlamydia, syphilis and gonorrhea, three sexually transmitted infections (STIs). also known as sexually transmitted diseases or STDs) has been heard in the United States, Europe, and elsewhere for the past 2 decades.
The study, which included men who have sex with men (MSM) in San Francisco and Seattle, was stopped in May after an independent data monitoring board found that a strategy called doxycycline post-exposure prophylaxis (doxyPEP) reduced chlamydia and chlamydia risk. gonorrhea was more than 60%—therefore it was not necessary to continue the study. DoxyPEP also appeared to protect against syphilis, but the number of cases in the trial was too small to be statistically significant. The date will be revealed this week at the 24th International AIDS Conference in Montreal.
“It’s very exciting,” says Carlos del Rio, an HIV/AIDS physician and researcher at Emory University School of Medicine. But there are concerns that the regimen could cause the three bacteria that cause these diseases to become resistant to antibiotics, and scientists debate whether the data warrant doxyPEP’s introduction now. “It’s still a controversial topic,” says Jean-Michel Molina of Paris Cite University. “I don’t think we have enough information yet to recommend a strategy.”
Doxycycline, a sibling of the antibiotic tetracycline, has been around for more than 45 years and is commonly used to treat and prevent acne and Lyme disease. It also acts against parasites and is widely prescribed to prevent malaria in travelers. The drug usually has several side effects in addition to stomach upset and increased sensitivity to sunlight.
Prevention of bacterial STIs among MSM has become important in part because of the success of antiretroviral drugs against HIV, which has led to more condomless sex. Medicines can reduce the level of the virus in infected people so that they rarely pass it on, and taking them regularly before sex (PrEP) can protect uninfected people.
The idea for the new doxycycline study came from a small trial published in 2015. Fifteen MSM who were at high risk for STIs because of their sexual behavior and were taking medication for HIV infection added antibiotics to their daily pill regimen. At 48 weeks, compared with 15 similar MSM who were not given antibiotics, men taking doxycycline as PrEP had significantly fewer infections of three bacterial STIs. “It was promising as a pilot study,” says Jeffrey Klausner, an infectious disease specialist at the University of Southern California who led the trial.
Molina’s study in France, published in 2018, was based on the same idea, but with a slight difference: Doxycycline was used as PEP, not PrEP. Participants took the drug once, within 72 hours after sex without a condom. The team found that this reduced the risk of getting chlamydia or syphilis by 70% and 73%, respectively, but had no effect on gonorrhea.
The new study included 544 participants — mostly MSM, but also some transgender women and gender-diverse people — who were considered to be at high risk for STIs. Two-thirds of them were asked to follow the same protocol as in the French study. The remaining participants received standard STD testing and treatment. Everyone knew what group they belonged to. “We really wanted to do a real-world study,” says one of the lead researchers, Annie Luetkemeyer, an infectious disease physician at the University of California, San Francisco.
Leandro Mena, who heads the U.S. Centers for Disease Control and Prevention’s (CDC) division that monitors STIs, said he was “very excited” by the findings. “We want to be able to review the data in its entirety,” Mena says, but the CDC may soon issue preliminary guidelines about the regimen for high-risk populations.
The researchers argue that the benefits of doxyPEP do not outweigh the risk of antibiotic resistance. Neisseria gonorrhoeae, unlike the other two STD-causing bacteria, produces immediate resistance. (Molina suspects that doxyPEP may have stopped working against gonorrhea in France, because 81% of participants were resistant to it at the start of the study—almost double the prevalence seen in the new study.) DoxyPEP makes it worse, says Molina—“It’s absurd. .” What will happen to chlamydia and syphilis that are not yet resistant to antibiotics, “we don’t know, we hope,” he says.
The US team is still analyzing the antibiotic resistance data from the study. However, doxyPEP increases resistance N. gonorrhoeae, it has no practical effect because a different class of antibiotics is used to treat gonorrhea, notes Connie Selum, an epidemiologist at the University of Washington, Seattle, and one of the lead researchers. “I don’t see it as a huge disadvantage,” he says. In addition, doxyPEP is recommended for people at high risk of STIs, a relatively small group, he says.
Selum also participated in the doxyPEP study of Kenyan women who received HIV PrEP and had a disproportionately high rate of STIs. “We need an intervention now, and it’s a safe, inexpensive, well-tolerated drug that has few side effects,” he says. And treating those at high risk can help reduce the spread of STIs in the general population, Selum adds.
There may be other downsides to the strategy, however, points out Christopher Fairlie, head of the Melbourne Center for Sexual Health at Monash University in Clayton. Antibiotics, for example, can disrupt the bacterial microbiome in the gut, and resistance genes can jump between bacteria. Many gonorrhea and chlamydia infections cause no symptoms, clear up without treatment, and “have no meaning,” he adds. (Untreated syphilis, on the other hand, can damage the eyes, ears, and brain, causing miscarriages and stillbirths.)
But Klausner says the benefits outweigh the risks. He notes that some doctors who treat MSM prescribe doxycycline to protect against STIs. “Patients in the community know about it,” he says. “Now is the time to develop proposals.”