A US health department became one of the first to recommend that people at risk of contracting a sexually transmitted infection (STI) take a preventive course of antibiotics after unprotected sex. Clinical trials have shown that this strategy can reduce infections such as chlamydia, syphilis, and gonorrhea. But some researchers worry that it will contribute to antibiotic resistance.
Last month, the San Francisco Department of Public Health recommended that people at risk of infection take a shot of the antibiotic doxycycline after unprotected sex to prevent a bacterial STD.
Rates of bacterial STIs have risen steadily over the past decade, particularly in men who have sex with other men (MSM). “We don’t have any tool to reduce the rate [bacterial] sexually transmitted diseases, except for asking people to use a condom,” including oral sex, says infectious disease doctor Jean-Michel Molina at the University of Paris.
Molina led the first trial1 of doxycycline post-exposure prophylaxis—a preventive treatment strategy known as doxyPEP—which reported results in 2018. In that trial, 22% of those using doxycycline and 44% of those who didn’t had a sexually transmitted infection became infected over a period of time. nine months. The use of antibiotics led to a 70% reduction in chlamydial infection and a 73% reduction in the incidence of syphilis in the participants. Gonorrhea infections were not significantly reduced.
DoxyPEP is similar to the highly successful strategy of taking antiretrovirals before unprotected sex to prevent infection with HIV — known as HIV-PrEP. Taking HIV-PrEP reduces the risk of contracting HIV from sex by about 99%.
The success of the experiment
San Francisco adopted the policy after presenting the interim results of another trial — called DoxyPEP — at the International AIDS Conference in Montreal in late July. This trial, which included men who have sex with men and transgender women either living with HIV or taking HIV-PrEP, was stopped early because taking doxycycline after unprotected sex was so effective in reducing morbidity sexually transmitted. Everyone enrolled in the trial, led by infectious disease physician Annie Lutkemmer at the University of California, San Francisco, was then offered doxyPEP. Chlamydia and syphilis infections were 70% lower, and gonorrhea infections were 55% lower in each three-month period in those who took doxyPEP. In people who did not take doxyPrep, about 30% developed one or more STDs per quarter.
Syphilis in men can cause serious health problems, such as blindness and nerve damage if left untreated. Chlamydia and gonorrhea infections in men are rarely serious, but in women, they can lead to infertility. Syphilis can be transmitted to unborn children and cause miscarriage, stillbirth, or brain and organ damage in children born with the disease.
But researchers are divided on whether the evidence of efficacy in MSM alone is enough to make a decision to officially release doxyPEP. More data from multiple trials are needed to show whether doxyPEP is driving antibiotic resistance, says Manik Kohli, a sexual health physician and researcher at University College London.
Other jurisdictions are taking a more cautious approach than the San Francisco Department of Public Health, which has not responded natureComment request. The UK’s Health Security Agency and the British Association for Sexual Health and HIV have stated that they do not endorse the doxyPEP strategy for preventing syphilis or chlamydia, in part due to a lack of data on antimicrobial resistance.
Face the resistance
When exposed to antibiotics, bacteria that carry resistance can spread and survive. Using doxycycline to prevent infection greatly increases a person’s exposure to the antibiotic, which can lead to resistance, says Chris Kenyon, a microbiologist at the Institute of Tropical Medicine in Antwerp, Belgium. In the DoxyPEP trial, some participants took more than 20 doses of doxycycline each month, an amount Kenyon describes as “astronomical.”
Doxycycline is a “crucial” antibiotic for treating other conditions, including the skin infections they cause Staphylococcus aureus and bacterial pneumonia, says Kenyon. DoxyPEP can lead to the emergence of antibiotic resistance in the bacteria that cause these infections and limit treatment options, he says.
He says health care workers should take a precautionary approach when prescribing antibiotics as a preventive treatment, especially among men who have sex with men. They are the main population for the emergence of antibiotic resistance if antibiotic use is high, because people tend to have multiple partners and networks that increase the chance of spreading resistant bacteria. Sex workers are another category in which antimicrobial resistance has emerged in the past.
Resistance to antibiotics of the tetracycline class, which includes doxycycline, is already common for gonorrhea. In the United States, about 25% of gonorrhea cases are caused by bacteria that are resistant to tetracycline. Elsewhere, resistance rates are rising, with studies suggesting rates approaching 60% or 70% in Europe1And the3.
Molina predicts that doxyPEP’s efficacy against gonorrhea will depend on resistance rates in the community and will likely decrease over time as resistance levels rise.
But Luetkemeyer says early results from a second French trial, called DOXYVAC, show that doxycycline reduces gonorrhea infections — despite high levels of resistance. The results indicate that the drug can still prevent infection from occurring, even if it is not effective in treating a proven infection. “It often takes much less medication to prevent disease than it does to treat disease,” she says.
Doxycycline resistance has not been shown in chlamydia or syphilis. Molina says it could take years to find out if doxyPEP leads to resistance to these infections.
Luetkemeyer and her colleagues collected swab and stool samples to see if people using doxycycline as a preventive tool altered the community of microorganisms living in the gut or increased antibiotic resistance. These findings will be presented at a conference in February 2023. Luetkemeyer also notes that there are other sources of doxycycline in the community that could contribute to resistance.
One hope is that use of doxyPEP in men who have sex with men can lower rates of STI infection in the broader community — including women, who bear the greatest effects of chlamydia and gonorrhea infections — just as HIV-PrEP did for HIV. people in high-income countries.
But Kenyon doubts doxyPEP will lower rates of STDs, which can remain stubbornly high even after large-scale interventions. In the late 1990s, a mass treatment campaign with the antibiotic azithromycin to eradicate an outbreak of syphilis in Vancouver initially lowered rates, but they soon rebounded.2.
Since Molina and colleagues published the results of the first doxycycline study in 2018, people have used doxycycline off-label as a preventive tool, he says. Kenyon fears that doxyPEP could expose people to antibiotics for years or even decades.
For people already using doxyPEP, public health recommendations are unlikely to convince them to stop, says Kohli. After Luetkemeyer’s presentation at the International AIDS Conference in July, the US Centers for Disease Control and Prevention published information to guide the use of doxyPEP. An agency spokesperson said the agency will publish ex post guidance when final data is published and reviewed nature.
Guidelines about use are important for informing people of the safety of a strategy they may already be using, and for making prevention treatment available for people who may not be in a position to advocate for doxyPEP on their own, says sexual health physician Jenelle Stewart at Hennepin Health Care in Minneapolis, MN. Stewart is leading a doxycycline prophylaxis trial in Kenya for women taking HIV-PrEP4.
Despite the unknowns, Stewart says the benefits outweigh the risks. “People should be able to access this tool, if it makes sense for them and their lifestyle,” she says.