The Centers for Disease Control and Prevention is proposing a new policy aimed at dramatically reducing sexually transmitted infections in the United States.
In a guidance document published Monday in the Federal Register, the CDC is seeking input on its proposal that health providers offer gay and bisexual men who have sex with men, as well as transgendered women, access to a common antibiotic, doxycycline, that they could take after having had unprotected sex to lower their risk of acquiring chlamydia, gonorrhea, or syphilis. Doxycycline is in the tetracycline family of antibiotics.
Studies have show the so-called “doxy PEP” regime — a single, 200-milligram dose taken no later than 72 hours after unprotected sex — can reduce acquisition of chlamydia and syphilis by nearly 80%, and gonorrhea by about 50%. PEP is short for post-exposure prophylaxis.
“Doxy PEP is moving STI prevention efforts into the 21st century,” Jonathan Mermin, director of CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention, said in a statement. “We need game-changing innovations to turn the STI epidemic around, and this is a major step in the right direction.”
The CDC, which has been working on the guidance for over a year, is asking for comments on the proposed guidance over a 45-day period.
Connie Celum, co-principal investigator of one of the trials, DoxyPEP, said the goal of the strategy is to reduce the STI risk in a specific group: gay and bisexual men and transwomen who have unprotected sex with other men.
“One of the things that I think sometimes gets lost in the discussion is, this is not an intervention for everyone, but one for people who are particularly high risk,” Celum, who is director of the International Clinical Research Center at the University of Washington, told STAT in an interview.
Several studies have explored the efficacy of the regimen. Some of the trials were stopped early because they were so clearly effective. One, the IPERGAY trial in France, published in Lancet Infectious Diseases in 2018, did not see a reduction in gonorrhea cases. But Celum said that may have been because there is a substantially higher rate of tetracycline resistance in gonorrhea bacteria in France (over 60%) as compared to in the U.S. (25%).
In the DoxyPEP study, the researchers divided the cohort of men and transgendered women into two groups: Those who were given doxycycline to take after unprotected sex and those who were not. (The two groups were further divided into people who were living with HIV and people who were using pre-exposure prophylaxis, or PrEP, to prevent HIV acquisition.) People in the trial had had at least one STI in the previous 12 months.
The people were tested quarterly, and the expectation was that people who didn’t get the antibiotic would have an STI rate of about 10% per quarter. Instead, it was 30%.
People in the doxycycline arm took a median of four doses of the drug over the course of a month, though some took as many as 10, Celum said. They had a median of nine sexual partners apiece.
The proposed CDC guidance would allow advance prescription of the antibiotic to people who met the criteria for the doxycycline PEP. People would be tested for STIs when they began the regimen, and at three to six month intervals after.
Doxycycline is generally well tolerated, though it can cause photosensitivity and irritation of the esophagus. It’s important to drink fluids and not to lie down for 30 minutes after taking the drug.
Some sexual health clinics in San Francisco have been using the regimen since last fall, Celum said. “I think the early data are encouraging in terms of yes, there’s interest, and yes, it’s reaching the right individuals.”
STI rates in the U.S. have soared in recent years, increasing by 42% in the decade from 2011 to 2021. There were 1.6 million cases of chlamydia, 710,000 cases of gonorrhea, 177,000 cases of syphilis, and nearly 2,900 cases of congenital syphilis — syphilis transferred to babies at birth — in 2021, the CDC reported.
While it appears clear there is keen interest in pursuing this strategy, there are concerns that the additional use of doxycycline will fuel antibiotic resistance, and could affect the microbiomes of people on the regimen. Some of the “bystander” pathogens that people carry — for instance Staphylococcus aureus in the nose — could develop resistance to doxycycline and other tetracycline drugs.
“Current data suggest overall benefit of the use of doxycycline PEP, but potential risks related to the development of resistance and impacts on the microbiome will need to be closely monitored after implementation of these guidelines,” the CDC guidance stated.
In addition to possible downsides, there could be more benefits of using this approach, Celum said. Gonorrhea, for instance, has worked its way through nearly all available classes of antibiotics, with only ceftriaxone left as a drug that can cure most cases. But in the DoxyPEP trial, there was a 50% reduction in use of ceftriaxone among the cohort taking doxycycline, potentially helping to preserve how long ceftriaxone will be effective.
There could also be an overall reduction in transmission of STIs, by protecting people who are at high risk of contracting — and spreading — sexually transmitted infections.