NIH Study: Doxycycline Reduces STI Incidence by Two-Thirds

The oral antibiotic, doxycycline, prevented the acquisition of sexually transmitted infections (STIs) when tested among men who have sex with men (MSM) and transgender women who took the medication within 72 hours of having condomless sex, according to findings published today in The New England Journal of Medicine. Specifically, the post-exposure approach, termed doxy-PEP, resulted in a two-thirds reduction in the incidence of syphilis, gonorrhea, and chlamydia among the study participants, all of whom reported having an STI within the previous year. 

However, the research also revealed a slight increase in antibacterial resistance that requires further exploration per the authors. The research was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

“Effective methods for preventing sexually transmitted infections are badly needed,” said Hugh Auchincloss, MD, NIAID acting director. “This is an encouraging finding that could help reduce the number of sexually transmitted infections in populations most at risk.”

STI incidence has been increasing in the United States over the past few years with a disproportionate impact among MSM and transgender women. An estimated 2.5 million cases of syphilis, gonorrhea, and chlamydia occurred in 2021 up from 2.4 million cases in 2020, according to the Centers for Disease Control and Prevention. If left untreated, STIs can lead to serious health consequences, including brain and nerve problems, blindness, infertility, and an increased risk of HIV infection. Antimicrobial resistance among STIs is an emerging public health threat, particularly with Neisseria gonorrhoeae, and threatens available treatment options.

UCSF study with doxycycline

The study was led by researchers at the University of California at San Francisco (UCSF) and the University of Washington, Seattle, WA. It enrolled 501 adults at four clinic sites in San Francisco and Seattle who were at least 18 years of age; assigned male sex at birth; reported sexual activity with a man in the previous year; diagnosed with HIV or taking or planning to take pre-exposure prophylaxis (PrEP) medication to prevent HIV acquisition; and diagnosed with gonorrhea, chlamydia or early syphilis in the prior year. Of those enrolled, 327 participants were taking HIV PrEP medications, and 174 participants were people living with HIV.

Participants were randomly assigned to receive either doxy-PEP or standard-of-care. Those in the doxy-PEP arm were instructed to take one 200 mg doxycycline (delayed release) tablet, ideally within 24 hours but no later than 72 hours after condomless sex. 

Doxycycline is a broad-spectrum antibiotic in a family called tetracyclines. Participants were assessed by study staff every three months for adherence and side effects to the medication regimen and tested for STIs. Participant acceptability of the medication was assessed at six- and 12-month clinic visits. An independent data and safety monitoring board reviewed the study progress and safety and effectiveness data every six months.

Among participants on HIV PrEP, at least one or more STIs were diagnosed in 10.7 percent of quarterly clinic visits in the doxy-PEP study arm compared to 31.9 percent of visits in the standard-of-care arm. Among study participants living with HIV, one or more STIs were diagnosed in 11.8 percent of quarterly visits in the doxy-PEP arm versus 30.5 percent in the standard-of-care arm. 

Gonorrhea was the most frequently diagnosed STI in the study. Participants reported good adherence to the medication regimen with 86.2 percent reporting taking doxy-PEP consistently within 72 hours of condomless sex, and 71.3 percent reporting never missing a dose. No safety or acceptability issues were identified in the study.

“Given its demonstrated efficacy in several trials, doxy-PEP should be considered as part of a sexual health package for men who have sex with men and transwomen if they have an increased risk of STIs,” according to Annie Luetkemeyer, MD, professor of infectious diseases at Zuckerberg San Francisco General Hospital at UCSF, and co-principal investigator of the study. “It will be important to monitor the impact of doxy-PEP on antimicrobial resistance patterns over time and weigh this against the demonstrated benefit of reduced STIs and associated decreased antibiotic use for STI treatment in men at elevated risk for recurrent STIs.”

The antibiotic potential of doxy-PEP 

In examining the potential for antimicrobial resistance during doxy-PEP use, the researchers discovered tetracycline resistance in a greater number of incident gonorrhea strains among those in the doxy-PEP arm than among those in the standard of care group (38.5 percent versus 12.5 percent, respectively). This suggests that doxy-PEP may offer less protection against gonorrhea strains that are already tetracycline-resistant and that wider population-based surveillance for this type of resistance is important. 

Additionally, the researchers found that doxy-PEP reduced Staphylococcus aureus by 50 percent after a year. However, in those who still had Staphylococcus aureus colonization at month-12, a modestly higher proportion of those in the doxy-PEP group had doxycycline resistance (16 percent vs 8 percent). 

This is important because doxycycline may be used to treat methicillin-resistant Staphylococcus aureus skin and soft tissue infections. Additional research and longer follow-up periods are needed to examine the potential antimicrobial resistance effect of intermittent doxy-PEP use. Doxy-PEP use in other populations disproportionately impacted by STIs, including women with HIV and those taking HIV PrEP, deserves further exploration as well.

“We need new, effective STI prevention methods and three studies have now demonstrated that doxy-PEP significantly reduces gonorrhea, chlamydia, and syphilis. In the next several years during the implementation of doxy-PEP, we need to learn about maximizing equitable access and impact,” said Connie Celum, MD, MPH, professor of global health and medicine at the University of Washington and co-principal investigator of the DoxyPEP study.

- This press release was originally published on the National Institutes of Health website