Why doxycycline PEP lacks clinical data for STI prevention in women

Data from a Kenya-based trial earlier this year showed post-exposure prophylaxis doxycycline hycate 200 mg (doxycycline PEP) was not associated with a clinically significantly reduced incidence of sexually transmitted infections (STIs) versus standard care in cisgender women.¹

In fact, the findings from the multinational dPEP Kenya Study Team showed the antibiotic was poorly adhered to among younger, cisgender women who were considered at risk of Chlamydia trachomatis, Neisseria gonorrhoeae or Treponema pallidum infections after sexual encounters. Though the research was novel in its approach to interpret a potential PEP treatment in this underserved population, the investigators concluded further research needs to consider the behaviors, priorities and needs of cisgender women in the prevention of STIs.

In the first segment of an interview with Contemporary OB/GYN, study author Jenell Stewart, DO, MPH, assistant professor of infectious diseases at Hennepin Healthcare, discussed the history of research into doxycycline PEP—one that which has largely catered to a male patient population with promising results. Among the 3 clinical trials considering people assigned male sex at birth, the antibiotic has been associated with up to 80% reduced risks in chlamydia, syphilis and gonorrhea infections.

“Based on enthusiasm from those highly efficacious results coming out of the United States and France, there's a lot of movement to move this into policy and clinical practice, making sure that people who need tools beyond condoms have access to another option to prevent STIs,” Stewart said. “Similar to what we saw with HIV PrEP, initial trials predominantly focused on men. And a lot of the early evidence came from cisgender men. So, cisgender women are being left behind.”

Much of this gender disparity in doxycycline PEP research and outcomes is due to a lack of clinical evidence supporting its use in people who were born women—warranting Stewart and colleagues’ research. What Stewart derives as the key finding from their assessment is that the drug “didn’t fit into the lives of the young women in Kenya.”

“So, as we're watching STIs skyrocket and we're seeing congenital syphilis rise at alarming rates around the world, we're really wanting to make sure that we are working to find solutions beyond just condoms, which work well for some people,” Stewart said. “But clearly, given the rising rates, we need additional tools. And I'm hopeful that doxycycline PEP might be one of those tools.”

Regarding the gender disparity in doxycycline PEP and general STI prophylaxis research,² Stewart pointed to a pair of potential factors: a less discernible trend of sex networks among people born as women, and clinician worry over the effect of drugs like doxycycline on fetuses. Previous STI post-exposure drugs like tetracycline carried a known risk of impacted fetus development.

“Because of that, and because we do not have data on doxycycline, we often withhold doxycycline for people who are pregnant,” Stewart said. “And I think that the more we can understand what those risks actually are, it can inform that conversation a little bit better.”

The issue of uncertain treatment evidence surrounding doxycycline PEP for cisgender women goes both ways: adverse event risk is as well-interpreted as efficacy in preventing STIs. The difference is that clinicians are combating a public health crisis among women without a full armamentarium; something has to give in the way of research.

“That's a hard conversation to have, when we don't actually have a lot of data on what those health risks are for doxycycline,” Stewart said. “But the data are very clear for syphilis. We know that syphilis is very bad for congenital formation, and that can be a devastating outcome. So, in trying to make that decision between doxycycline and syphilis, it's a pretty clear choice, in my opinion, to take the doxycycline and prevent the syphilis.”

References

1. ^{Kunzmann K. Doxycycline Less Effective, Adhered to for STI Prevention in Women. Contemporary OB/GYN. Published February 27, 2024. https://www.contemporaryobgyn.net/view/doxycycline-less-effective-sti-prevention-women}
2. ^{NATIONAL INSTITUTES OF HEALTH. Cisgender Women Excluded in Pivotal STI Prevention Studies. Today’s Clinical Lab. Published December 21, 2023. https://www.clinicallab.com/cisgender-women-excluded-in-pivotal-sti-prevention-studies-27666}