Even though doxycycline postexposure prophylaxis (PEP) has been shown to prevent sexually transmitted infections (STIs) among cisgender men and transgender women, a randomized trial in 449 cisgender women yielded negative results, researchers report. “According to hair-sample analysis, the use of doxycycline PEP among those assigned to receive it was low,” authors write for the dPEP Kenya Study Team.
The open-label trial compared doxycycline PEP (doxycycline hyclate 200 mg taken within 72 hours after condomless sex) with standard care among Kenyan women 18 to 30 years of age who were receiving preexposure prophylaxis (PrEP) against HIV. The primary outcome was any incident infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum, and hair samples were collected quarterly for objective assessment of doxycycline use.
“Participants were followed quarterly over 12 months,” write the authors. “A total of 109 incident STIs occurred (50 in the doxycycline-PEP group [25.1 per 100 person-years] and 59 in the standard-care group [29.0 per 100 person-years]), with no significant between-group difference in incidence (relative risk, 0.88; 95% confidence interval [CI], 0.60 to 1.29; P = 0.51). Among the 109 incident STIs, chlamydia accounted for 85 (78.0%) (35 in the doxycycline-PEP group and 50 in the standard-care group; relative risk, 0.73; 95% CI, 0.47 to 1.13). No serious adverse events were considered by the trial investigators to be related to doxycycline, and there were no incident HIV infections. Among 50 randomly selected participants in the doxycycline-PEP group, doxycycline was detected in 58 of 200 hair samples (29.0%). All N. gonorrhoeae–positive isolates were resistant to doxycycline.”
Editorial: “Where does this leave us as we consider the next steps for chemoprevention against STI — specifically, doxycycline PEP — in cisgender women?” an editorialist asks. “Do these latest trial results leave us in yet another situation in which a promising and effective intervention in men who have sex with men ‘just doesn’t work’ in women? In the United States, the incidence of congenital syphilis has reached an all-time high, and increased uptake of oral PrEP has not reached enough women, leaving the incidence of HIV among them unchanged. For chemoprophylaxis against STI, we need to do better in working out the science of drug delivery, the motivation and context for product use, and the background antibiotic susceptibility to inform the design of interventional trials. With women bearing the brunt of the long-term consequences of untreated STI, we owe them no less.”