Doxycycline postexposure prophylaxis (PEP) up to 72 hours after unprotected sex did not prevent sexually transmitted infections (STIs) in cisgender women, possibly due to poor adherence, a randomized open-label trial showed.
In the study of Kenyan women ages 18 to 30, incident STIs occurred in 50 women taking doxycycline PEP (25.1 per 100 person-years) and 59 who received standard care (29.0 per 100 person-years), with no significant between-group difference in incidence (relative risk [RR] 0.88, 95% CI 0.60-1.29, P=0.51), reported Jenell Stewart, DO, MPH, of the Hennepin Healthcare Research Institute and University of Minnesota in Minneapolis, and colleagues.
However, hair sample analysis suggested that 44% of women assigned to doxycycline PEP may have never took the drug, the authors noted in the New England Journal of Medicine.
“It is important to understand why so many didn’t use it,” Stewart told MedPage Today in an email.
Stewart first presented the trial results at this year’s Conference on Retroviruses and Opportunistic Infections (CROI). At that time, researchers puzzled over why doxycycline PEP failed to prevent STIs, given that previous trials showed that the treatment prevented STIs in cisgender men and transgender women.
“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?” wrote Jeanne Marrazzo, MD, MPH, director of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, in an accompanying editorial.
Stewart said that “the key takeaway is that we still don’t know if doxycycline PEP will be a prevention strategy that works well for people assigned female sex at birth. It is important for innovative biomedical strategies to be studied in everyone and not solely focus on men who have sex with men.”
The CDC recently proposed guidelines for using doxycycline PEP to prevent chlamydia, gonorrhea, and syphilis in men who have sex with men and transgender women.
“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,” Marrazzo wrote. “With women bearing the brunt of the long-term consequences of untreated STI, we owe them no less.”
When designing the trial, Stewart and team wanted to maximize adherence by enrolling women who were already taking pre-exposure prophylaxis (PrEP) to prevent HIV infection. However, they noted that some key factors could have contributed to the negative outcomes of this trial when compared with the previous trials enrolling men who have sex with men and transgender women.
For example, number of partners, frequency of sexual exposures, and the availability of testing and treatment services for partners could influence results. Additionally, site of infection may have played a role. Cisgender women are more likely to have endocervical infections rather than rectal or pharyngeal infections, where doxycycline concentrations may be higher.
The current study included 449 women (median age 24), and compared doxycycline PEP 200 mg taken within 72 hours after condomless sex versus standard care defined as quarterly STI testing and treatment alone. All participants were receiving daily HIV PrEP.
The primary endpoint was new infection with Chlamydia trachomatis, Neisseria gonorrhoeae, or Treponema pallidum. Participants were followed quarterly for a period of 12 months. The median number of sexual exposures was four per month, and the median number of doxycycline doses was four per month (IQR 2-8). Hair analysis in women assigned to receive doxycycline revealed that only 29% of samples contained the drug, but 56% of participants had doxycycline detected in their hair samples in at least one quarterly follow-up visit.
Chlamydia accounted for 78% of incident STIs, and occurred in 35 women in the doxycycline PEP group versus 50 in the standard-care group (RR 0.73, 95% CI 0.47-1.13). There were 19 cases of gonorrhea in those receiving doxycycline PEP versus 12 in the standard-care group (RR 1.64, 95% CI 0.78-3.47). All cases of gonorrhea were tetracycline-resistant.
The most commonly reported side effects in the doxycycline group were nausea and vomiting. No serious adverse events were related to doxycycline.
Disclosures
The study was supported by grants from the National Institutes of Health.
Stewart disclosed no relationships with industry. Several co-authors reported ties to industry.
Marrazzo disclosed no relationships with industry.
Primary Source
New England Journal of Medicine
Source Reference: Stewart J, et al “Doxycycline prophylaxis to prevent sexually transmitted infections in women” N Engl J Med 2023; DOI: 10.1056/NEJMoa2304007.
Secondary Source
New England Journal of Medicine
Source Reference: Marrazzo J “Doxycycline postexposure prophylaxis for STIs in women — uncertain benefit, urgent need” N Engl J Med 2023; DOI: 10.1056/NEJMe2311948.
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