Doxycycline Less Effective, Adhered to for STI Prevention in Women


A randomized trial among young Kenya women showed the post-exposure prophylactic was insignificantly more effective in preventing chlamydia, gonorrhea and syphilis—largely due to inadherence.

Doxycycline Less Effective, Adhered to for STI Prevention in Women

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Post-exposure prophylaxis doxycycline hycate 200 mg (doxycycline PEP) was not associated with significantly lower incidence of sexually transmitted infections (STIs) versus standard care among young, cisgender women in Kenya.1

Recent findings from the dPEP Kenya Study Team show that cisgender women aged 18 – 30 years old did not benefit from the tetracycline antibiotic in the prevention of STIs including Chlamydia trachomatis, Neisseria gonorrhoeae and Treponema pallidum—contradicting previous study findings observed among cisgender men and transgender women treated with the post-exposure prophylactic drug.2 What’s more, the investigative team observed lesser adherence to doxycycline PEP among cisgender women after sexual encounters.

The new data stress the continued need for STI-preventive care options that are both efficacious and accepted by women, who are disproportionately affected by STI complications compared to men.1

Investigators led by Jenell Stewart, DO, MPH, of the division of infectious diseases at Hennepin Healthcare Research Institute at University of Minnesota, conducted a randomized, open-label assessment comparing doxycycline PEP with standard care among Kenyan women 18 – 30 years old in the prevention of incident chlamydia, gonorrhea or syphilis infection. Combined, these 3 common STIs currently constitute nearly 400 million infections annually—with standard measures of prevention including abstinence, condom use and screening not helping to curb the increasing rate.

Stewart and colleagues specifically observed doxycycline PEP—taken ≤72 hours following sexual encounter—in women receiving HIV pre-exposure prophylaxis (PrEP) due to the high rate of bacterial STIs observed in such patients as well as the World Health Organization’s (WHO) call for integrated STI prevention and PrEP care.

“Women are disproportionately burdened by STI sequelae, including pelvic inflammatory disease, chronic pain, infertility, ectopic pregnancy, increased risk of HIV acquisition, and pregnancy and fetal complications,” investigators noted. “Doxycycline PEP effectively reduced the incidence of STIs among cisgender men and transgender women in France and the United States.”

The team enrolled women in Kenya from February – October 2020, randomizing them 1:1 to either doxycycline PEP plus standard care (quarterly STI testing and treatment), or just lone standard care. The treatment arm was instructed to take a 200 mg dose within 72 hours of condomless sexual intercourse. Follow-up visits lasted over 12 months, with participants completing behavioral and symptomatic questionnaires at each visit. They additionally provided blood samples for HIV and STIs, and hair samples for objective measure of doxycycline use.

Patients were additionally offered condoms and contraception, as well as PrEP refills, at each visit; doxycycline was discontinued in the case of pregnancy. Participants were prompted to report sexual exposure relative to condom and doxycycline use.

The final analysis included 224 women randomized to doxycycline PEP versus 225 randomized to standard care. Median cohort age was 24.3 years old; 80 participants (17.9%) received a chlamydia, gonorrhea or syphilis diagnosis at baseline. Another 80 women became pregnant during the trial.

A median of 4 doxycycline doses per month were overserved during the trial (IQR, 0 – 8), similar to the median number of sex acts (n = 4 [IQR, 2 – 8). Nearly half of all follow-up visits included a report of >1 sexual partner in the past quarter (45.6%); another 28.9% visits included a report of ≥3 sexual partners.

Doxycycline coverage of ≥80% following condomless sex was reported in 91.1% of quarterly follow-up reports; 23.3% of visits included a report of women not taking doxycycline after their last sexual intercourse. Among the 50 participants in the treatment arm randomly selected for doxycycline concentration evaluations via hair, the antibiotic was detected in 28 (56%) during ≥1 visit. Across all the quarterly visits, doxycycline was detected in 58 of 200 visits (29%).

Indeed, investigators observed 109 incident STIs among all participants. Fifty cases (25.1 per 100 person-years) were observed in the doxycycline PEP group, versus 59 cases (29.0 per 100) in the standard care group. Among all 109 STIs, chlamydia was the most common (n = 85), followed by gonorrhea (n = 31), dual infection of chlamydia and gonorrhea (n = 8), and syphilis (n = 1).

Overall incidence of STIs was only 12% lower among participants receiving doxycycline PEP versus standard care—an insignificant difference in prevention (relative risk, 0.88; 95% CI, 0.60 – 1.29; P = .51).

Stewart and colleagues observed no serious adverse events related to the antibiotic; nausea was reported in 7.2% of follow-up visits. Another 4 instances of social harm were reported by 3 participants who unintentionally disclosed their use of doxycycline PEP use.

“Among women receiving HIV PrEP in Kenya, the incidence of bacterial STIs was not significantly lower with doxycycline PEP than with standard care,” investigators noted. “Objective assessment of hair samples for doxycycline use suggested that doxycycline was not taken during the majority of months, which is discordant with participant-reported use.”

The team noted the low detection of doxycycline in hair analyses would primarily infer the differing results of this latest trial compared to those observed in past trials involving cisgender men and transgender women—bucking against their expectations.

“The current trial was designed to maximize adherence by enrolling women who were already taking a preventive medication (i.e., PrEP), by having an open-label design without a placebo to ensure that participants knew they had received an active medication with a well-established safety profile, and by offering adherence support with weekly text messages and discrete pill carriers,” they wrote. “Participant-reported adherence was moderately high; however, the results of doxycycline testing in hair suggests that 44% of the participants assigned to receive doxycycline PEP may not have taken any doxycycline.”

All the same, Steward and colleagues concluded their findings put stress on the need for more STI-preventive options for cisgender women. An understanding of adherence to preventive medicines needs to complement the biomedical capabilities of against like doxycycline to help turn the tide on the women-disparate impact of STIs.

“Research on doxycycline PEP is needed across a spectrum of populations; the primary focus has been on cisgender men, among whom three trials have been completed and three more are in process; however, no additional trials are in process for cisgender women, who bear the highest global burden of complications from STIs,” they wrote. “Further trials investigating doxycycline PEP among persons who had been assigned a female sex at birth are warranted.”


  1. Stewart J, Oware K, Donnell D, et al. Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women. N Engl J Med. 2023;389(25):2331-2340. doi:10.1056/NEJMoa2304007
  2. Krewson C. Doxycycline effectiveness against STIs. Contemporary OB/GYN. Published online April 14, 2023. Accessed February 27, 2024.
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