Doxycycline Fails to Protect Women Against STIs

SEATTLE -- Researchers were scratching their heads over findings that doxycycline prophylaxis failed to prevent sexually transmitted infections (STIs) among African cisgender women, unlike its success among men who have sex with men.

In a trial conducted among 449 women in Kenya who were taking daily pre-exposure prophylaxis (PrEP) to prevent HIV infection, 50 of the women randomized to doxycycline around the time of sexual activity became infected with pathogens causing gonorrhoea or chlamydia, as compared with 59 women in the standard-of-care group (RR 0.88, 95% CI 0.60-1.29, P=0.51), reported Jenell Stewart, DO, MPH, of Hennepin Healthcare and the University of Minnesota in Minneapolis.

"None of the women in the study contracted HIV, so we assume they were adherent in taking their PrEP, so we keep asking ourselves, 'Why was doxycycline not effective in preventing other sexual transmitted diseases, such as chlamydia and gonorrhea?'" Stewart told MedPage Today at the annual Conference on Retroviruses and Opportunistic Infections.

The failure comes after several studies that have shown doxycycline prophylaxis markedly reduced rates of STI among men and transgender women who have sex with men, she said.

So what went wrong? Stewart suggested that it might be anatomy: Endocervical tissue may differ from urethral, rectal, and pharyngeal tissues. She also hypothesized that there could be resistance pathogens that muted the effectiveness of doxycycline in the groups tested. And, Stewart noted, doxycycline might have been taken by women in the standard-of-care contingent through clinics outside the study, which would have skewed results.

She also suggested that adherence to doxycycline might have been imperfect.

"We were trying to reduce the use of antibiotics in this study so the cisgender women were taking doxycycline when they were having sexual contact, whereas the PrEP for HIV was daily," she said. "It is pretty clear that doxycycline is not the answer for preventing sexually transmitted infections among this population of cisgender women in Africa."

In the study, Stewart and colleagues randomly assigned 225 non-pregnant women to standard of care (quarterly STI testing and treatment) and another 224 women to 200-mg doxycycline within 72 hours of sexual activity. Women were followed for 12 months during 2020-2022. If a woman became pregnant during the trial, doxycycline therapy was discontinued.

At baseline, the median age of the women was 24 years, and the median duration of HIV PrEP was about 7 months. Two-thirds of the women were single, 69% had prior pregnancies, 61% were using hormonal contraception, and 37% reported transactional sex. About 18% of the women had a sexually transmitted disease at the start of the trial, mostly chlamydia. Quarterly visits were completed by 95% of the women in the prophylaxis cohort and by 98% of the women receiving standard of care.

About 78% of the women said they had used doxycycline in weekly surveys, indicating a sexually active group. There were 80 pregnancies in the study, 44 among women in the doxycycline group and 36 in the standard-of-care group.

No severe adverse reactions were reported by the women taking doxycycline, although four women in the group reported having experienced social harms related to taking the drug.

Overall, STIs were detected in 109 women during the study, including 85 cases of chlamydia, 31 cases of gonorrhoea, and one case of syphilis (eight women had both a chlamydia and gonorrhoea infection). Chlamydia occurred in 35 women in the doxycycline group and 50 women in the standard-of-care group (RR 0.73, 95% CI 0.47-1.13). Gonorrhoea occurred in 19 and 12 women, respectively (RR 1.64, 95% CI 0.78-3.47).

"The burden of sexually transmitted infections on cisgender women is large and growing," Stewart said. "Sexually transmitted infection prevention interventions remain needed."

In commenting on the study, press conference moderator Landon Myer, MD, of the University of Cape Town, South Africa, called it a "hugely important study in an area that requires greater interest."

However, "I don't think the problem is the drug," he told MedPage Today. "I think the reason the trial failed to show a significant difference is probably due to drug resistance or to adherence. We have more work to do to find the answer."

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