Researchers from the University of Washington (UW), the Kenya Medical Research Institute (KEMRI) and the Hennepin Healthcare Research Institute (HHRI) announced to CROI the results of a clinical trial showing that doxycycline taken after sex does not prevent bacterial sexually transmitted infections (STIs) – chlamydia or gonorrhea – in cisgender women. The dPEP Kenya trial was conducted in Kisumu, Kenya to assess the effectiveness of doxycycline post-exposure prophylaxis (PEP) in preventing bacterial STIs. The study results are highly anticipated as this is the first study of doxycycline PEP in cisgender women, following several studies that have shown a high level of protection against STIs with the use of doxycycline in cisgender men and transgender women in France and the United States.
Differences in anatomy, antibiotic resistance, and adherence offer possible explanations for the lack of effectiveness in cisgender women when it worked for cisgender men and transgender women, and the research team is working to understand the potential role of these differences. “Doxycycline PEP didn’t work for cisgender women in Kenya, but the need for STI prevention is growing worldwide,” said Dr. Jenell Stewart, dPEP Kenya Study Director, Infectious Diseases Physician at Hennepin Healthcare and the University of Minnesota.
Biological differences between the vagina/cervix and the rectum may explain why doxycycline did not prevent STIs in cisgender women; however, the approach to STI treatment does not differ by gender. Antibiotic resistance explains why gonorrhea was not prevented, but it does not explain why chlamydia was not prevented. There are no known cases of antibiotic-resistant chlamydia; however, the rate of doxycycline-resistant gonorrhea was very high, including 100% of infections acquired before the start of the study. Self-reported adherence was high but imperfect, and the frequency and timing of doxycycline use among cisgender women participating in the trial is being assessed. All of the participants were also taking HIV PrEP pills (a drug to prevent HIV) daily, and none of the participants contracted HIV in the year they participated in the study.
At a single site in Kisumu, Kenya, the study recruited 449 cisgender women who took daily oral HIV pre-exposure prophylaxis (PrEP) and were randomized to receive doxycycline or standard care. 18% of participants had an STI at study entry and over the course of the study the rate of STIs remained high – an annual incidence of 27%, which is comparable to rates in men with sex with men in high-income countries. During the 12-month follow-up, 109 new STIs were diagnosed, 50 among those using doxycycline PEP versus 59 among those randomized to no doxycycline and no standard treatment. Most, 78%, of newly diagnosed STIs were chlamydia, 35 among those taking doxycycline PEP and 50 among standard care, which was not statistically different. Only one new case of syphilis was diagnosed in this study, consistent with other studies in the region, and therefore the impact of doxycycline PEP on the prevention of syphilis in cisgender women could not be determined. assessed.
The results of the study are deeply disappointing, and we are committed to understanding why doxycycline PEP did not work in this population and also determining next steps to identify prevention tools that will work and can be used by the women.
Teacher. Elizabeth Bukusi, Principal Investigator of the dPEP Kenya trial and Principal Clinical Investigator at the Kenya Institute of Medical Research
Bacterial STIs in women can lead to lasting and serious consequences, including pelvic inflammatory disease, chronic pain, infertility, pregnancy complications, and increased susceptibility to HIV. As the study team continues to investigate the potential role of biological and behavioral differences in explaining why doxycycline PEP did not work, it is clear that cisgender women need primary prevention strategies for STI.
The trial was funded by the National Institutes of Health (R01AI145971, P30AI027757, K23MH124466) and was conducted at the KEMRI Lumumba site in Kisumu, Kenya. The content is the sole responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Hennepin Health Research Institute