Researchers from the University of Washington (UW), Kenya Medical Research Institute (KEMRI), and Hennepin Healthcare Research Institute (HHRI) published results in the New England Journal of Medicine. The results of the study have been highly anticipated, as this is the first study of doxycycline PEP among cisgender women, following multiple studies that showed a high level of STI protection with doxycycline use among cisgender men and transgender women in France and the United States. In February, Dr. Jenell Stewart presented initial results from the dPEP Kenya clinical trial at CROI demonstrating that doxycycline taken after sex does not prevent bacterial sexually transmitted infections (STIs) – chlamydia or gonorrhea – among cisgender women, but the reason for this had not yet been established.
Objective measure of doxycycline detection in hair samples indicate that use of doxycycline was low in this study. “Doxycycline PEP needs to be studied further among people assigned female sex at birth. I am hopeful that it will work for everyone regardless of sex and gender, but in our study many women didn’t take the doxycycline they were given. We need STI prevention that is proven, accessible, and easy to use.” said Dr. Jenell Stewart, the dPEP Kenya Study Director, Infectious Disease Physician at Hennepin Healthcare and University of Minnesota.
In addition to low use of doxycycline, antibiotic resistance offers an explanation for why gonorrhea wasn’t prevented. The rate of doxycycline resistant gonorrhea was very high, including 100% of the infections acquired prior to starting the study. This is much higher than rates in the US and France, currently estimated to be ~20% of cases. There are no known cases of antibiotic resistant chlamydia, and none were detected in this study.
At a single site in Kisumu, Kenya, the study enrolled 449 cisgender women who were taking daily oral HIV pre-exposure prophylaxis (PrEP) and were randomized to receive doxycycline or standard of care. 18% of participants had an STI at the time they entered the study and over the course of the study the rate of STIs remained high – an annual incidence of 27%, which is comparable to rates among men who have sex with men in high income countries. There were 109 new STIs diagnosed, 50 among those using doxycycline PEP compared to 59 among those randomized to no doxycycline and standard of care, during the course of the 12-month follow-up. Most, 78%, of the new STIs diagnosed were chlamydia, 35 among people taking doxycycline PEP and 50 among standard of 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 preventing syphilis among cisgender women could not be evaluated.
“The results from the study are deeply disappointing, and we are committed to understanding why doxycycline PEP wasn’t taken. We are actively working to find ways to support adherence that will work for and can be used by women,” said Prof. Elizabeth Bukusi, a Principal Investigator of the dPEP Kenya Study and Senior Principal Clinical Research Scientist at the Kenya Medical Research Institute and Professor at University of Washington in Departments of Global Health and Ob/Gyn.
Bacterial STIs in women can lead to lasting and severe consequences including pelvic inflammatory disease, chronic pain, infertility, pregnancy complications, and increased susceptibility to HIV. The dPEP Kenya study team continues to understand why use of doxycycline was low and investigate new ways of deliverying doxycycline prophylaxis that are acceptable and effective. Dr. Stewart is working with Dr. Cherie Blair, Assistant Professor of Infectious Diseases at UCLA, and the Adolescent Trials Network to secure funding for a study of doxycycline prophylaxis against STIs in people assigned female sex at birth regardless of gender in the United States.
The dPEP Kenya 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 solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About Hennepin Healthcare Research Institute
Founded in 1952, Hennepin Healthcare Research Institute (HHRI) supports and administers the medical research conducted at HCMC, the acute care research and teaching hospital of the Hennepin Healthcare System. HHRI supports the work of more than 250 researchers and staff, including MDs, MD/PhDs, PhDs, and PharmDs, and consistently ranks in the top 10 percent of all institutions receiving research funds from the National Institutes of Health. For more information about research at HHRI, visit www.hhrinstitute.org or Twitter @hhrinstitute.
About the International Clinical Research Center
The International Clinical Research Center (ICRC) was established in September 2007 to provide the essential framework and coordination to streamline the implementation of multi-center international infectious disease prevention trials. The ICRC is within the University of Washington, Department of Global Health. The mission of the ICRC is to expand clinical research trial capacity for infectious disease interventions of public health importance. The ICRC facilitates collaborations, improves observational cohort studies and clinical trial operations; and provides repositories of biologic specimens and reagents for future scientific investigations for pathogenesis and prevention research related to HIV and other infectious diseases. For more information, visit http://depts.washington.edu/uwicrc/.
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