The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.
"This was the first trial to evaluate doxycycline PEP for cisgender women," said first author Jenell Stewart, DO, of the University of Minnesota, in Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses and Opportunistic Infections (CROI) 2023 Annual Meeting.
"Unfortunately, our primary outcome was not statistically significant — we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women," she said.
The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.
The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).
Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.
In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.
Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk 0.88; P = .51).
Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; eight had both infections, and there was one syphilis infection.
The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex and STI at baseline.
None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
Cisgender Women Bear "Highest Burden" of STIs
The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention (CDC) reporting that women also disproportionately bear the long-term consequences of STIs.
"For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the US, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated," the CDC reports.
The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Stewart said.
Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
Adherence, Anatomy, Resistance
The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Stewart.
In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.
Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.
The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.
The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%
Of note, women reported the use of the treatment to be "imperfect," suggesting social problems, such as biases toward the use of the prophylaxis.
The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Stewart said.
"The burden of STIs on cisgender women is large and growing," she concluded. "STI prevention interventions are needed."
Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings "are somewhat surprising because results from trials in other populations have been positive.
"But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue," Heffron, a professor at the Department of Medicine, Heersink School of Medicine, and director of the Center for AIDS Research at the University of Alabama Birmingham, told Medscape Medical News.
Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.
"For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy," Heffron said.
"We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy."
The authors and Heffron have disclosed no relevant financial relationships.
Conference on Retroviruses and Opportunistic Infections (CROI) 2023 Annual Meeting: Abstract 121. Presented February 20, 2022.
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Cite this: Doxy PEP Does Not Lower Risk of STIs in Cisgender Women - Medscape - Feb 23, 2023.