STIs in women remain common despite doxycycline use after sex

Young cisgender women remain susceptible to contracting sexually transmitted infections (STIs) despite the use of doxycycline after sex, as shown in the results of the open-label DPEP Kenya study.

Overall STI incidence, the primary endpoint, was high at a rate of 27 per 100 person-years, according to one of the study authors Dr Jenell Stewart, assistant professor at the University of Minnesota in Minneapolis, Minnesota, US, who spoke to an audience at CROI 2023.

In the intention-to-treat analysis, the incidence of STI events (measured quarterly for 1 year) did not significantly differ between the group of women who took doxycycline as postexposure prophylaxis (PEP) and the group of those who underwent STI screening and treatment alone (standard of care [SOC]; 50 vs 59 participants; relative risk [RR], 0.88, 95 percent confidence interval [CI], 0.60–1.29; p=0.51). [CROI 2023, abstract 121]

The same was true in separate assessments of chlamydia (35 vs 50 participants; RR, 0.73, 95 percent CI, 0.47–1.13; p=0.16) and gonorrhoea (19 vs 12 participants; RR, 1.64, 95 percent CI, 0.78–3.47; p=0.19).

Results were consistent when the 80 participants who got pregnant during the study were excluded from the analysis, with no significant differences in the incidence of all STIs (RR, 0.91, 95 percent CI, 0.62–1.35; p=0.65) and of chlamydia alone (RR, 0.73, 95 percent CI, 0.46–1.15; p=0.18) between the doxycycline and SOC groups.

Subgroup analyses defined by age, contraceptive use, transactional sex, and presence of STI at baseline yielded similar findings.

Weekly SMS surveys, which were conducted to evaluate concomitant doxycycline PEP use with sex, had an overall 81 percent response rate, Stewart noted. “Participants reported taking doxycycline PEP at least as many days as they had had sex that week in 78 percent of weekly SMS surveys.”

There were no serious adverse events related to doxycycline use, [and] there were no incident HIV infections in either study group,” she added.

Where did things go wrong?

The failure of DPEP Kenya to meet its primary endpoint was contradictory to the positive results obtained in similar studies conducted in cisgender men and transgender women presented in the same meeting, Stewart acknowledged. However, she was quick to point out several possible explanations for the null results of DPEP Kenya.

“One interpretation [involves anatomy, such] that doxycycline does not prevent STIs in endocervical tissue” as opposed to STIs in urethral, rectal, and pharyngeal tissues, Stewart explained.

She also mentioned that antimicrobial resistance should be considered. This is because while there are no known cases of resistant chlamydia globally, the high prevalence rate of tetracycline-resistant gonorrhoea in Kenya may have contributed to the null findings.

Finally, Stewart suggested that the self-reported adherence to doxycycline PEP in the study, although high, may have been imperfect.

Since cisgender women bear the highest burden of morbidity and mortality from bacterial STIs—including Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum infections—Stewart highlighted a persistent need for STI prevention interventions.

DPEP Kenya included 449 cisgender women (median age 24 years, 36.7 percent reported engaging in transactional sex at baseline) residing in Kisumu, Kenya. These women were randomly assigned to receive either doxycycline hyclate 200 mg taken within 72 hours of sex or SOC (ie, quarterly screening and STI treatments).

Overall retention was high, with the participants completing 97 percent of all quarterly follow-up visits. STI prevalence was 17.9 percent overall (C trachomatis, 14.1 percent; N gonorrhoeae, 3.8 percent; T pallidum, 0.4 percent). Doxycycline was halted during pregnancy, which accounted for 10 percent of follow-up time.

“We recruited from HIV PrEP clinics to identify people already taking pills for prophylaxis, and no incident HIV infections occurred. The open-label trial design was used so that participants knew they were receiving doxycycline and not a placebo. Participants also received adherence support with weekly text messages and discreet pill carriers,” Stewart said.

“Further work is ongoing to assess the potential roles of biology and/or behaviour to explain our null results,” she shared.