Post-exposure doxycycline prevents STIs in MSM, TGW with HIV or on PrEP

Doxycycline, taken with 72 hours of unprotected sex, could prevent sexually transmitted infections (STIs) in men who have sex with men (MSM) or transgender women (TGW) who are either living with HIV (PLHIV) or are receiving pre-exposure prophylaxis (PrEP), according to a study presented at AIDS 2022.

“Doxycycline post-exposure prophylaxis [PEP] taken within 72 hours of condomless sex substantially reduced the incidence of bacterial STIs, with a quarterly reduction of 62 percent in PLHIV and 66 percent in those taking PrEP,” commented study author Professor Annie Luetkemeyer from the Zuckerberg San Francisco General Hospital, University of California, San Francisco (UCSF), San Francisco, California, US.

The population of the open-label DoxyPEP trial comprised 501 MSM and TGW from Seattle, Washington, and San Francisco, California, US (median age 38 years, 67 percent White), who were either living with HIV or on PrEP. To be included, they needed to have tested positive for early syphilis, Neisseria gonorrhoeae (N. gonorrhoeae), or Chlamydia trachomatis (C. trachomatis) in the previous year. They were randomized 2:1 to receive doxycycline hyclate (200 mg) or no doxycycline (standard of care only; control group) administered within 72 hours of condomless sex. The participants were followed up for 12 months. Testing for STI was carried out at enrolment, quarterly, or if symptoms arose.

A total of 327 participants were on PrEP (median age 36 years) and 174 were PLHIV (median age 43 years). Four percent identified as TGW or gender diverse. Participants had a median nine sex partners in the past 3 months. The most common STI experienced by the participants in the previous year was N. gonorrhoeae (69 percent), followed by C. trachomatis and syphilis (58 and 20 percent, respectively).

Among those on PrEP, there was a 66 percent significant reduction each quarter year in the incidence of new STIs among participants who received doxycycline compared with the control group (10.7 percent vs 31.9 percent; risk reduction [RR], 0.34, 95 percent confidence interval [CI], 0.24–0.46; p<0.0001). [AIDS 2022, abstract OALBX0103]

STI incidence was also significantly reduced by 62 percent among participants with HIV who did vs did not receive doxycycline (11.8 percent vs 30.5 percent; RR, 0.38, 95 percent CI, 0.24–0.60; p<0.0001).

Overall incidence of STIs was reduced each quarter with vs without doxycycline (RR, 0.35, 95 percent CI, 0.27–0.46; p<0.0001). In the PrEP cohort, quarterly incidence of gonorrhoea was 9.1 percent vs 20.2 percent in the doxycycline vs control group (RR, 0.45; p<0.0001), chlamydia incidence 1.4 percent vs 12.1 percent (RR, 0.12; p<0.0001), and syphilis incidence 0.4 percent vs 2.7 percent (RR, 0.13; p=0.0084). In the PLHIV cohort, gonorrhoea, chlamydia, and syphilis incidence in the doxycycline vs control group was 8.9 percent vs 20.3 percent (RR, 0.43; p=0.001), 3.9 percent vs 14.8 percent (RR, 0.26; p=0.0007), and 0.7 percent vs 2.3 percent (RR, 0.23; p=0.095), respectively.

Most STIs were asymptomatic. Participants who were on doxycycline tended to have fewer symptomatic STIs at diagnosis than those in the control group, in both the PrEP (15 percent vs 28 percent) and PLHIV cohorts (17 percent vs 24 percent).

Doxycycline PEP was safe, acceptable, and had high adherence rates, with 1.5 percent discontinuing treatment due to intolerance or preference, said Luetkemeyer. There were no reports of grade ≥3 adverse events (AEs), serious AEs, or grade ≥2 lab abnormalities.

Following a scheduled interim analysis in May 2022, the data and safety monitoring board recommended cessation of enrolment due to significant effectiveness of the intervention in both cohorts. They also recommended continued doxycycline treatment in the control group. 

Practice-changing results?

“There is a global epidemic of STIs [which] disproportionately impacts MSM and TGW, particularly those who are living with HIV or who are taking HIV PrEP,” said Luetkemeyer.

“Based on this data, we think that doxycycline PEP has the potential as an effective prevention strategy in populations with high STI incidence,” she concluded.

She highlighted the need for larger studies and ongoing surveillance in doxycycline PEP users to identify the impact of the treatment on tetracycline resistance in gonorrhoea.

“DoxyPEP represents an important advance in reducing STIs within two vulnerable populations – MSM and TGW,” commented Professor Sharon Lewin, IAS President-Elect and Director of The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia, who was not affiliated with the trial. “I look forward to learning more about the implementation of this prevention measure and any long-term effects of using antibiotics for STI prevention,” she said.