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August 23, 2023

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Preventing Bacterial Sexually Transmitted Infections With Postexposure Doxycycline

By Lauren Richey, MD, MPH, FIDSA

Rates of sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women are increasing, and new interventions are necessary. Doxycycline is a safe, inexpensive, generic medication that is effective against syphilis and chlamydia. This study, called DoxyPEP, was designed to assess the effectiveness of doxycycline in the prevention of STIs. 

This randomized, open-label study included MSM and transgender women with HIV or on pre-exposure prophylaxis (PrEP) for HIV. It recruited from 2 STI clinics and 2 HIV clinics in Seattle and San Francisco. Inclusion criteria was age over 18, assigned male sex at birth, HIV positive status or being on PrEP, a history of condomless anal or oral sex in the past 12 months, and a diagnosis of syphilis, gonorrhea, or chlamydia in the past 12 months. Participants were randomized 2:1 to DoxyPEP treatment or standard care, respectively. Participants in the DoxyPEP group were given doxycycline and told to take 200 mg of doxycycline within 24 hours of (but no more than 72 hours after) any condomless sex act. The maximum dose was 200 mg per 24 hours. Participants were followed for a year with quarterly visits. The primary end point was the incidence of an STI per follow-up quarter. 

There were 501 participants: 327 in the PrEP cohort and 174 in the cohort of people with HIV (PWH). In the PrEP cohort, an STI was diagnosed in 10.7% of the quarters in the DoxyPEP group and 31.9% in the standard of care group (relative risk, 0.34; P < .001). In the PWH cohort, an STI was diagnosed in 11.8% of the quarters in the DoxyPEP group and 30.5% in the standard of care group (RR, 0.38; P < .001). There was a reduction in chlamydia, syphilis, and gonorrhea when analyzed separately among the two groups. That reduction was significant for each, except that the reduction in syphilis was not significant in the PWH group. Five grade-three adverse events occurred, and there were no serious adverse events. Only a small number had gonorrhea cultures; among those, 5 out of 13 in the doxycycline group and 2 out of 16 in the standard of care group had tetracycline resistance. 

DoxyPEP taken within 72 hours of condomless sex decreased gonorrhea, chlamydia, and syphilis by two thirds among MSM and transgender women who had an STI in the past year. 

(Luetkemeyer et al. N Engl J Med. 2023;388:1296-306.)

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