Doxy-PEP for Bacterial STI Prevention: Meeting Patients Where They Are

EBM Focus - Volume 18, Issue 18

Reference: N Engl J Med. 2023 Apr 6;388(14):1296-1306

Practice Point: Doxycycline 200 mg once within 72 hours of condomless sex reduces the incidence of gonorrhea, chlamydia, and syphilis in men who have sex with men (MSM) and transgender women at high risk for STIs.

EBM Pearl: Be mindful of generalizability — how well a study sample represents the population. While doxy-PEP is effective in reducing rates of bacterial STIs in MSM and transgender women at high risk for STIs, it is unknown if doxy-PEP is effective for other populations such as heterosexual men, cisgender women or others at high risk for STIs.

Sexually transmitted infections (STIs) are on the rise in the US and regardless of your comfort level in taking a sexual history, many individuals are having condomless sex with multiple partners. Fortunately, wrappin’ it up may not be the only way to prevent bacterial STIs. In a recent trial published in NEJM, investigators found that doxycycline postexposure prophylaxis (doxy-PEP) reduced the risk of gonorrhea, chlamydia, and syphilis in high-risk individuals by about 60%.

In this open-label trial, researchers enrolled 501 MSM and transgender women with a history of gonorrhea, chlamydia, or syphilis in the past year and grouped them into two cohorts: those (327) taking HIV pre-exposure prophylaxis (PrEP cohort) and those persons (174) living with HIV (PLWH cohort). Researchers randomized the participants 2:1 to receive doxy-PEP or standard care (treating STIs as they’re diagnosed). Those in the doxy-PEP group were instructed to take doxycycline 200 mg once within 24 hours but no later than 72 hours of condomless anogenital, vaginal, or oral sex with a max dose of 200 mg per day. Participants were screened for STIs every 3 months for 1 year. The primary outcome was the incidence of at least one bacterial STI (gonorrhea, chlamydia, or syphilis) each quarter.

The results were striking and similar in both cohorts, with an absolute risk reduction of about 20% with doxy-PEP in both groups. In the PrEP cohort, STIs were diagnosed in 11% at quarterly visits in the doxycycline group vs 32% in the standard-care group. Similarly in the PLWH cohort, STIs were diagnosed in 12% of the doxycycline group vs 31% in the standard-care group . This comes out to an impressive NNT of 5 to prevent 1 additional bacterial STI in 3 months. When the STIs were analyzed separately, doxy-PEP significantly reduced the incidence of gonorrhea, chlamydia, and syphilis in both cohorts. In terms of antibiotic resistance, gonococcal culture data was limited but showed an increase in resistance to tetracycline. Resistance to doxycycline also increased in participants colonized with Staphylococcus aureus.

There are some aspects of this trial which favor the intervention including the fact that it was (by nature) unblinded and was stopped early for benefit. It is also important to remember that the generalizability of this trial is limited and the results only apply to MSM and transgender women who engage in high-risk sexual behavior. We are not so worried about gonococcal resistance to tetracyclines (given we aren’t losing any treatment options with it) but the effect on Staph aureus warrants further study. Despite these issues, the results are still pretty convincing. In the right population, prescribing doxy-PEP to prevent bacterial STIs probably makes sense, and is certainly an important step in dealing with the reality of patients who do not use condoms consistently, or even at all.

For more information, see the topic Primary Care for Men Who Have Sex With Men in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Nicole Jensen, MD, Family Physician at WholeHealth Medical. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School; Katharine DeGeorge, MD, MS, Deputy Editor at DynaMed and Associate Professor of Family Medicine at the University of Virginia; Dan Randall, MD, Deputy Editor at DynaMed; Vincent Lemaitre, PhD, Senior Medical Writer at DynaMed; Elham Razmpoosh, PhD, Postdoctoral fellow at McMaster University; and Sarah Hill, MSc, Associate Editor at DynaMed.