Proposed Postexposure Prophylaxis for STIs: Doxy-PEP

Jennifer Middleton, MD, MPH
Posted on October 9, 2023

Earlier this year, I wrote about the increase in sexually transmitted infection (STI) rates in the United States, and the Centers for Disease Control and Prevention (CDC) is now proposing a novel way to stem this tide. The CDC is inviting comment on a draft proposal regarding postexposure prophylaxis (PEP) for STIs with doxycycline, known as “doxy-PEP.”

The CDC’s proposal recommends prescribing doxy-PEP within 72 hours of unprotected sex for cisgender men who have sex with men (MSM) and transgender women who have sex with men who have been diagnosed with an STI in the last year; this population is the only one with evidence of benefit from doxy-PEP. The CDC based its recommendation on two studies. The first study’s participants were MSM and transgender women who have sex with men taking preexposure prophylaxis (PrEP) against HIV infection or living with HIV; all participants had been diagnosed with gonorrhea, chlamydia, or syphilis in the prior 12 months. Participants were randomized to either take 200 mg of doxycycline (doxy-PEP) within 72 hours after unprotected sex or receive “standard care” without doxy-PEP. The doxy-PEP group had a lower incidence of gonorrhea, chlamydia, and syphilis compared with the standard care group; “[i]n a secondary analysis of time to first STI, the incidence was lower by 66% with doxy-PEP than with standard care in the PrEP cohort (hazard ratio, 0.34; 95% CI, 0.23 to 0.51) and by 52% in the PLWH cohort (hazard ratio, 0.48; 95% CI, 0.28 to 0.83).” The second study, which has yet to be peer reviewed but was presented at the Conference on Retroviruses and Opportunistic Infections earlier this year, enrolled MSM taking PrEP (no mention of transgender women in the published abstract) with a history of STI in the prior 12 months. The researchers randomized participants to either take doxy-PEP or not, and they also randomized them to receive meningococcal B vaccine or not. (Previous evidence has suggested that the meningococccal B vaccine may prevent gonorrhea in teens and young adults.) They found that

The incidence of a first episode of CT or syphilis was 5.6 and 35.4 per 100 PY in the Doxy PEP and no PEP arms, respectively (aHR: 0.16; 95%CI: 0.08-0.30). The incidence of a first episode of GC was 20.5 and 41.3 per 100 PY in the Doxy PEP and no PEP arms, respectively (aHR: 0.49; 95%CI: 0.32-0.76). The incidence of a first episode of GC was 9.8 and 19.7 per 100 PY in the meningococcal B vaccine and no vaccine arms, respectively (aHR: 0.49; 95%CI: 0.27-0.88).

Although doxy-PEP was well tolerated by participants in both trials, it’s not without risk. Neisseria gonorrheae resistance to doxycycline is already a problem in France, for example, where similar studies of doxy-PEP found it to be ineffective. Using doxy-PEP in those at low risk of an STI could also contribute to antimicrobial resistance. Only a few studies have been performed in cisgender women and transgender men, and the largest study performed in Kenya did not show any benefit to doxy-PEP use (although Kenya also has significant gonorrhea resistance to doxycycline). Doxycycline is also not recommended to be used in pregnancy because of fetal risk, which may also limit the use of doxy-PEP in cisgender women and transgender men.

PrEP and PEP for HIV continue to be underprescribed in the United States; while we wait for the CDC to finalize its recommendation for doxy-PEP, we can work in our offices and practice sites to identify patients who may benefit from these therapies. You can find information about PrEP and PEP for HIV in the AFP By Topics on Sexually Transmitted Infections and HIV/AIDS.