HIV Meds Update: DoxyPEP – Doxycycline for STI Prevention

The DoxyPEP Study evaluated the efficacy of doxycycline taken as post-exposure prophylaxis (PEP) on incidence of bacterial sexually transmitted infections (STIs), chlamydia (CT), gonorrhea (GC), and syphilis, in men who have sex with men (MSM) and transgender women (TGW).1 It was based on the earlier findings of a small sub study nested within the IPERGAY oral PrEP study in MSM.2

This randomized, open-label trial was conducted at STI and HIV clinics in San Francisco and Seattle. It studied 2 cohorts – MSM/TGW with HIV (n=174) and HIV-uninfected MSM/TGW on PrEP (n=327); participants were at high risk of STIs (condomless sex with one or more partners in the past year and at least 1 STI in the past year [at baseline, subjects reported a median of 9 partners in the previous 3 months]). The median age of subjects was 38; 96% were male, and 4% were TGW/gender diverse. Subjects were randomized 2:1 to receive doxy-PEP or no PEP. The doxy-PEP subjects were instructed to take oral doxycycline 200 mg within 72 hours after condomless sex (oral and/or anal). STI testing was done every 3 months.

In follow-up, PEP subjects reported a median of 7.3 sex acts per month, with doxycycline taken for 87% of these. Substantial decreases in incident bacterial STIs were seen in the doxy-PEP groups compared with the control groups -- a reduction of 65% overall per quarter (62% in the PWH cohort and 66% in the PrEP cohort). This finding was true for all three bacterial STIs:

Risk Reduction per Quarter (Doxy-PEP vs Control arm)

Cohort ChlamydiaGonorrheaSyphilis
HIV cohort74%57%77%
PrEP cohort88%55%87%
STI Incidence Reduction

Differences between the doxy-PEP and control arms were statistically significant, except for syphilis incidence in PWH (where the numbers of cases were very low in both arms). For CT and GC, doxy-PEP reduced infections at oral, urethral, and anal sites.

Investigators reported no significant adverse effects (AEs) attributable to doxycycline; 1.5% of participants discontinued the study because of AEs or other issues. There was no signal of concern about emergent GC resistance to doxycycline in study participants, though researchers acknowledge that more research will be needed on the possible impact of doxy-PEP on bacterial resistance.

 The DoxyPEP study was stopped early (in May 2022) by the Data and Safety Monitoring Board (DSMB) after an interim analysis demonstrated efficacy.

Clinical bottom line

This study found that use of doxy-PEP very substantially reduced bacterial STIs in MSM and TGW, regardless of HIV status. These findings are practice-changing, and many clinics and jurisdictions have worked quickly to develop guidelines and protocols for implementation of doxy-PEP in high risk MSM and TGW. For example, see provider and patient materials prepared by the San Francisco Department of Public Health.

The CDC has issued a permissive “response” to the DoxyPEP data presented to date, and states that clinical guidance will be forthcoming.  Doxy-PEP has not been shown to prevent bacterial STIs in the setting of vaginal receptive sex and is not currently recommended for cisgender women. A study in cisgender women in Kenya was recently reported at CROI 2023: it showed no protective effect.3


  1. Luetkemeyer A, Dombrowski J, Cohen S, et al. Doxycycline post-exposure prophylaxis for STI prevention among MSM and transgender women on HIV PrEP or living with HIV: high efficacy to reduce incident STI’s in a randomized trial. AIDS 2022, July 29-August 2, 2022, Montreal.  Abstract OALBX0103.
  2. Molina J-M, Charreau I, Chidiac C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial.Lancet Infect Dis.  2018 Mar;18(3):308-317.
  3. Stewart J, Oware K, Donnell D, et al. Doxycycline postexposure prophylaxis for prevention of STIs among cisgender women. 30th Conference on Retroviruses and Opportunistic Infections, February 19-22, 2023. Seattle, Washington. Abstract 121.
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