According to the U.S. Centers for Disease Control and Prevention (CDC), bacterial sexually transmitted infections (STIs) remain a significant public health concern. In 2021, 1.64 million cases of chlamydia, 710,151 cases of gonorrhea, and 176,713 cases of syphilis were reported (Centers for Disease Control and Prevention [CDC], 2023e). Bacterial STIs can be treated and cured with antibiotics, (World Health Organization [WHO], 2023) however, untreated STIs can have long-term consequences. Untreated syphilis can damage the heart and nervous system, lead to hearing loss, blindness, stroke, and death (Centers for Disease Control and Prevention [CDC], 2023g). Additionally, active syphilis, chlamydia or gonorrhea increases vulnerability to acquiring HIV (Centers for Disease Control and Prevention [CDC], 2023g; Centers for Disease Control and Prevention [CDC], 2023b, Centers for Disease Control and Prevention [CDC], 2023a).

Gay and bisexual men and other men who have sex with men (GBMSM) experience disproportionately high rates of sexually transmitted infections (Centers for Disease Control and Prevention [CDC], 2023c). In 2021, GBMSM accounted for nearly half of primary and secondary syphilis cases, and nearly one third of gonorrhea cases—while representing only 4% of the U.S. population (Centers for Disease Control and Prevention [CDC], 2023f). Individual factors such as improper condom use, along with structural and community factors such as lack of access to regular medical care, discrimination and stigma play a contributing role in the higher rates of STIs among GBMSM (Centers for Disease Control and Prevention [CDC], 2023c).

Doxycycline post-exposure prophylaxis (Doxy-PEP) is a STI-prevention strategy that involves taking 200 mg doxycycline within 24 hours (and no more than 72 hours) after condomless oral, anal, or vaginal sex (Luetkemeyer et al., 2023). This strategy significantly reduces the risk of acquiring bacterial STIs (Luetkemeyer et al., 2023). In a randomized controlled trial involving MSM and transgender women, participants on Doxy-PEP saw a reduction in syphilis by 87%, chlamydia by 88%, and gonorrhea by 55% for individuals taking HIV pre-exposure prophylaxis (HIV-PrEP). Among individuals living with HIV, Doxy-PEP reduced syphilis by 77%, chlamydia by 74%, and gonorrhea by 57% (Luetkemeyer et al., 2023). Doxycycline is an Food and Drug Administration approved (FDA) broad-spectrum antibiotic that has been available on the market since the early 1960s (National Academies of Sciences, Engineering, and Medicine et al., 2020). Doxycycline has been used for decades because of its safety profile, low-cost, mild potential side-effects, and limited drug-to-drug interaction (Luetkemeyer et al., 2023; Howard Brown Health, 2023). Doxycycline is also the recommended treatment regimen for chlamydia and a supplemental regimen for syphilis (Workowski, 2021). Doxy-PEP as a STI-prevention strategy is not currently FDA-approved.

On October 2, 2023, the CDC released draft guidelines for Doxy-PEP (Centers for Disease Control and Prevention [CDC], 2023d). Meanwhile, several clinics throughout the U.S. have already begun prescribing Doxy-PEP as an STI-prevention strategy including the San Francisco AIDS Foundation (San Francisco AIDS Foundation [SFAF], 2023) and Howard Brown Health Howard Brown Health (2023). Clinics have begun prescribing Doxy-PEP despite it being an off-label use of doxycycline in light of successful clinical findings and the pressing need for STI-prevention methods. Several departments of health have released guidelines for the use of Doxy-PEP (San Francisco Department of Public Health, 2023; California Department of Public Health, 2023; New Mexico Department of Health, 2023; New York City Department of Health and Mental Hygiene, 2023.). The National Coalition of STD Directors (NCSD) has also released a Doxy-PEP implementation toolkit (National Coalition of STD Directors [NCSD], 2023). The emergence of Doxy-PEP guidelines across departments of health indicates a promising trajectory of support for this prevention strategy among providers and public health policy-makers. Doxy-PEP has the potential to play an important role in addressing the ongoing STI epidemic in the U.S.

Although there are promising data on Doxy-PEP’s efficacy as an STI-prevention strategy, there have been few studies evaluating its acceptability among key populations like GBMSM. One exception includes an online survey study, which was launched across gay geosocial-networking applications in six U.S. cities. This study indicated that 84% of the users of this app were interested in using Doxy-PEP (Spinelli et al., 2019). Notably, one qualitative study conducted in Sydney, Australia, assessed the perceptions of “STI pre-exposure prophylaxis” among GBM vulnerable to STIs, which found that participants were “cautiously optimistic” about STI-PrEP, and for many the perceived benefits outweighed the perceived risks (Horn et al., 2020). Our study lends a qualitative lens to the literature on Doxy-PEP by assessing GBMSM’s perceptions regarding Doxy-PEP in the U.S., and their interest in using this novel STI-prevention strategy.