Doxy-PEP: What Do We Know?

Doxycycline is not new. In fact, this medication has been in use since the 1960s for treatment against infections caused by bacteria and other parasites. Doxycycline is a broad-spectrum antibiotic from the tetracycline class that fights different types of bacteria, allowing it to be used when treatment must be initiated prior to obtaining test results or when the specific bacteria causing an infection is unknown. Aside from bacterial STIs, doxycycline is used to treat infections of the eyes, respiratory system, urinary tract, and skin (NIH Office of AIDS Research, 2025).

The drug comes in different strengths or dosages, including 100 mg capsules or tablets. For STI prevention, the recommended dose is 200 mg taken within 24 to 72 hours of condomless oral, vaginal, or anal sex. Taking it within 24 hours after sex is the ideal. Depending on sexual activity, doxycycline may be taken daily but the maximum dose is 200 mg every 24 hours. Doxy-PEP is safe to take with either oral or injectable HIV preexposure prophylaxis (PrEP) medication (Los Angeles County Department of Public Health (LAC DPH), 2024a). People who want to start Doxy-PEP should consult a doctor to discuss potential side effects and interactions with other medications.

Ideally, doctors and medical providers should offer Doxy-PEP as part of a comprehensive sexual health assessment, along with appropriate HIV and STI screening, treatment, and linkage to care and related services. To be prescribed Doxy-PEP, persons undergo an initial visit with their doctor to be tested or screened for gonorrhea, chlamydia, and syphilis. People who are HIV-negative or whose status is unknown should also consider HIV testing and HIV PrEP at that time. Other assessments during the initial visit may include a complete blood count and liver and renal function tests to determine baseline levels, and patients should inform their doctor if they have kidney or liver disease (LAC DPH, 2024a). Doxycycline is not advised for pregnant women, so pregnancy must first be ruled out before they are prescribed the drug (Nguyen et al, 2025).

Every three to four months, there should be follow-up visits to retest for STIs and to consider HIV PrEP or receive HIV treatment, as appropriate. If syphilis is suspected, presumptive treatment of syphilis is also recommended (LAC DPH, 2024a). The Centers for Disease Control and Prevention (CDC) adds that a person’s continuing need for Doxy-PEP should be assessed during these follow-up visits. Their recommendation of follow-up visits every three to six months after the initial Doxy-PEP prescription differs slightly from the frequency suggested by LAC DPH (CDC, 2025).

Federal
Initially, local public health agencies led the way on the use of doxycycline for STI prevention (see below); however, national guidelines from the CDC for Doxy-PEP were released in June 2024. The CDC deems that high-quality evidence exists to offer Doxy-PEP to gay, bisexual, and other men who have sex with men, as well as transgender women, who have had at least one bacterial STI in the past twelve months and counsel them about its risks and benefits. Citing insufficient evidence, the CDC currently gives no recommendation on the use of Doxy-PEP among cisgender women, transgender men, other queer and nonbinary persons, or cisgender straight men.

California
Additionally, the California Department of Public Health (CDPH) advises providers to offer Doxy-PEP, using shared patient-provider decision making, both to individuals who are not pregnant that are at higher risk for bacterial STIs and to people who request it, even if they have no previous STI diagnosis or have not disclosed their risk exposure (CDPH, 2023).

Los Angeles
The Los Angeles County Department of Public Health recommends that medical providers prescribe Doxy-PEP to both transgender women and gay, bisexual, and other men who have sex with men who have had one bacterial STI in the past twelve months (LAC DPH. 2024b). LAC DPH also recommends Doxy-PEP to individuals who have frequent condomless sex with multiple partners who may be at higher risk for an STI (LAC DPH,2024a).

San Francisco
It should be noted that health jurisdictions vary regarding their recommended eligibility guidelines for Doxy-PEP. San Francisco was one of two sites of the US DoxyPEP clinical trial and its Department of Public Health (SFDPH) was first in the nation to issue Doxy-PEP guidance as a public health authority (October 20, 2022).
SFDPH initially recommended Doxy-PEP to cisgender men and transgender women who had a bacterial STI and had engaged in condomless anal or oral sex in the past year with partners assigned male at birth (SFDPH,2022).

However, updated guidelines issued in September 2024 now recommend Doxy-PEP not only for cisgender men and transgender women but also for other gender-diverse people assigned male at birth who have had a bacterial STI and had condomless sex with one or more partners assigned male at birth. The latest guidelines also advise providers to discuss and offer Doxy-PEP to cisgender men, transgender women, and genderdiverse people, irrespective of sex at birth, who did not have an STI in the past year but had condomless sex with two or more sexual partners (SFDPH, 2024).

Elsewhere
Similar to the above California counties, other urban public health departments, such as those of New York City and Seattle, recommend Doxy-PEP to MSM and transgender women with a history of STIs in the previous year—and in Seattle, to non-binary people assigned male at birth with the same history and have condomless sex with same-sex partners. In these two cities, providers are further advised to consider prescribing episodic Doxy-PEP to patients anticipating periods of greater sexual activity, for example, when attending group sex events, or in such circumstances as sex outside one’s usual sexual networks or with new or anonymous partners or when trading sex (NYC Health Department, 2023). Interestingly, in its latest January 2025 guidelines, the local health authority of Seattle, the other site of the DoxyPEP trial, tells providers to consider offering it to persons assigned female at birth of any gender identity who are at particularly high risk for syphilis or living homeless (PHSKC, 2025).

Both randomized trials and real-world studies have shown the potential of Doxy-PEP for reducing STI incidence (Luetkemeyer et al., 2023; Molina et al., 2024; Molina et al., 2018; Osmundson et al., 2025). In the United States, STI cases overall decreased 1.8% from 2022 to 2023, with gonorrhea declining 7.2%. Chlamydia cases, however, remained largely stable and total syphilis increased by 1%. California, over the same period, reported reductions of 1.2%, 7.6%, and 2.4% in cases of chlamydia, gonorrhea, and syphilis respectively (CDPH,2024). Young adults, MSM, and Black persons in the United States continue to bear a larger share of the STI burden relative to their share in the population (CDC, 2024). Thus, while advances in vaccine and antibiotic development remain slow (Marrazzo and Dionne, 2025), Doxy-PEP is a welcome addition to the public health toolbox. Extending it to more individuals within communities for whom it is recommended deserves close consideration.