Incidence of sexually transmitted infections (STIs) at a local southern US clinic fell by 67% after initiation of doxycycline post-exposure prophylaxis (DoxyPEP) prescribing without any changes to STI testing patterns, according to research presented on August 24 at the annual meeting of AIDS 2026 in Rio de Janeiro.

“Taken together, these findings suggest that the benefits of DoxyPEP observed in clinical trials translate well to routine HIV and PrEP care in the southern United States, even among patients with more diverse risk profiles and under real-world conditions,” Emily D. Niehaus, MD, MPH, an infectious diseases specialist at Duke University in Durham, North Carolina, told attendees.

“The main takeaway is that this study really focused on higher risk populations that traditionally would likely not have as easy access [to DoxyPEP] for numerous reasons,” said Christopher Foltz, MD, an infectious diseases specialist at Cedars-Sinai Infectious Diseases in Los Angeles. “This has long been the challenge with any preventive measure: How do you get in to the people who need it the most?”

Although clinical trials revealed significant drops in STI rates after the use of DoxyPEP, real-world effectiveness may differ from efficacy demonstrated in clinical trials, and evidence is particularly limited for the southern US, Niehaus said. But the use of DoxyPEP has rapidly expanded into routine clinical practice throughout the US since DoxyPEP became available in 2023 and particularly since the CDC’s DoxyPEP guidelines were published in June 2024, she said.

“It’s important to ensure clinics have protocols so that all patients who are at risk should be offered Doxy prevention in an attempt to remove any provider bias and for continued efforts to educate high-risk populations,” said Foltz, who was not involved with the study. “With time, much like with PrEP for HIV, I have already seen more patients requesting Doxy, and universally more primary care and other providers offering it.”

The researchers conducted a retrospective analysis of a cohort of participants who either have HIV or who use preexposure prophylaxis (PrEP) and were receiving care at an academic HIV clinic in North Carolina. The 380 participants had been prescribed DoxyPEP between January 2022 and December 2025.

“Throughout this time period, there were no clinic-wide policies around DoxyPEP prescribing, leaving the decision to do so up to the clinician, so this was rather natural diffusion into practice,” Niehaus said.

Participants were a median 36 years old, and nearly all (95%) were men who have sex with men, with 2.4% transgender women, 0.8% assigned female at birth, and 1.8% heterosexual cisgender men. Half (50%) were Black, and 40% were White; 11% had Hispanic/Latine ethnicity. Most (69%) had private insurance (69%) while 12% were on Medicaid, 7% were on Medicare, and 12% self-paid for care.

About half the participants (51%) had HIV, and the other half (49%) took PrEP. Just over a third (36%) had had a bacterial STI within the previous 12 months before DoxyPEP was prescribed, including 46% of participants with HIV and 26% of PrEP users.

Relying on Duke Health electronic medical records, the researchers calculated incidence of gonorrhea, chlamydia, and syphilis diagnoses before and after implementation of DoxyPEP. During that period, approximately half the cohort had been prescribed DoxyPEP by October 2024. The follow-up period was a median of 22 months prior to DoxyPEP initiation and a median 19 months after.

The overall incidence of STIs was 57 cases per 100 person-years prior to DoxyPEP prescribing, which fell to 19 cases per 100 person-years in the period after DoxyPEP prescribing was implemented, an approximate two thirds drop (incidence rate ratio [IRR], 0.33, 95% CI, 0.27-0.41).

Declines in incidence were seen across all three STIs investigated. Gonorrhea incidence was cut in half, from 26 to 13 cases per 100 person-years (IRR, 0.50), and chlamydia incidence fell about 80% from 21 to 4 cases per 100 person-years (IRR, 0.19). Syphilis fell from 10 to 2 cases per 100 person-years.

The decreases in STI incidence were not explained by differences in testing patterns. Among PrEP users, quarterly testing coverage was a median 60% before DoxyPEP initiation and a median 58% afterward. Among people with HIV, the median quarterly testing coverage was 33% before and 34% after DoxyPEP prescribing.

There were also no differences observed in STI incidence based on a person’s history of STIs. The IRR was 0.29 for both those with an STI in the previous 12 months and for 64% of participants with no STI history in the past year.

Those without a recent bacterial STI would not have met inclusion requirements for the DoxyPEP clinical trial, “yet these individuals experienced a similar relative reduction in STI incidents after DoxyPEP initiation,” Niehaus noted. “These findings suggest that DoxyPEP may provide benefit across a broader range of risk profiles than those represented in original trials, perhaps especially in high-incidence areas like the southeast United States.”

In terms of potential barriers to DoxyPEP uptake, Foltz said that the initial concerns from the medical community have largely been addressed since there is not a high incidence of side effects with Doxy or concerns about significant population-level bacterial resistance.

“Unfortunately, high-risk populations typically live in areas with less access to general healthcare,” Foltz said. “Continued efforts to improve on this through creative means, such as mobile health clinics and telemedicine clinics, can improve community education and access to STI prevention.”

The challenge now, he added, is how to “re-create this on a much larger scale so we can really get the word out about Doxy and make it available to all of those who need it.”

The research was funded by DukeHealth. Niehaus and Foltz had no disclosures.

Tara Haelle has covered science and medicine for nearly two decades and is author of Vaccination Investigation and The Informed Parent: A Science-Based Resource for Your Child’s First Four Years. She is based in Dallas.