Research continues to confirm that taking doxycycline after sex – an approach known as doxyPEP – reduces the risk of sexually transmitted infections. Two studies presented at the Conference on Retroviruses and Opportunistic Infections, which took place March 9-12 in San Francisco, looked at longer-term doxyPEP use in the city that rolled it out first.
In October 2022, the San Francisco Department of Public Health was the first to recommend doxyPEP, which involves taking a single dose of the antibiotic within 72 hours after sex. The Centers for Disease Control and Prevention recommends doxyPEP for cisgender gay and bisexual men and transgender women who have had an STI during the past year, but the DPH guidance is broader, including trans men and nonbinary people, as well as people with multiple sex partners who haven’t recently had an STI. At last year’s CROI, DPH researchers reported that preventive doxycycline contributed to a 50% decline in chlamydia and syphilis citywide, though there was little effect on gonorrhea.
At this year’s conference, San Francisco AIDS Foundation medical director Dr. Hyman Scott gave an update on the impact of doxyPEP after two years at SFAF’s Magnet sexual health clinic, which primarily serves gay and bi men and gender-diverse people. Magnet, part of the foundation’s Strut health center in the Castro, began rolling out doxyPEP in late November 2022, offering it to all eligible clients who received HIV PrEP or other sexual health services. The reception was enthusiastic, and initial doxyPEP demand and uptake were high.
This analysis included 2,524 people who were prescribed doxyPEP through September 2024 along with 2,068 nonusers. About 90% were cisgender men, about 10% were transgender or nonbinary, and the median age was 35.
Before starting doxyPEP, users had nearly a fourfold higher risk of STIs compared with nonusers. In the pre-doxyPEP period, STIs were rising steeply among users but falling among nonusers. In the post-doxyPEP period, there was a substantial drop in STIs among doxyPEP users while nonusers saw an ongoing shallow decline, so the difference between the two groups diminished. Among doxyPEP users, syphilis declined by 89%, chlamydia by 81%, and gonorrhea by 44%, all of which were statistically significant.
“This is similar to the efficacy that has been seen in clinical trials, and this is one of the first analyses that has shown a nearly 50% decline in gonorrhea incidence in a setting of clinical implementation of doxyPEP,” Scott said. These findings, he noted, indicate that those who could benefit most from doxyPEP are using it.
Asked why this study showed better efficacy against gonorrhea than others, Scott said that although doxyPEP guidelines say doxycycline can be taken up to 72 hours after sex, Magnet advises clients to take it within 24 hours – as the “last load of the night” – when it’s more likely to be effective.
In a second study, Michael Barry, Ph.D., MPH, and colleagues at SFAF looked at the doxyPEP continuum of care among Magnet clients who were eligible for doxycycline prophylaxis according to DPH guidelines and had at least two visits between December 2022 and December 2024.
Among the 7,436 clients with a doxyPEP indication, 59% received a prescription, according to their medical records. Of these, 61% (or 36% of the total eligible group) reported taking at least one dose of doxycycline. Of those, 61% (or 22% of the eligible group) reported high adherence, defined as consistent use within 72 hours after sex since their last visit.
The researchers saw some notable disparities based on age, gender identity, race/ethnicity, housing status, and HIV status. Transgender women were most likely to be prescribed doxyPEP (69%) and trans men the least likely (39%). Looking at the total population with a doxyPEP indication, high adherence was less likely among young people, Black people, unstably housed or homeless people, and people living with HIV versus HIV-negative people on PrEP.
Barry noted that the dramatic declines in STIs reported by Scott occurred despite low adherence to doxyPEP. “We’re seeing population-level impacts very likely due to doxyPEP uptake, but it could be even higher,” he said. “To ensure equitable population-level impacts of doxyPEP, we might consider giving these patients special consideration.”
It’s unclear how best to define good adherence to doxyPEP, as it might not be needed for all sexual encounters. For example, someone might use doxyPEP after a sex party but not after sex with a regular partner.
“I think our patients are very savvy at knowing which partners or which situations or which encounters will benefit from using this medication,” Barry told reporters at a conference news briefing.