Implementation, Adherence to DoxyPEP Remains Low in At-Risk Groups

In a session dedicated to new frontiers in preventing sexually transmitted infections (STIs) at the Conference on Retroviruses and Opportunistic Infections 2025, held in San Francisco, doxycycline post-exposure prophylaxis (DoxyPEP) was the primary focus of several studies whose results were shared during the session. Collectively, the studies found that, although DoxyPEP was significantly effective in preventing STIs, the initial uptake and sustained use of the treatment was subpar in areas of San Francisco and Washington D.C.

DoxyPEP Effective in Preventing Chlamydia, Gonorrhea, Syphilis

The prevention of STIs is the primary use of DoxyPEP overall. DoxyPEP can prevent STIs such as chlamydia and syphilis in those who use it consistently. A study¹ presented during the session by Hyman Scott, MD, MPH, clinical research medical director at Bridge HIV in the San Francisco Department of Health, aimed to assess just how effective DoxyPEP is when used consistently for the prevention of gonorrhea specifically.

All participants of this study were from a large sexual health clinic in San Francisco, with all clients who were seen starting on November 30, 2022, offered DoxyPEP if they were being seen for sexual health services. Participants were evaluated for up to 5 quarters after their first prescription of DoxyPEP if they were prescribed for more than 90 days. This analysis lasted through September 24, 2024. Participants who had not been prescribed DoxyPEP were analyzed before and after April 2023 for at least 5 quarters. STI rates were predicted through an interaction of initiation, use, and duration of using DoxyPEP.

There were 4149 participants in the study, of which 2419 used DoxyPEP; the participants had a mean (SD) follow-up time of 3.13 (1.70) quarters and median age range of 30 to 39 years. A total of 89% were cisgender men, 33% were White, 24% were Hispanic/Latinx, 17% were Asian, 13% were multiracial, and 4% were Black. A total of 98.7% of the participants were prescribed pre-exposure prophylaxis (PrEP) in conjunction with DoxyPEP.

DoxyPEP users had a higher risk of an STI compared with non users (OR, 5.33; 95% CI, 4.11-6.90) before they started using DoxyPEP. This risk decreased after initiation, with the overall risk becoming similar for each group after the beginning of DoxyPEP use (OR, 1.21; 95% CI, 0.86-1.68). Incidence of STIs also decreased significantly (OR, 0.28; 95% CI, 0.24-0.35) in people using DoxyPEP, with gonorrhea also seeing a decline in incidence rate (OR, 0.45; 95% CI, 0.39-0.53).

“For context, this is similar to the efficacy that has been seen in the clinical trials and this is one of the first analyses that has shown a nearly 50% decline in STI and gonorrhea incidents in the setting of clinical petition,” said Scott.

Although DoxyPEP is effective in preventing STIs, uptake and adherence need to improve to be fully effective | Image credit: Rizwanvet - stock.adobe.com

Uptake, Adherence Still Low in Urban Settings

However, despite the clear efficacy of DoxyPEP in preventing all sorts of STIs in patients at high risk, the uptake and continued adherence to DoxyPEP is still lacking in studies focused on Washington D.C.² and San Francisco.³

The study focused on a cohort from Washington D.C.² looked into preventing STIs in people living with HIV. Specifically, this involved investigating the eligibility for DoxyPEP, use of DoxyPEP, diagnosis rates of STIs, and the effect of a DoxyPEP prescription on the incidence of STIs.

“As DoxyPEP prescribing begins to roll out, real world measurement of its uptake and use remains understudied among people with HIV,” said Amanda D. Castel, MD, MPH, FAAP, a professor in the department of epidemiology at the Milken Institute School of Public Health at George Washington University. “Prior research among DC cohort participants has found increasing STI rates among people with HIV, including among those who are not virally suppressed.”

According to Castel, the study started enrolling in 2011 and includes 13,000 patients with HIV who receive care at 14 clinical sites in Washington, D.C. Participants were eligible for DoxyPEP if they were men who have sex with men (MSM) or transwomen who have been diagnosed with any of gonorrhea, syphilis, or chlamydia during the observation period of January 1, 2019, to December 31, 2023. The number of prescriptions of DoxyPEP were measured against the number of patients who were eligible for DoxyPEP.

The potential effect of DoxyPEP prescribing and the diagnosis rates of STIs were calculated by assessing the proportion of diagnoses that were potentially avoided by using the efficacy trial results. The number needed to treat (NNT) was used to estimate efficiency of prescribing DoxyPEP for any STI, a concurrent STI, or 2 or more STIs in the previous year.

The researchers found that only a small number of eligible patients were prescribed DoxyPEP. “From 2019 to 2024, among 1564 DC cohort participants with at least 1 STI diagnosis, only 64, or 4%, were prescribed DoxyPEP,” said Castel. Of these participants, the median age was 43 years, 70% were Black, and 88% had been diagnosed with HIV after male-to-male sexual contact.

There was a modest increase in DoxyPEP prescriptions from 2023 to 2024, going from 18 to 46 prescriptions, but this was significantly lower than the 77% to 85% of participants who were DoxyPEP eligible of the 347 STI diagnoses. The NNT was 3.88 for anyone with at least 2 STIs and 5.32 for any STI when prescribing DoxyPEP to people with HIV who had any diagnosis of an STI in the previous 12 months.

“We believe that increasing awareness of DoxyPEP among people with HIV and focused efforts to increase prescribing by providers of DoxyPEP in an equitable manner are warranted,” said Castel.

Similarly, in San Francisco,³ researchers looked at patients eligible for DoxyPEP to estimate the continuum in these patients, with characteristics identified to assess whether any were associated with a drop-off.

Patients who were seen from December 2022 to December 2024 who had an indication for DoxyPEP were included in the study. Estimations were calculated for who received a prescription, who initiated the medication, and who adhered to DoxyPEP. All of these measures were self-reported by the participants.

There were 7436 patients eligible for DoxyPEP who were seen in the time frame at the Magnet Clinic in San Francisco, of which 60% of them were given a prescription. Only 61% of those who were prescribed DoxyPEP reported ever using the medication and only 61% of those who had used the treatment at least once had reported a high adherence, totaling 1627 participants and 22% of the overall cohort.

“Compared to the 22% overall, we have about 5 percentage points lower among those youngest patients [less than 30 years], 3 percentage points lower among our Black and African American patients, 9 percentage points lower among those who are unstably housed or homeless, and 8 percentage points lower among those living with HIV,” said Michael P. Barry, PhD, associate director for translational research at the Illinois Institute of Technology.

The researchers concluded that less than 25% of the eligible patients for DoxyPEP at the Magnet Clinic were adherent, significantly lower than needed to accomplish STI prevention.

“To ensure equitable population-level impacts of DoxyPEP, we might consider giving these patients special consideration,” said Barry. “Other providers may replicate our approach to determine which patients and [if] their populations could benefit from better DoxyPEP coverage.”

Overall, DoxyPEP is an effective method of preventing STIs such as gonorrhea, chlamydia, and syphilis, but both prescriptions and adherence need to improve to target those with the highest risk and prevent further spread.

References

1. Scott H, Romoan J, Spinelli MA, et al. High sustained effectiveness of doxycycline PEP for STI prevention after clinical implementation. Presented at Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 163
2. Ji YS, Barth SK, Castel AD, et al. DoxyPEP eligibility, use, and potential for STI reduction in a large HIV cohort in Washington, DC. Presented at Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 162
3. Barry MP, Bena J, Roman J, Scott H. The doxy-PEP continuum among patients receiving care at a sexual health clinic in San Francisco. Presented at Conference on Retroviruses and Opportunistic Infections 2025; March 9-12, 2025; San Francisco, CA. Abstract 164