- A Vancouver study piloted combined pre-exposure prophylaxis (PrEP) for HIV and bacterial STIs
- In addition to HIV PrEP, participants were offered doxycycline PrEP at different stages of the trial
- Chlamydia and syphilis infections only occurred among those who started doxycycline PrEP later
In Canada and other countries, rates of sexually transmitted infections (STIs)—particularly chlamydia, gonorrhea and syphilis—have been increasing over the past decade. As a population, gay, bisexual and other men who have sex with men (gbMSM) are at increased risk for STIs, as are transgender women. Clinical trials have found that taking doxycycline 200 mg within 72 hours after sexual exposure can significantly reduce the risk for the three main STIs previously mentioned. This use of doxycycline after potential STI exposure is called post-exposure prophylaxis (PEP). The use of doxyPEP is increasingly recommended by some physicians and public health authorities, such as the U.S. Centers for Disease Control and Prevention (CDC).
Multiple clinical trials have found that a pill called Truvada (containing TDF + FTC) is highly effective at reducing the risk of HIV when taken prior to potential exposure and when used as directed. This use of medicine prior to a potential exposure to reduce the risk of HIV infection is called pre-exposure prophylaxis (PrEP).
Given that people who use HIV PrEP are also at risk of acquiring STIs, a clinical trial exploring the use of both HIV and STI PrEP is needed.
About the study
A team of researchers in Vancouver at the BC Centre for Disease Control, the University of British Columbia and the BC Centre for Excellence in HIV/AIDS cooperated and designed a pilot study of daily Truvada + daily doxycycline for reducing the risk of both HIV and STIs. The focus of the study was to determine whether participants could take dual PrEP (for preventing HIV and STIs) and if it was tolerable.
Researchers enrolled 52 adults without HIV who were sexually active; most participants were gbMSM (48 people) and some were transgender or gender diverse. On average, participants were 35 years old and had a history of syphilis at some point in the past.
All participants were given Truvada, taken as a daily pill.
In addition, participants received a pill of doxycycline 100 mg to be taken daily. Half of the participants initiated daily doxycycline at the start of the study. The other half initiated daily doxycycline 24 weeks into the study. The duration of the study was 48 weeks.
Participants returned to the study clinic at regular intervals to give blood and urine samples for analysis. As well, swabs of the rectum and throat were done for bacterial cultures. At study visits, participants completed surveys and questionnaires about alcohol and drug use, depression, sexual health and possible medication-related side effects; they were also asked about their adherence to the study medicines. Also, at random clinic visits researchers had blood samples tested for levels of doxycycline.
Results
Adherence
In analyzing self-reports of adherence to the study medications, researchers found that there was no statistically significant difference between people who initiated doxycycline PrEP (doxyPrEP) immediately and those who deferred initiation until week 24.
However, when researchers reviewed blood samples for analysis of doxycycline at week 48, they found that adherence was 67% in people who initiated doxycycline at the start of the study vs. 29% in people who deferred initiation until week 24. This difference was statistically significant.
Adverse events
According to the researchers, among people who initiated doxycycline at the start of the study, adverse events (mostly nausea and diarrhea) were generally mild and resolved over time. Side effects were most frequently reported four weeks after initiating doxycycline.
Among people who deferred initiation of doxycycline, only one person reported an adverse event (mild nausea) four weeks after initiating doxycycline.
Infections
During the study there were no cases of HIV infection in either group.
Cases of chlamydia and syphilis occurred only in people who deferred initiation of doxycycline. However, gonorrhea occurred in people regardless of when they initiated the antibiotic.
Resistance
A concern with the chronic use of any antibiotic is the possibility that bacteria could develop the ability to resist the antibiotic. Researchers swabbed the nostrils of some participants before and after the study for the bacteria Staphylococcus aureus. At the start of the study, prior to initiating doxycycline, nine participants had S. aureus in their nostrils (three who subsequently initiated doxycycline immediately and six others who deferred initiation of the antibiotic), and none of the samples of bacteria had developed resistance to doxycycline.
Midway through the study, at week 24, nasal swabs from 12 participants found only one person (who initiated doxycycline at the start of the study) who had S. aureus that was resistant to doxycycline.
At week 48, researchers analysed swabs from a limited number of people. They found doxycycline-resistant S. aureus in four out of seven people who initiated the antibiotic at the start of the study and in one out of two people who initiated it at week 24.
As the study was small, definitive conclusions about the risk of antibiotic resistance cannot be made.
Bear in mind
Overall, researchers found that the combination of HIV PrEP + doxyPrEP was generally well tolerated. The antibiotic reduced the risk of STIs, mainly chlamydia and syphilis. The researchers stated that there were fewer cases of gonorrhea among people who initiated doxycycline at the start of the study. Among people who initiated doxycycline immediately, all cases of gonorrhea occurred in the throat. It is difficult to eradicate gonorrhea from the throat, as antibiotic levels there are not always optimal. This may particularly be the case with the 100 mg per day dose of doxycycline used in this study (rather than a higher dose of 200 mg). However, this issue requires further study.
An expert view
Professor Jeffrey Klausner, MD, from the University of Southern California has a long and successful history in public health programs and STI prevention. He reviewed the findings from the Vancouver study and other studies of doxycycline to prevent STIs. He stated that the overall risk-benefit ratio favours the use of doxycycline to prevent STIs. This is because several studies have found that the use of doxycycline significantly reduces the risk of STIs without a dramatic increase in resistance. These studies have occurred against a background of rising STIs rates.
Professor Klausner added that “overall, [the Vancouver] study findings provide reassurance that clinicians may safely initiate prophylaxis for both HIV and STIs at the same visit. Both were well tolerated and highly efficacious. The [Vancouver] study findings also confirm other studies regarding the effectiveness of daily doxycycline prophylaxis.” He further adds that “the findings by [the Vancouver researchers] confirm the evidence-based choices for STI prophylaxis include either doxycycline 200 mg within 72 hours after sex or 100 mg daily to prevent new infections. Giving patients choice empowers them, likely increases uptake and adherence and improved sexual health. More implementation science with doxycycline prophylaxis is urgently needed as well as a continued focus on the changing patterns in antimicrobial resistance at the population level.”
The data from the Vancouver study were used to design a much larger study that also explores the use of doxycycline to reduce the risk of STIs. Results from this larger study are expected in 2026.
—Sean R. Hosein
Resources
Doxycycline to help prevent bacterial STIs – CATIE
Sexually transmitted and blood-borne infections: Guides for health professionals – Public Health Agency of Canada
Doxy PEP for Bacterial STI Prevention – CDC
Exploring the impact of doxycycline to prevent sexually transmitted infections – CATIE News
Post-exposure doxycycline helps reduce the risk for some sexually transmitted infections – TreatmentUpdate 249
Sexually transmitted infection testing interventions: community and service provider preferences – CATIE
REFERENCES:
- Grennan T, Mohammed S, Edward J, et al. A pilot randomized controlled trial of dual daily HIV and sexually transmitted infection pre-exposure prophylaxis using tenofovir disoproxil fumarate/emtricitabine and doxycycline in gay, bisexual and other men who have sex with men and transgender women: The DuDHS Study. Clinical Infectious Diseases. 2025; in press.
- Klausner JD. A new choice for doxycycline prophylaxis. Clinical Infectious Diseases. 2025; in press.