Doxycycline on the Rise: A Double-Edged Sword

As doxycycline post-exposure prophylaxis (doxyPEP) gains traction in the fight against sexually transmitted infections (STIs), experts are raising alarms over increasing antibiotic resistance. At a recent symposium during the 13th International AIDS Society Conference on HIV Science (IAS 2025), panelists shed light on some critical challenges facing doxyPEP implementation.

What is DoxyPEP?

DoxyPEP involves taking a 200mg dose of doxycycline within 72 hours post-coitus to stave off infections such as chlamydia, syphilis, and gonorrhoea. A 2022 study revealed promising results among men who have sex with men and transgender women in San Francisco and Seattle, dramatically lowering STI risk. However, the picture isn't all rosy. Trials in France indicated a concerning drop in effectiveness against gonorrhoea, likely tied to rising drug resistance. A separate study of young cisgender women in Kenya found doxyPEP largely ineffective due to inconsistent usage.

Expert Insights on DoxyPEP's Future

During the conference, Professor Annie Luetkemeyer from the University of California San Francisco offered valuable solutions for overcoming clinical hurdles in doxyPEP delivery. She, alongside Professor Elizabeth Bukusi from the Kenya Medical Research Institute and Professor Jean-Michel Molina from Hôpital St Louis in Paris, discussed strategies to navigate the looming threat of antimicrobial resistance, a topic aptly dubbed 'the elephant in the room' by moderator Dr. Troy Grennan.

Guidelines Emerge Amidst Resistance Concerns

Since the initial trial findings, cities around the world have begun issuing doxyPEP guidelines. San Francisco, the pioneer in this respect, recommends doxyPEP for anyone engaging in condomless sex with at least one partner, irrespective of recent STI history—underscoring the need for proactive health measures. Conversely, Australia's recent guidelines tread lightly, and nations like Belgium and the Netherlands hesitate to endorse doxyPEP for STI prevention.

The Growing Specter of Antibiotic Resistance

The primary worry around doxyPEP is its potential to escalate antibiotic resistance, especially concerning gonorrhoea. This pathogen is already known to exhibit resistance to tetracyclines, the drug family encompassing doxycycline. Alarmingly, it can even share resistance genes with other bacterial species, compounding the threat.

New Findings Raise Red Flags

Recent data from the San Francisco and Seattle trial provided some initial comfort regarding antibiotic resistance, but a new report out just before the conference signaled a worrying trend: extensively drug-resistant gonorrhoea is on the rise. Analysis by Dr. David Helekal from Harvard revealed the troubling growth of resistant strains, highlighting a shift in gonococcal populations linked to the increased use of doxycycline for both treatment and prevention.

Global Perspectives on Resistance Levels

Resistance levels vary significantly across regions, with northwest America leading the way. High-level tetracycline resistance among gonorrhoea cases spiked dramatically in Seattle following the introduction of doxyPEP. Meanwhile, a comprehensive review indicated even higher resistance rates globally, particularly in Europe and sub-Saharan Africa.

Caution is Key: Experts Weigh In

While doxyPEP is generally safe and effective, there are long-standing uncertainties to consider. Experts urge ongoing monitoring of resistance trends and suggest a more cautious approach to prescribing, recommending limiting doses to one or two per week.

Advocating for Young Women at Risk

Professor Bukusi stressed that young women in Africa face heightened exposure to STIs, emphasizing the urgency of finding reliable prophylaxis methods. As her team wraps up research into consistent doxyPEP usage for cisgender women, the findings may provide critical insights, particularly as previous studies were hindered by COVID-19 disruptions.

The Road Ahead for DoxyPEP

The experts concur that while doxyPEP shows promise in preventing chlamydia and syphilis, the challenge will be how to effectively tackle gonorrhoea given the escalating resistance. As research continues and guidelines evolve, the pressing question remains: how do we ensure doxyPEP is both safe and effective in the long run?