Doxycycline post-exposure prophylaxis (doxy-PEP) is emerging as a promising strategy to combat the rising rates of bacterial sexually transmitted infections (STIs). Recent clinical trials have demonstrated its effectiveness in reducing the incidence of gonorrhea, chlamydia, and syphilis, particularly among men who have sex with men (MSM) and transgender women (TGW) at high risk. However, the widespread adoption of doxy-PEP necessitates a careful evaluation of its potential benefits and risks, including the development of antibiotic resistance and alterations to the microbiome.
Efficacy of Doxy-PEP in Clinical Trials
Several key trials have highlighted the efficacy of doxy-PEP in reducing bacterial STI incidence. The IPERGAY study, conducted in France, showed a 47% relative risk reduction in time to first incident STI (syphilis or chlamydia) among MSM using event-driven PrEP. The DoxyPEP trial in the US demonstrated a significant 65% relative risk reduction for all three bacterial STIs (gonorrhea, chlamydia, and syphilis) at 12 months in MSM and TGW, regardless of HIV status. Similarly, the DOXYVAC trial found an 84% relative risk reduction in chlamydia and syphilis and a 51% reduction in gonorrhea among MSM on PrEP.
However, the dPEP Kenya study, which focused on cisgender women taking PrEP, found no statistical difference in chlamydia incidence between the doxy-PEP and standard of care groups. This lack of efficacy was attributed to suboptimal adherence to doxy-PEP in the study population.
Balancing Benefits and Risks
While doxy-PEP has shown considerable promise, concerns remain about its potential long-term consequences. One major concern is the emergence of antibiotic resistance in STI pathogens, particularly Neisseria gonorrhoeae. Mathematical modeling suggests that widespread doxy-PEP use could lead to the predominance of tetracycline-resistant strains within a decade, diminishing its effectiveness for gonorrhea prevention.
Additionally, there are concerns that doxy-PEP could increase the risk of resistance in bystander bacteria, such as Staphylococcus aureus and Streptococcus pneumoniae, potentially leading to severe infections with limited treatment options. Studies have also explored the impact of doxy-PEP on the gut microbiome, with some evidence suggesting potential alterations in bacterial composition.
Implementation and Future Directions
Despite these concerns, the implementation of doxy-PEP has begun in several communities, with the San Francisco Department of Public Health being among the first to release recommendations. Uptake has been promising, particularly among individuals with a higher number of sex partners, suggesting that the intervention can be successfully targeted to those who might benefit most.
Moving forward, it is crucial to proactively design and monitor doxy-PEP implementation using an equity lens, ensuring that key populations at risk have access to this intervention while minimizing the risk of excess antibiotic exposure. Further research is needed to address areas of clinical uncertainty, such as optimal STI screening intervals, the management of contacts of individuals with STIs who are taking doxy-PEP, and the potential for emergent resistance in Chlamydia trachomatis and Treponema pallidum.
Ultimately, the decision to prescribe or use doxy-PEP should result from a shared decision-making process between the healthcare practitioner and the patient, carefully weighing the benefits and risks. As real-world implementation data become available, ongoing monitoring of uptake, impact on antibiotic resistance, and population-level STI rates will be essential to inform future guidelines and optimize the use of doxy-PEP as a valuable tool in the fight against STIs.
