Post-exposure prophylaxis with doxycycline (DoxyPEP) to prevent STIs in a real-world setting: the PRIDOX study

Area of Science:

• Public Health
• Infectious Diseases
• Clinical Pharmacology

Background:

• Sexually transmitted infections (STIs) remain a significant public health concern, particularly among men who have sex with men (MSM) using HIV pre-exposure prophylaxis (PrEP).
• Doxycycline post-exposure prophylaxis (DoxyPEP) has emerged as a potential strategy to curb STI incidence, but real-world data on its effectiveness and safety are crucial.

Purpose of the Study:

• To evaluate the real-world impact of DoxyPEP on the incidence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and syphilis (SPL) in a high-risk MSM cohort receiving HIV PrEP.
• To assess the safety and tolerability of DoxyPEP in this population and monitor for the emergence of multidrug-resistant (MDR) bacteria.

Main Methods:

• A prospective cohort study involving HIV PrEP users at high risk for STIs between March 2023 and August 2024.
• Incidence rates of CT, NG, and SPL were compared between pre-DoxyPEP and post-DoxyPEP periods using Cox proportional hazard models.
• Cultures for NG and MDR bacteria were performed, and antibiotic susceptibility testing was conducted.

Main Results:

• Of 876 PrEP users, 197 initiated DoxyPEP (98.4% MSM).
• DoxyPEP significantly reduced incidence rates for CT (31.4 to 7.8 per 100 person-years, P<0.001) and SPL (21.5 to 3.2 per 100 person-years, P<0.001).
• No significant reduction was observed for NG (41.5 to 28.9 per 100 person-years, P=0.1). NG isolates remained sensitive to ceftriaxone, and tetracycline resistance was comparable to controls. MDR bacteria prevalence remained stable.

Conclusions:

• DoxyPEP is well-accepted in routine PrEP care and significantly lowers STI incidence, demonstrating efficacy and safety in real-world settings.
• The study did not observe an increase in MDR bacteria or resistant NG strains with DoxyPEP use.
• Further research is warranted to fully understand DoxyPEP's long-term effects on bacterial resistance and the human microbiota.