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

To assess the impact of doxycycline post-exposure prophylaxis (DoxyPEP) on Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and syphilis (SPL) incidence in a high-risk MSM cohort in a real-world setting.

HIV pre-exposure prophylaxis (PrEP) users at high risk of sexually transmitted infections (STIs) seen in our clinic between March 2023 and August 2024 were offered DoxyPEP. The incidence of the first CT, NG and SPL episode was compared between pre-DoxyPEP and post-DoxyPEP periods using Cox proportional hazard models. NG and MDR bacteria cultures were also conducted.

Among 876 PrEP users, 197 (22.4%) were eligible and initiated DoxyPEP; 98.4% were MSM. Incidence rates per 100 people per year for the first STI episode in the pre- and post-DoxyPEP periods were: 31.4 and 7.8 (P = 0.0001) for CT, 41.5 and 28.9 (P = 0.1) for NG, and 21.5 and 3.2 (P = 0.0001) for SPL. NG culture was positive in 14 (29.7%) of 47 NG infections detected by PCR in the post-DoxyPEP period. All isolates were sensitive to ceftriaxone, and resistance to tetracyclines was similar to those not on DoxyPEP (42.7% versus 46.3%, P = 0.23). DoxyPEP was discontinued in nine (4.5%) participants. Prevalence of MDR bacteria was similar at baseline and at 48 weeks (10.6% versus 8.2%; P > 0.5).

DoxyPEP was well accepted within routine PrEP care, significantly reducing STI incidence with good tolerance. Our data show its efficacy and safety in real-world settings. The emergence of MDR bacteria or resistant NG was not observed. However, its impact on bacterial resistance and the microbiota requires further evaluation.