Abstract
BACKGROUND: Over the past two decades, sexually transmitted infections (STIs) have increased substantially. Doxycycline post-exposure prophylaxis (DoxyPEP) has emerged as an effective preventive strategy for men who have sex with men (MSM) engaging in high-risk sexual behaviors. When taken within 72 h after condomless sexual exposure, doxycycline significantly reduces the incidence of bacterial STIs, including syphilis, chlamydia, and, partially, gonorrhea, without major severe adverse effects reported. This study aimed to describe the profile of individuals most suitable for DoxyPEP and to identify factors associated with its use among MSM receiving pre-exposure prophylaxis (PrEP) at the STI clinic of Policlinico Umberto I in Rome. METHODS: We enrolled 206 MSM receiving PrEP, either in a daily or on-demand regimen, between April 2025 and February 2026. Participants completed a structured questionnaire assessing sexual behaviors (number of partners, condom use, chemsex), STI diagnoses during PrEP use, and DoxyPEP use in the previous three months. Categorical variables were reported as absolute frequencies and percentages, and continuous variables as medians with interquartile ranges (IQR). For univariate analysis, participants were stratified according to DoxyPEP use (yes/no). Associations were assessed using the chi-square test or Mann–Whitney U test, as appropriate. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: The median age was 35 years (IQR 29–43). Overall, 81 participants (39.3%) reported DoxyPEP use in the previous three months, with a median of 2 administrations (IQR 1–3). Compared with non-users, DoxyPEP users more frequently reported more than five sexual partners in the previous six months (P= 0.005), longer PrEP use (P< 0.001), and a daily PrEP regimen (P= 0.001). They were less likely to report condom use (P= 0.009) and more likely to have a prior STI (P= 0.013). No associations were observed with age, ethnicity, education level, or chemsex. Full data are presented in Table 1. CONCLUSIONS: Despite the short observation period, DoxyPEP appears to be a targeted strategy for MSM with frequent high-risk exposures and prior STIs. These findings support its promotion among individuals with high-risk sexual behaviors and highlight the need for further studies to evaluate the long-term impact on STIs transmission and antimicrobial resistance. [Table: see text]