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Background Doxycycline post-exposure prophylaxis (doxy-PEP) is an emerging strategy to reduce sexually transmitted infections (STIs) among individuals at high risk. Despite growing evidence of its effectiveness, uptake remains limited and heterogeneous. Identifying missed opportunities (MO) for doxy-PEP use in the presence of risk factors is crucial to optimize prevention strategies. Within the PRIDE cohort, we aimed to quantify MO and identify factors associated with non-use, including the role of counselling.Methods We conducted a cross-sectional analysis of visits within the PRIDE cohort, including people with at least one predefined STI risk factor: chemsex, group sex, >50 sexual partners in the previous 3 months, or sex work. Missed opportunities were defined as non-use of doxy-PEP in the presence of at least one risk factor in the prior 3 months. Demographic, behavioral, and clinical variables were analyzed. Logistic regression models with robust standard errors clustered by participant ID were used to account for repeated visits within individuals and to identify factors associated with MO.Results We included 1,387 people for a total of 2,390 visits, including 909 doxy-PEP use and 1,481 MO ( table 1). Participants were predominantly cisgender men (92.1%), with a mean age of 40.5 (±9.7) years. MO were more frequent among individuals with shorter time on PrEP and lower educational levels, and among transgender individuals. In addition, MO remained frequent across individuals reporting chemsex (227/420, 54.0%), group sex (1,216/2,067, 58.8%), and sex work (217/268, 81.0%).In multivariable analysis, longer time on PrEP was associated with lower odds of MO (OR 0.80, 95% CI 0.75–0.85), whereas female cisgender (OR 11.9, 95% CI 1.76–80.85) and transgender individuals (OR 8.97, 95% CI 3.20–25.15) had higher odds of non-use (table 2). Behavioural factors associated with a lower likelihood of MO included a high level of education (OR 0.64, 95% CI 0.49 – 0.83), chemsex use (OR 0.56, 95% CI 0.42–0.74) and group sex (OR 0.12, 95% CI 0.05–0.26), as well as higher numbers of sexual partners. Conversely, MenB vaccination was associated with increased odds of MO (OR 1.84, 95% CI 1.38–2.45).Among individuals with MO, prior doxy-PEP use was associated with longer time on PrEP, higher likelihood of counselling, and higher prevalence of high-risk behaviours, including sex work and a higher number of sexual partners (table 3). Counselling was strongly associated with doxy-PEP use, both at the current visit and in previous visits.Conclusion Missed opportunities for doxy-PEP use remain frequent among individuals at high risk for STIs in the PRIDE cohort. Uptake is influenced by demographic, behavioral, and structural factors, including time on PrEP, gender identity, education, and counselling exposure. Targeted interventions, particularly improved and systematic counselling, may reduce disparities and increase doxy-PEP uptake among underserved populations.Abstract OC27 Table 1–3