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Background and Importance Pre-exposure prophylaxis (PrEP) is a proven biomedical strategy to prevent HIV infection in high-risk populations, particularly men who have sex with men (MSM). It is considered a key public health intervention, especially when combined with routine sexually transmitted infection (STI) screening and risk-reduction counselling. Standardised protocols are essential to ensure consistent care, monitor safety, and promote adherence. Nonetheless, concerns persist regarding increased risk-taking behaviours and the potential rise in STI incidence among PrEP users.Aim and Objectives This study aimed to evaluate the effectiveness, tolerability, and adherence to PrEP in a tertiary hospital. Additionally, it sought to assess the incidence and recurrence of STIs during the follow-up period.Material and Methods A retrospective descriptive study was conducted between November 2021 and July 2025, involving 71 patients enrolled in the PrEP program. Data collected included demographic characteristics, clinical records, pharmacy dispensation, and laboratory findings. Adherence was assessed indirectly using pharmacy refill records, pill counts and SMAQ questionnaire. Safety was evaluated through side effect reports and biochemical alterations (renal function). Routine STI screenings were performed throughout follow-up.Results Of the 71 patients, 98.6% were male, with a median age of 38 ± 10 years. Mean treatment adherence was 98%, and the median duration of PrEP use was two years. No cases of HIV seroconversion were observed. Side effects were reported by 43.7% of patients, predominantly mild, transient gastrointestinal symptoms occurring early in treatment. Biochemical abnormalities, mainly decreased glomerular filtration rate or proteinuria, were noted in 21.1% of patients; however, no discontinuation of treatment was required. A total of 145 STIs were recorded during follow-up; 83.1% of patients had at least one, and 20.4% had more than three. The most frequently detected pathogens, in descending order of incidence, were Neisseria gonorrhoeae, Ureaplasma urealyticum, and Chlamydia trachomatis Conclusion and Relevance PrEP was highly effective and well tolerated. The high incidence of STIs highlights the need for ongoing screening and behavioural counselling. While the hospital protocol demonstrated safety and efficacy, enhanced follow-up and strengthened STI prevention measures are necessary to optimise long-term outcomes.Conflict of Interest No conflict of interest