Aims: To assess the cumulative rate of HIV Pre-Exposure Prophylaxis (PrEP) users in Brazil since its 2018 implementation and to analyze the association between PrEP usage and state-level structural factors. Methods: A nationwide ecological study from 2018 to 2022 was conducted, examining the 5-year cumulative rate of PrEP users in relation to demographic, socioeconomic, and healthcare infrastructure variables. Multiple linear regression analysis identified significant predictors of PrEP utilization. Results: Between 2018 and 2022, 124,796 individuals used PrEP, with a cumulative rate of 61.5 per 100,000 population. The highest usage was in Minas Gerais, São Paulo, and Santa Catarina, while the lowest was in Distrito Federal, Maranhão, and Alagoas. Regression analysis showed that higher PrEP usage was associated with lower population density, a younger median age, a lower male to female ratio, and reduced social vulnerability. Additionally, PrEP usage was positively associated with the density of medical doctors and the number of dispensing units. Conclusions: The study reveals significant regional disparities in PrEP usage across Brazil, influenced by socioeconomic and healthcare factors. It highlights the need for targeted public health strategies to enhance PrEP access and uptake, especially in socially vulnerable regions.