HIV Pre-Exposure Prophylaxis (PrEP) has been used in France since 2016. Its effectiveness is no longer to be demonstrated. However, follow-up and adherence remain the main pitfalls. The main objective of this study was to identify factors associated with persistence or loss of PrEP follow-up. An historic cohort of PrEP users was compiled from the database of consultations in the Indre-et-Loire dedicated sexual health centers (CeGIDD) from June 2016 to June 2021. Kaplan-Meier curves were performed to compare the group of persistent PrEP users to the discontinuation group. Factors associated with PrEP discontinuation were identified using Cox modelling, considering time-dependent variables. Final variables included in the model were selected based on the Akaike Information Criterion (AIC) and clinical relevance. Over the period, 568 PrEP users were included in the cohort. Median follow-up was 2.3 years. A quarter of users were lost to follow-up within 3 months after PrEP initiation. Sexual risk reduction AIDS community-based support (HR = 0.65[0.42;0.99]), being in a couple (HR = 0.51[0.38;0.68]), and history of syphilis (HR = 0.57[0.40;0.81]) were significantly associated with persistence of follow-up. Remote consultations (HR = 2.74[1.63;4.61]), chemsex practices (HR = 2.01[1.29;3.14]), and side effects (HR=1.72[1.03;2.88]) were significantly associated with a loss of follow-up. These results suggest that more sexual risk reduction AIDS community-based counseling could be a key, necessary for supporting PrEP users in their follow-up pathway. Indeed, AIDS community-based support could be used to build a basis for developing safe pathways. Remote consultations could represent a response to the issue of access to PrEP. To create a significant impact on global HIV incidence, the PrEP offer must be extended, and at-risk PrEP users supported to maintain PrEP use.