Long-acting injectable antiretroviral therapy (LAI-ART) could increase adherence to therapy, while maintaining excellent viro-immunologic control, reduce the risk of toxicity and drug interactions, and improve the overall quality of life of people living with HIV. The purpose of this study is to assess knowledge and acceptability to this new therapeutic modality in PLWH and their readiness to change their current treatment regimen in favour of the injectable one. An anonymous, multiple-choice self-completion questionnaire was offered at the Infectious and Tropical Diseases Unit of the ASST Spedali Civili of Brescia from June 2022 to June 2023 to every PLWH. We enrolled 500 subjects. Although just a few people are aware of the availability of LAI-ART (only 281 subjects, 56.2%), the acceptability toward this new therapeutic modality is quite good (432 subjects, 86.4%) and more than half of the study population have declared that they would like to replace oral therapy with intramuscular injections (320, 63%). Duration of HIV infection, gender and number of concomitant medications were not related to the cumulative propensity to LAI-ART, while age appeared to be an independent predictor (OR 0.97, 95%CI 0.95-0.98, p-value < 0.001). The selection of motivated patients seems critical to establish LAI-ART in clinical practice.