The analysis presented shows the potential savings that LDR simplification strategies could lead to for the INHS, if applied widely. The main strength of the analysis is related to the data considered, which reflect the real clinical practice of the wards involved. PI-based dual therapies and monotherapies were taken into consideration in the analysis, including the ones considered off-label (ATV + r monotherapy) when detected within the hospitals. The main weakness of the model is that it does not take into consideration the costs of therapy switch, and considers only ART costs. Moreover, we assumed that all the patients eligible for a LDR simplification are switched to a dual therapy or monotherapy within the 3-year time horizon considered.