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Introduction Antiretroviral therapy (ART) requires careful management due to the expanding range of available regimens, increasing comorbidities among people living with HIV (PLWH) and its economic impact on healthcare systems. In this context, collaboration between hospital pharmacists and infectious disease specialists may improve prescribing appropriateness, optimize treatment and support cost containment.Materials and Methods From March to December 2025, a collaborative program between the Hospital Pharmacy and the Infectious Diseases Unit was implemented to optimize antiretroviral regimens. Meetings were held every two months to review ongoing treatments, evaluate potential switches to less obsolete regimens with lower toxicity and jointly assess efficacy, tolerability and economic implications. Detailed reports were performed, documenting the clinical rationale for each modification and its associated pharmacoeconomic outcomes.Results A total of 630 PLWH are currently under care at our clinic. In 2024, ART-related expenditures amounted to € 3,836,710.71, representing a 5% increase compared with 2023 (€ 3,632,691.16), alongside 25 new patient referrals. Based on this trend, the projected additional expenditure for 2025 was estimated at € 200,543.Between March and December 2025, five multidisciplinary meetings were conducted. Figure 1 shows the 2024 and 2025 expenditure curves, showing a significant downward trend in spending compared with expectations, with annual total savings of € 72,912.73. During study period, 80 therapeutic switches were performed (13% of total regimens), of which 55 (69%) were to lower-cost options. Table 1 summarizes the main characteristics of the study population and the key features of the therapeutic changes. Protease inhibitor- and abacavir-based therapies markedly declined, whereas single-tablet formulations, doravirine- and tenofovir disoproxil fumarate-based treatments increased; integrase inhibitor-containing regimens remained stable.The main reasons for cost-reducing switches (figure 2) were treatment simplification (36%), proactive optimization (31%), and transition to long-acting injectable therapy (20%). Nearly one-third of high-cost switches were driven by virological failure. To date, no virological failures or treatment-related toxicities have been reported following the ART changes.Conclusion Therapeutic modifications implemented as part of the collaborative program led to a significant reduction in ART expenditure, representing a relevant pharmacoeconomic result. This was accompanied by a closer monitoring of ongoing regimens, associated with a marked decrease use of obsolete medications, reduction of pill burden, adoption of long-acting therapies and continuous optimization of patients’ cardiometabolic profiles. These findings support the effectiveness of a multidisciplinary collaboration in achieving optimized and sustainable management of ART.Abstract P35 Figure 1–2 and Table 1