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Background: The purpose of this study was to describe temporal trends in the use of antiretroviral therapy (ART) among people living with HIV (PLWHIV) from the cohort of the Spanish HIV/AIDS research network (CoRIS), 2004–2020. Methods: We described the yearly evolution of the proportion of patients receiving ART and the most frequently prescribed antiretroviral drugs among newly recruited treatment-naïve patients and among all patients with active follow-up. Results: Of 15,539 patients included, 14,618 (94.1%) started ART during their follow-up. Regarding initial regimens, the use of 2NRTI plus 1NNRTI (which were the most frequently prescribed until 2014) and 2NRTI plus 1bPI decreased after 2014, being gradually replaced by INI-based triple therapies. Since 2019, other regimens started to be prescribed, mainly dual therapies. TDF/FTC/EFV was the single-tablet regimen (STR) most frequently prescribed as initial ART until 2012, decreasing thereafter as TDF/FTC/RPV, TDF/FTC/EVG/COBI, and ABC/3TC/DTG became available. TAF/FTC/BIC accounted for 53.6% of initial prescriptions in 2020, followed by DTG/3TC (24%). The percentage of patients on ART increased from 45.7% in 2004 to 98.2% in 2020. Among all patients receiving ART, regimens based on 2NRTI plus 1INI increased from 0.1% in 2007 to 53.3% in 2020. During 2007–2015, most patients were receiving TDF/FTC/EFV, which was replaced after 2017 by ABC/3TC/DTG. In 2020, 13.0% of patients were receiving dual therapies. Conclusions: Robust real-world data on ART use in PLWHIV over more than 15 years show historical trends in prescriptions with an unprecedented visualization of the contemporary treatment patterns.

Temporal Trends and Geographic Variability in the Prescription of Antiretroviral Treatments in People Living with HIV in Spain, 2004–2020