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Monica Tontodonati,1,2 Giovanni Cenderello,3 Benedetto Maurizio Celesia,4 Michele Trezzi,5 Tamara Ursini,2 Andrea Costantini,6 Domenico Marra,7 Ennio Polilli,8 Corrado Catalani,5 Luca Butini,6 Federica Sozio,8 Elena Mazzotta,9 Antonina Sciacca,8 Giuliano Rizzardini,10 Lamberto Manzoli,11 Alessandro Cozzi-Lepri,12 Giustino Parruti8 1Infectious Disease Unit, Pescara General Hospital, Pescara, 2Clinic of Infectious Diseases, G D'Annunzio University of Chieti-Pescara, Chieti, 3Division of Infectious Disease, Galliera General Hospital, Genoa, 4Infectious Diseases Unit, ARNAS Garibaldi, Catania, 5Infectious Diseases Unit, Pistoia General Hospital, Pistoia, 6Clinical Immunology Unit, Ancona Hospital, Ancona, 7Division of Oncology, Galliera General Hospital, Genoa, 8Infectious Diseases Unit, Pescara General Hospital, Pescara, 9Internal Medicine Department, G D'Annunzio University of Chieti-Pescara, Chieti, 10First Infectious Diseases Department, Luigi Sacco Hospital, Milan, 11Section of Hygiene, Epidemiology, Pharmacology and Legal Medicine, G D'Annunzio University of Chieti-Pescara, Chieti, Italy; 12Research Department of Infection and Population Health, University College London, London, UK Background: As HIV infection turned into a chronic treatable disease, now ranking as one of the most costly in medicine, long-term sustainability of highly active antiretroviral treatment (HAART) expenses became a major issue, especially in countries with universal access to care. Identification of determinants of higher HAART costs may therefore help in controlling costs of care, while keeping high levels of retention in care and viral suppression. Methods: With this aim, we enrolled a large multicentric sample of consecutive unselected human immunodeficiency virus (HIV) patients followed at five sites of care in Italy, and evaluated annual individual HAART costs in relation to a number of sociodemographic, clinical, and laboratory variables. Results: We enrolled 2,044 patients, including 1,902 on HAART. Mean HAART costs were €9,377±€3,501 (range 782–29,852) per year, with remarkable site-based differences, possibly related to the different composition of local assisted populations. Percentages of patients on viral suppression were homogeneously high across all study sites. The factors identified by cross-validation were line of HAART, diagnosis of acquired immune deficiency syndrome, current CD4 T-cell count, and detectable HIV viremia >50 copies/mL. In the final multivariable model, HAART costs were independently directly associated with more advanced HAART line (P