title: Atazanavir/ritonavir monotherapy: 96 week efficacy, safety and bone mineral density from the MODAt randomized trial.
abstract: To report the 96 week results on efficacy, safety and bone mineral density (BMD) in subjects with HIV-1 that were virologically suppressed and treated with atazanavir/ritonavir monotherapy versus atazanavir/ritonavir triple therapy.
  
  
  
  MODAt is a prospective, multicentre, open-label, non-inferiority, randomized, 96 week trial (NCT01511809) comparing efficacy of atazanavir/ritonavir monotherapy versus atazanavir/ritonavir triple therapy. Treatment success was defined as no occurrence of confirmed viral rebound (two consecutive HIV-RNA >50 copies/mL) or discontinuation for any cause of the ongoing regimen.
  
  
  
  The 96 week treatment success was 64% in the atazanavir/ritonavir monotherapy arm and 63% in the triple-therapy arm (difference 1.3%, 95% CI: -17.5 to 20.1). In the atazanavir/ritonavir monotherapy arm, no PI- or NRTI-associated resistance mutations were observed at virological failure and all patients re-suppressed after re-intensification. In the monotherapy arm, treatment failure was more frequent in patients coinfected with hepatitis C virus [64% versus 28% (difference 35.4%, 95% CI: 3.7-67.2)]. Drug-related adverse events leading to discontinuation were 3 (6%) in the atazanavir/ritonavir monotherapy arm and 11 (21.5%) in the triple-therapy arm (P = 0.041). The 96 week adjusted mean percentage change in total proximal femur (not at lumbar spine) BMD was +1.16% and -1.64% in the atazanavir/ritonavir monotherapy arm and the triple-therapy arm, respectively (P = 0.012).
  
  
  
  The 96 week analyses suggested that long-term efficacy of atazanavir/ritonavir monotherapy was inferior as compared with atazanavir/ritonavir triple therapy, particularly when administered in subjects coinfected with hepatitis C virus. In the atazanavir/ritonavir monotherapy arm, reintroduction of nucleosides, as needed, was always effective with no new resistance mutation; monotherapy was also associated with a lower incidence of adverse events and improvement in femur BMD.
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy galli.laura@hsr.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Spagnuolo
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Bigoloni
authors.affiliation: Clinic of Infectious and Tropical Diseases, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: D'Arminio Monforte
authors.affiliation: Division of Infectious Diseases, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montella
authors.affiliation: Clinical Department, National Institute for Infectious Diseases, IRCCS, Lazzaro Spallanzani, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Infectious Diseases Unit, IRCCS AOU San Martino-IST, Genova, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Biagio
authors.affiliation: Division of Infectious and Tropical Diseases, DIBIC 'Luigi Sacco', University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.affiliation: Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Guaraldi
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.affiliation: Infectious Diseases Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Borderi
authors.affiliation: Department of Pathology and Diagnostics, Microbiology Unit, University of Verona, Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.affiliation: U.O. Riabilitazione Specialistica Disturbi Neurologici Cognitivo-Motori, Department of Clinical Neurosciences, IRCCS San Raffaele, Milan, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Caramatti
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006526:Hepatitis C; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D000069446:Atazanavir Sulfate; D019438:Ritonavir