title: Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M).
abstract: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir  +  lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients.
  
  
  
  We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir + two NRTIs, with stable HIV-RNA <50 copies/mL and CD4 + >200 cells/mm 3 . Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300 mg of atazanavir/100 mg of ritonavir once daily and 300 mg of lamivudine once daily (atazanavir/ritonavir + lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir + two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch = failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364.
  
  
  
  Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir + lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir + two NRTIs arm [difference atazanavir/ritonavir + lamivudine versus atazanavir/ritonavir + two NRTIs arm: +9.8% (95% CI + 1.2 to + 18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir + lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir + lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir + two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms.
  
  
  
  Treatment simplification to atazanavir/ritonavir + lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir + two NRTIs in virologically suppressed patients.
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fabbiani
authors.affiliation: University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros Roldan
authors.affiliation: Infectious Dermatology and Allergology Unit, IFO S. Gallicano Institute (IRCCS), Rome, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Latini
authors.affiliation: Department of Infectious Diseases, 'La Sapienza' University, Rome, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Ettorre
authors.affiliation: National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: Department of Infectious and Tropical Diseases, Vita-Salute San Raffaele University, San Raffaele Hospital, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.affiliation: Infectious and Tropical Diseases Unit, Amedeo di Savoia Hospital, Torino, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Orofino
authors.affiliation: Infectious Diseases Clinic, University of Perugia, Perugia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Francisci
authors.affiliation: Systemic Infections and Immunodeficiency Unit, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Chinello
authors.affiliation: Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
authors.forename: Giordano
authors.initials: G
authors.lastname: Madeddu
authors.affiliation: Infectious Disease Unit, 'S. Caterina Novella' Hospital, Galatina, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Grima
authors.affiliation: Infectious Diseases Unit, DIBIC Luigi Sacco, University of Milan, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rusconi
authors.affiliation: Unit of Infectious Diseases, S.M. Annunziata Hospital, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Pietro
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mondi
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ciccarelli
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Borghetti
authors.affiliation: University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Focà
authors.affiliation: Infectious Dermatology and Allergology Unit, IFO S. Gallicano Institute (IRCCS), Rome, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Colafigli
authors.affiliation: UOC Malattie Infettive, Azienda Ospedaliera Universitaria Senese, Siena, Italy.|Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.affiliation: Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000706:statistics & numerical data; D000069446:Atazanavir Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D060085:Coinfection; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D019259:Lamivudine; D000069446:Atazanavir Sulfate; D019438:Ritonavir