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)

Simona Di Giambenedetto, Massimiliano Fabbiani, Eugenia Quiros Roldan, Alessandra Latini, G. D'Ettorre, Andrea Antinori, Antonella Castagna, Giancarlo Orofino, Daniela Francisci, Pierangelo Chinello, G. Madeddu, Pierfrancesco Grima, Manuela Colafigli, Andrea De Luca, A. Mondi, F. Lombardi, A. De Luca, A. Poggi, C. Viscoli, M. GalliA. Gori, Alessandra Latini, M. Giuliani, A. Pacifici, F. Pimpinelli, F. Solivetti, F. Stivali, Andrea Antinori, R. Bellagamba, R. Libertone, S. Mosti, P. Narciso, E. Nicastri, S. Ottou, M. Zaccarelli, N. Petrosillo, Pierangelo Chinello, E. Boumis, S. Cicalini, E. Grilli, M. Musso, M. S. Mura, M. C. Rossi, S. Leonardi, A. Lazzarin, Antonella Castagna, S. Nozza, B. Belfiori, B. Belfiori, A. Ruggieri, on behalf of the Atlas-M Study Group

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Background: 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. Methods: 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/mm3. 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 300mg of atazanavir/ 100mg of ritonavir once daily and 300mg 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, number NCT01599364. Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)1163-1171
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Issue number4
Publication statusPublished - Jan 1 2017


ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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