Massimiliano Fabbiani1, Roberta Gagliardini2,3, Nicoletta Ciccarelli2, Eugenia Quiros Roldan4, Alessandra Latini5, Gabriella d'Ettorre6, Andrea Antinori7, Antonella Castagna8, Giancarlo Orofino9, Daniela Francisci10, Pierangelo Chinello11, Giordano Madeddu12, Pierfrancesco Grima13, Stefano Rusconi14, Barbara Del Pin15, Francesca Lombardi2, Alessandro D'Avino2, Emanuele Focà4, Manuela Colafigli5, Roberto Cauda2, Simona Di Giambenedetto2, Andrea De Luca3. 1. Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 2. Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy. 3. Infectious Diseases Unit, Siena University Hospital and Department of Medical Biotechnologies, University of Siena, Siena, Italy. 4. University Division of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. 5. Infectious Dermatology and Allergology Unit, IFO S. Gallicano Institute (IRCCS), Rome, Italy. 6. Department of Infectious Diseases, 'La Sapienza' University, Rome, Italy. 7. National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy. 8. Department of Infectious and Tropical Diseases, Vita-Salute San Raffaele University, San Raffaele Hospital, Milan, Italy. 9. Infectious and Tropical Diseases Unit, Amedeo di Savoia Hospital, Turin, Italy. 10. Infectious Diseases Clinic, University of Perugia, Perugia, Italy. 11. Systemic Infections and Immunodeficiency Unit, National Institute for Infectious Diseases 'Lazzaro Spallanzani' IRCCS, Rome, Italy. 12. Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. 13. Division of Infectious Diseases, 'S. Caterina Novella' Hospital, Galatina, Italy. 14. Infectious Disease Unit, DIBIC Luigi Sacco, University of Milan, Milan, Italy. 15. Unit of Infectious Diseases, S.M. Annunziata Hospital, Florence, Italy.
Abstract
Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults onatazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
RCT Entities:
Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.
Authors: Mary Clare Masters; Karen M Krueger; Janna L Williams; Lindsay Morrison; Susan E Cohn Journal: Expert Rev Clin Pharmacol Date: 2019-12 Impact factor: 5.045
Authors: Jonathan Z Li; Paul E Sax; Vincent C Marconi; Jesse Fajnzylber; Baiba Berzins; Amesika N Nyaku; Carl J Fichtenbaum; Timothy Wilkin; Constance A Benson; Susan L Koletar; Ramon Lorenzo-Redondo; Babafemi O Taiwo Journal: Open Forum Infect Dis Date: 2019-02-11 Impact factor: 3.835