Laura Galli1, Vincenzo Spagnuolo2, Alba Bigoloni2, Antonella D'Arminio Monforte3, Francesco Montella4, Andrea Antinori5, Antonio Di Biagio6, Stefano Rusconi7, Giovanni Guaraldi8, Simona Di Giambenedetto9, Marco Borderi10, Davide Gibellini11, Giada Caramatti12, Adriano Lazzarin13, Antonella Castagna13. 1. Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy galli.laura@hsr.it. 2. Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy. 3. Clinic of Infectious and Tropical Diseases, Department of Health Sciences, San Paolo Hospital, University of Milan, Milan, Italy. 4. Division of Infectious Diseases, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy. 5. Clinical Department, National Institute for Infectious Diseases, IRCCS, Lazzaro Spallanzani, Rome, Italy. 6. Infectious Diseases Unit, IRCCS AOU San Martino-IST, Genova, Italy. 7. Division of Infectious and Tropical Diseases, DIBIC 'Luigi Sacco', University of Milan, Milan, Italy. 8. Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy. 9. Institute of Clinical Infectious Diseases, Catholic University of the Sacred Heart, Rome, Italy. 10. Infectious Diseases Unit, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy. 11. Department of Pathology and Diagnostics, Microbiology Unit, University of Verona, Verona, Italy. 12. U.O. Riabilitazione Specialistica Disturbi Neurologici Cognitivo-Motori, Department of Clinical Neurosciences, IRCCS San Raffaele, Milan, Italy. 13. Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy Università Vita-Salute San Raffaele, Milan, Italy.
Abstract
OBJECTIVES: 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 withatazanavir/ritonavir monotherapy versus atazanavir/ritonavir triple therapy. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
RCT Entities:
OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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: Michael S Saag; Constance A Benson; Rajesh T Gandhi; Jennifer F Hoy; Raphael J Landovitz; Michael J Mugavero; Paul E Sax; Davey M Smith; Melanie A Thompson; Susan P Buchbinder; Carlos Del Rio; Joseph J Eron; Gerd Fätkenheuer; Huldrych F Günthard; Jean-Michel Molina; Donna M Jacobsen; Paul A Volberding Journal: JAMA Date: 2018-07-24 Impact factor: 56.272
Authors: Delphine Sculier; Gilles Wandeler; Sabine Yerly; Annalisa Marinosci; Marcel Stoeckle; Enos Bernasconi; Dominique L Braun; Pietro Vernazza; Matthias Cavassini; Marta Buzzi; Karin J Metzner; Laurent A Decosterd; Huldrych F Günthard; Patrick Schmid; Andreas Limacher; Matthias Egger; Alexandra Calmy Journal: PLoS Med Date: 2020-11-10 Impact factor: 11.069