Background: Combination antiretroviral therapy (cART)-related toxicities and costs have prompted the need for treatment simplification. ATLAS-M trial explored 48-week non-inferior efficacy of simplification to atazanavir/ritonavir plus lamivudine versus maintaining three-drugs 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 plus two nucleoside reverse-transcriptase inhibitors (NRTI), with stable HIV-RNA<50 copies/mL, and CD4+>200 cells/mm3. Main exclusion criteria were: HBV-coinfection, past virological failure on or resistance to study drugs, recent AIDS, and pregnancy. Patients were randomly assigned 1:1 to either switch to atazanavir 300mg/ritonavir100mg once daily and lamivudine 300mg once daily (ATV/rit+3TC arm) or to continue the previous regimen (ATV/rit+2NRTI arm). Primary study outcome was the maintenance of HIV-RNA<50copies/mL at week 48 at the intention-to-treat-exposed (ITT-e) analysis with switch=failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, 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 119/133 patients (89.5%) in the ATV/rit+3TC arm and 106/133 patients (79.7%) in the ATV/rit+2NRTI arm (difference ATV/rit+3TC versus ATV/rit+2NRTI arm: +9.8% [95% CI +1.2 to +18.4]), demonstrating non-inferiority and superior efficacy of the ATV/rit+3TC arm. Virological failure occurred in two (1.5%) patients in the ATV/rit+3TC arm and six (4.5%) in the ATV/rit+2NRTI arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir plus lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir+2NRTI in virologically-suppressed patients.
Treatment simplification to atazanavir/ritonavir plus lamivudine versus maintenance of atazanavir/ritonavir plus two nucleoside reverse transcriptase inhibitors in virologically-suppressed HIV-1-infected patients : 48-weeks results from a randomized trial (ATLAS-M) / S. Di Giambenedetto, M. Fabbiani, E. Quiros Roldan, A. Latini, Ga. D’Ettorre, A. Antinori, A. Castagna, G. Orofino, D. Francisci, P. Chinello, G. Madeddu, P. Grima, S. Rusconi, M. Di Pietro, A. Mondi, N. Ciccarelli, A. Borghetti, E. Focà, M. Colafigli, A. De Luca, R. Cauda. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 1460-2091. - 72:4(2017 Jan), pp. 1163-1171.
Treatment simplification to atazanavir/ritonavir plus lamivudine versus maintenance of atazanavir/ritonavir plus two nucleoside reverse transcriptase inhibitors in virologically-suppressed HIV-1-infected patients : 48-weeks results from a randomized trial (ATLAS-M)
S. Rusconi;L. Taramasso
2017
Abstract
Background: Combination antiretroviral therapy (cART)-related toxicities and costs have prompted the need for treatment simplification. ATLAS-M trial explored 48-week non-inferior efficacy of simplification to atazanavir/ritonavir plus lamivudine versus maintaining three-drugs 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 plus two nucleoside reverse-transcriptase inhibitors (NRTI), with stable HIV-RNA<50 copies/mL, and CD4+>200 cells/mm3. Main exclusion criteria were: HBV-coinfection, past virological failure on or resistance to study drugs, recent AIDS, and pregnancy. Patients were randomly assigned 1:1 to either switch to atazanavir 300mg/ritonavir100mg once daily and lamivudine 300mg once daily (ATV/rit+3TC arm) or to continue the previous regimen (ATV/rit+2NRTI arm). Primary study outcome was the maintenance of HIV-RNA<50copies/mL at week 48 at the intention-to-treat-exposed (ITT-e) analysis with switch=failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, 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 119/133 patients (89.5%) in the ATV/rit+3TC arm and 106/133 patients (79.7%) in the ATV/rit+2NRTI arm (difference ATV/rit+3TC versus ATV/rit+2NRTI arm: +9.8% [95% CI +1.2 to +18.4]), demonstrating non-inferiority and superior efficacy of the ATV/rit+3TC arm. Virological failure occurred in two (1.5%) patients in the ATV/rit+3TC arm and six (4.5%) in the ATV/rit+2NRTI arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir plus lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir+2NRTI in virologically-suppressed patients.File | Dimensione | Formato | |
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