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)

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.