Simplification to Atazanavir/Ritonavir + Lamivudine versus Maintaining Atazanavir/Ritonavir + 2NRTIs in Virologically Suppressed HIV-infected Patients: 48-weeks Data of the ATLAS-M Trial

Objectives: To explore 48-weeks non-inferior efficacy of treatment simplification to atazanavir/ritonavir+lamivudine versus maintaining 3-drugs atazanavir/ritonavir-based cART. Methods: ATLAS-M is a phase IV, multicenter, open-label, randomized study. Subjects on atazanavir/ritonavir+2NRTIs, without previous virological failures(VF), with HIV-RNA< 50copies/mL for >3months and CD4>200cells/mm3 for >6months were eligible. At baseline, patients were randomized to switch to atazanavir/ritonavir+lamivudine(dual therapy,DT) or to maintain the 3-drug regimen(triple therapy,TT). Primary endpoint: proportion of patients free of treatment failure(TF) at week 48. TF was defined as treatment modification for any reason, including VF(2 consecutive HIV-RNA>50copies/mL or a single value >1,000copies/mL). Results: A total of 266 patients(78% males, median age 44 years, median CD4 603cells/μL, 79% treated with tenofovir) were enrolled. Forty-eight weeks data were available for 128 and 128 patients in DT and TT arm,respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 48 weeks, at the intention-to-treat switch=failure analysis the proportion of patients free of TF was 89.8%(95%CI 84.6-95.0) and 79.7%(95%CI 72.7-86.7) in DT and TT arm, respectively(difference +10.1%, 95%CI +1.4/+18.8). VF was observed in 2(1.6%) patients randomized to DT and 6(4.7%) to TT. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 48, no significant differences in CD4 were observed between the two arms(+68 vs +33 cells/μL,p=0.210). A greater increase in total cholesterol(+14 vs -3 mg/dL,p< 0.001) and HDL(+4 vs +0 mg/dL,p< 0.001) was observed in DT arm without differences of other lipid parameters. Renal function showed a significant improvement in DT arm(mean change in eGFR +2 vs -4 mL/min/1.73m2 in TT,p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between study arms. Conclusion: 48-weeks data clearly indicate non-inferiority and suggest a possible superior efficacy of treatment simplification to atazanavir/ritonavir+lamivudine as compared to continuation of atazanavir/ritonavir+2NRTIs in virologically suppressed patients.