Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial.

Abstract

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. 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. 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. 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.