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

作者：Fabbiani Massimiliano^*; Gagliardini Roberta; Ciccarelli Nicoletta; Roldan Eugenia Quiros; Latini Alessandra; d'Ettorre Gabriella; Antinori Andrea; Castagna Antonella; Orofino Giancarlo; Francisci Daniela; Chinello Pierangelo; Madeddu Giordano; Grima Pierfrancesco; Rusconi Stefano; Del Pin Barbara; Lombardi Francesca; D'Avino Alessandro; Foca Emanuele; Colafigli Manuela; Cauda Roberto; Di Giambenedetto Simona; De Luca Andrea

来源：Journal of Antimicrobial Chemotherapy, 2018, 73(7): 1955-1964.

DOI：10.1093/jac/dky123

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.
Methods: 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/mm(3). 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.
Results: 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.
Conclusions: 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.

• 出版日期2018-7