Safety and feasibility of treatment simplification to atazanavir/ritonavirlamivudine in HIV-infected patients on stable treatment with two nucleos(t)ide reverse transcriptase inhibitorsatazanavir/ritonavir with virological suppression (Atazanavir and Lamivudine for treatment Simplification, AtLaS pilot study)

To explore 48 week safety and efficacy of treatment simplification to atazanavir/ritonavirlamivudine in HIV-infected patients with virological suppression on a stable atazanavir/ritonavir-based standard triple regimen. This was a single-arm pilot study, enrolling 40 patients on atazanavir/ritonavirtwo nucleos(t)ide reverse transcriptase inhibitors (NRTIs), without previous treatment failure, with HIV-RNA 50 copies/mL for 3 months and CD4 200 cells/mm(3). At baseline, patients were switched to 300/100 mg of atazanavir/ritonavir300 mg of lamivudine once daily. Laboratory parameters, atazanavir plasma levels, self-reported adherence, quality of life, neurocognitive performance, bone composition and body fat distribution were monitored. Virological failure was defined as HIV-RNA 50 copies/mL on two consecutive determinations or a single level 1000 copies/mL. After 48 weeks, 4/40 (10) regimen discontinuations occurred: 1 death (brain haemorrhage), 1 study withdrawal (inadequate atazanavir plasma levels), 1 re-induction with two NRTIs due to pregnancy and 1 virological failure without development of resistance. Seven moderate to severe adverse events were recorded (including four renal colics, possibly treatment-related) in six patients. At week 48, increases in total (mean change 17 mg/dL, P0.001), high-density lipoprotein (6 mg/dL, P0.001) and low-density lipoprotein (8 mg/dL, P0.052) cholesterol were observed. The glomerular filtration rate improved (7 mL/min/1.73 m(2), P0.001), as did scores exploring self-reported physical and mental health (11, P0.009 and 13, P0.001 on a 0100 scale), neuropsychological performance (1 pathological task, P0.002) and total bone mineral density (0.03 g/cm(2), P0.026). There were no significant changes in CD4 cell count, bilirubin, atazanavir plasma levels, adherence and body fat distribution over time. Simplification to atazanavir/ritonavirlamivudine was apparently safe and associated with rare virological failure, without resistance selection. This strategy deserves further investigation in a randomized trial.