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Until now, few prospective data have been published on ritonavir-boosted atazanavir as initial therapy. This industry-sponsored, phase III, open-label trial compares ritonavir-boosted atazanavir with twice-daily lopinavir/ritonavir.
A total of 883 treatment-naive HIV-infected patients were randomized to receive ritonavir-boosted atazanavir (300 mg, with 100 mg of ritonavir, once daily) or lopinavir/r (400/100 mg twice daily in the older soft-gel formulation). All patients also received once-daily tenofovir/FTC. The population (31% women) had a median age of 35, a median viral load of 4.98 log copies/mL, and a median CD4 count of 205 cells/mm3; study groups were well matched.
At week 48, 78% of the ritonavir-boosted atazanavir group and 76% of the lopinavir/r group had viral loads <50 copies/mL, meeting the study-specified criterion for noninferiority. Treatment responses remained similar between arms whether the baseline viral load was less than or greater than 100,000 copies/mL. In a post hoc analysis, patients with lower baseline CD4-cell counts appeared to have diminished 48-week responses to lopinavir/r (P=0.0085) but not to ritonavir-boosted atazanavir (P=0.51); this difference might reflect the lopinavir/r group’s higher rate of discontinuation because of adverse events at CD4 counts <50 copies/mm3.
Gastrointestinal side effects were more common with lopinavir/r than with ritonavir-boosted atazanavir. About one third of patients receiving ritonavir-boosted atazanavir had bilirubin levels ≥2.6 times the upper limit of normal. Discontinuations for adverse events were infrequent in both arms (10 for ritonavir-boosted atazanavir [3 because of jaundice] and 14 for lopinavir/r). Total cholesterol, non-HDL cholesterol, and triglyceride levels increased more with lopinavir/r than with ritonavir-boosted atazanavir, and a higher proportion of the lopinavir/r group required lipid-lowering therapy (8%, vs. 2% of the ritonavir-boosted atazanavir group). Two patients on ritonavir-boosted atazanavir (but none in the lopinavir/r group) developed nonpolymorphic PI-related mutations.
Molina J-M et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet 2008 Aug 23; 372:646. (http://www.thelancet.com/journals/lancet/article/PIIS0140673608610818/)
Comment
Even before this study was presented at the 2008 Retrovirus Conference (AIDS Clin Care Mar 10 2008), ritonavir-boosted atazanavir with tenofovir/FTC was being used extensively in treatment-naive patients because of its low pill burden (3 pills daily — 1 each for atazanavir, ritonavir, and coformulated tenofovir/FTC), its low rate of gastrointestinal toxicity, and its relatively neutral effect on lipids. This comparative trial provides reassurance that the safety and efficacy of ritonavir-boosted atazanavir are comparable to those of lopinavir/r. Now, we eagerly await the planned comparative trials of ritonavir-boosted atazanavir and ritonavir-boosted darunavir, another PI that has recently shown favorable results as initial therapy (AIDS Clin Care Aug 11 2008).