Objectives: To evaluate the efficacy and safety of switching from boosted lopinavir (LPV/r) to boosted atazanavir (ATV/r) in virologically suppressed HIV-1-infected patients versus continuing LPV/r.
Methods: Forty-eight weeks analysis of a randomized, open-label, noninferiority trial including patients with virological suppression (< or = 200 copies/mL for > or = 6 months) on LPV/r-containing triple highly active antiretroviral therapy. Patients (n = 248) were randomized 1:1 either to continue LPV/r twice a day (n = 127) or to switch to ATV/r every day (ATV/r; n = 121), with no change in nucleoside reverse transcriptase inhibitor backbone. Those known to have >4 protease inhibitor (PI)-associated mutations and/or who had failed >2 PI-containing regimens were excluded.
Results: Baseline characteristics were balanced. 30% harboured > or = 1 PI-associated mutation (10% harboured > or = 1 major mutation). Treatment failure at 48 weeks (primary end point) occurred in 20% (25 of 127) of the LPV/r arm and in 17% (21 of 121) of the ATV/r arm (difference -2.3%; 95% confidence interval: -12.0 to 8.0; P = 0.0018). Virological failure occurred in 7% (9 of 127) of the LPV/r arm and in 5% (6 of 121) of the ATV/r arm (difference -2.1%; 95% confidence interval: -8.7% to 4.2%, P < 0.0001 for noninferiorating). CD4 changes from baseline were similar in each arm (approximately 40 cells/mm). Adverse event rate leading to study drug discontinuation was 5% in both arms. Median fasting triglycerides and total cholesterol decreased significantly in the ATV/r arm (-53 and -19 mg/dL, respectively versus -4 and -4 mg/dL in the LPV/r arm; P < 0.001 in both comparisons). Alanine aminotransferase/aspartate aminotransferase hepatic abnormalities were similar in the 2 arms.
Conclusions: Switching to ATV/r in virologically suppressed patients who were receiving a LPV/r-containing highly active antiretroviral therapy provided comparable (noninferior) efficacy and a safety profile with improved lipid parameters [ISRCTN24813210].