Metabolic effects of atazanavir/ritonavir vs darunavir/ritonavir in combination with tenofovir/emtricitabine in antiretroviral‐naïve patients (ATADAR Study)

Abstract

Purpose of the studyATV/r or DRV/r plus TDF/FTC are recommended for first‐line therapy due at least in part to their clinical tolerability and scarce metabolic effects. We investigated whether both regimens might differ regarding plasma lipids, insulin resistance (HOMA‐IR), and estimated glomerular filtration rate (MDRD).MethodsMulticentre, randomized, clinical trial (ATADAR Study, NCT01274780). Primary end‐point: 24‐week change in total cholesterol. Secondary end‐points: changes in lipids other than total cholesterol, HOMA‐IR, and MDRD; clinical tolerability; and efficacy. We assumed that patients assigned to DRV/r would have an increase in plasma total cholesterol<21 mg/dL, which was the difference between lopinavir/r and ATV/r in CASTLE study. Fasting plasma lipids, glucose, insulin, and creatinine were measured at baseline, and 4, 12, and 24 weeks. Analyses were by intent‐to‐treat.Summary of results180 patients were randomized (ATV/r=91, DRV/r=89), 95% Caucasian, and 8% co‐infected with hepatitis C virus. At baseline (mean, SD): age 36 (9) years; plasma log HIV RNA 4.8 (0.7); CD4 334 (189) cells/mm3; triglycerides 107 (62), total cholesterol 158 (32), LDL cholesterol 97 (28), HDL cholesterol 39 (11) mg/dL, and glucose 84 (13) mg/dL; HOMA‐IR 2.47 (3.46); and MDRD 108 (21) mL/min/1.73 m2. At 24 weeks, total cholesterol (mean, SD) changed +7.26 (26.76) mg/dL with ATV/r and +11.47 (25.85) mg/dL with DRV/r (estimated difference ATV/r minus DRV/r −4.21 (95% CI−12.11 to +3.69), P=0.2944), thus confirming our primary hypothesis. Changes (mean, SD) in triglycerides were roughly similar: +16.29 (61.76) mg/dL with ATV/r and +18.40 (64.24) mg/dL with DRV/r (P=0.8261), but there were trends to more favourable changes in LDL (−2.14 [21.45] vs +3.14 [21.97] mg/dL, P=0.1160) and HDL cholesterol (+5.50 [10.36] vs +3.88 [8.42] mg/dL, P=0.2625), and total‐to‐HDL cholesterol ratio (−1.16 [6.38] vs −0.14 [0.86], P=0.0652) with ATV/r than with DRV/r. There were small, non‐significant decreases in HOMA‐IR (ATV/r −0.17 [2.48] vs DRV/r −0.70 [3.38], P=0.3785) and MDRD (ATV/r −7 [22] vs DRV/r −6 [15] mL/min/1.73 m2, P=0.6652). 6 ATV/r and 3 DRV/r patients had their study drugs discontinued because of adverse effects (P=0.4967). 7 additional patients in each arm had confirmed HIV RNA >50 copies.ConclusionsThere were trends to more favourable changes in LDL and HDL cholesterol and particularly total‐to‐HDL cholesterol ratio at 24 weeks with ATV/r than with DRV/r.