Switch to ATV ± r-containing regimen  SWAN Study  SLOAT Study

SLOAT Study: switch LPV/r to ATV+r  Design  Objective  Non inferiority in the proportion of patients with virologic rebound at W48 (upper limit of the 95% CI for the difference = 90%, 90% power)  Virologic rebound: HIV-1 RNA > 50 c/mL Switch to ATV+r qd* + continue NRTIs Continue LPV/r + NRTIs * ATV 400 mg (N = 49), or ATV/r 300/100 mg if TDF part of NRTI backbone (N = 53) Randomisation Open-label 224 HIV+ patients On LPV/r + 2 NRTIs ≥ 3 months HIV RNA < 50 c/mL ≥ 24 weeks N = 87 N = 102 W48 Soriano V, JAC 2008;61:200-5 SLOAT

SLOAT Study: switch LPV/r to ATV+r LPV/r N = 87 ATV+r N = 102 Median age, years4042 Female41%18% Median CD4 cell count/mm Median exposure to prior ARV, months*3857 Chronic Hepatitis C45%36% Chronic hepatitis B3% Discontinuation before W48, n1 (lost to follow-up)2 (jaundice) Baseline characteristics and patient disposition * Nearly half of the patients had been exposed to other PIs, before LPV/r, and failure on prior PIs had occurred in two-thirds of these PI-experienced patients Soriano V, JAC 2008;61:200-5 SLOAT

SLOAT Study: switch LPV/r to ATV+r Virologic failure /1029/87 % Results: W48 outcome  Resistance mutations at virologic failure –LPV/r: 1/9 –ATV: 2/5 –ATV/r: 3/7  Median ATV C trough * –ATV/r:0.822 mg/L –ATV:0.234 mg/L  Median CD4 increase between baseline and W48 –LPV/r:46/mm 3 –ATV+r:42/mm 3 Soriano V, JAC 2008;61:200-5 SLOAT Switch to ATV±r Continue on LPV/r * Effective minimal C trough = 0.15 mg/L

SLOAT Study: switch LPV/r to ATV+r Median changes (mg/dL) in fasting metabolic parameters from baseline up to Week 48 LPV/r N = 87 ATV total N = 102 p ATV 400 N = 49 p ATV/r 300/100 N = 53 p Triglycerides-5-80< < Total cholesterol < < NS HDL cholesterol-0.5+2NSNS+4NS LDL cholesterol+1 NS-4NS+2NS Glucose+6NS-2NS+1NS Proportion of patients with LDL cholesterol levels within NCEP categories LDL mg/dL21%7% LDL mg/dL9%3% LDL ≥ 190 mg/dL5%1% Metabolic parameters Soriano V, JAC 2008;61:200-5 SLOAT Use of lipid-lowering agents was more frequent in the LPV/r group: 17% vs 5% (p = 0.006)

SLOAT Study: switch LPV/r to ATV+r  Conclusion –For patients with undetectable viraemia on a stable LPV/r-based regimen, replacement of LPV/r by ATV+r may provide: An overall reduction in fasting cholesterol and triglycerides No increased risk of virologic failure Soriano V, JAC 2008;61:200-5 SLOAT