Comparison of PI vs PI  ATV vs ATV/r BMS 089  LPV/r mono vs LPV/r + ZDV/3TCMONARK  LPV/r QD vs BIDM M A5073  LPV/r + 3TC vs LPV/r + 2 NRTIGARDEL  ATV/r vs FPV/rALERT  ATV/r vs DRV/rATADAR  FPV/r vs LPV/rKLEAN  SQV/r vs LPV/rGEMINI  ATV/r vs LPV/rCASTLE  DRV/r vs LPV/rARTEMIS

ALERT Study: ATV/r QD vs FPV/r QD, in combination with TDF/FTC  Design Smith KY. AIDS ResTher 2008;5:5  Objective  Primary endpoint: HIV RNA < 50 c/mL at W48 –No power calculation due to limited sample size Note: FPV/r and TDF/FTC were administered with or without food; ATV/r with food Substitution of ABC/3TC fdc for TDF/FTC was allowed *Randomisation was stratified on HIV RNA 100,000 c/mL ALERT Adults > 18 years ARV-naïve or < 14 days prior ART HIV RNA > 1,000 c/mL Any CD4 cell count N = 53 Randomisation* 1:1 Open-label FPV/r 1400/100 mg QD + TDF/FTC fdc QD ATV/r 300/100 mg QD + TDF/FTC fdc QD

FPV/r N = 53 ATV/r N = 53 Median age, years40 Female21%11% White/Black/Other64% / 34% / 2%49% / 45% / 6% HIV RNA (log 10 c/mL), median HIV RNA > 100,000 c/mL45% CD4 cell count (/mm 3 ), median CDC class C17%21% Discontinuation before W48, n (%)8 (15%)4 (8%) For adverse event11 For virologic failure4 *3 Baseline characteristics and patient disposition ALERT Study: ATV/r QD vs FPV/r QD, in combination with TDF/FTC Smith KY. AIDS ResTher 2008;5:5 * In 2 of the 4 patients, detection at baseline of pre-existing resistance to FPV or TDF/FTC ALERT

Outcome at week 48 ALERT Study: ATV/r QD vs FPV/r QD, in combination with TDF/FTC Smith KY. AIDS ResTher 2008;5:5 M/D = F : Missing/Discontinuation equals Failure ALERT Mean CD4 increase at W48: 170/mm 3 (FPV/r) vs 183/mm 3 (ATV/r) (p = 0.4) ITT, M/D = FObserved data FPV/r ATV/r % HIV RNA < 50 c/mLSafety  Diarrhoea and nausea were more frequent in the FPV/r  Grade 3-4 hyperbilirubinemia in ATV/r group = 28%  GFR decline > 25% was similar in both groups; TDF/FTC was discontinued in 3 patients (FPV/r group) for GFR decrease to < 50 mL/min  Median changes in total cholesterol, LDL- cholesterol and HDL-cholesterol were similar in both groups; triglycerides increase was higher in the FPV/r group; use of lipid-lowering agents: FPV/r = 7 vs ATV/r = 1

ALERT Study: ATV/r QD vs FPV/r QD, in combination with TDF/FTC  Summary - Conclusion –Similar virologic and immunologic outcome at W48 with FPV/r 1400/100 mg QD and ATV/r 300/100 mg QD, in combination with TDF/FTC fdc –Higher gastrointestinal intolerance with FPV/r –High incidence of increased bilirubin with ATV/r –Higher triglycerides increase with FPV/r; total, HDL- and LDL- cholesterol changes similar in both groups –Limitation: small size of the study Smith KY. AIDS ResTher 2008;5:5 ALERT