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

Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD Gathe J. JAIDS 2009;50: W48W96W8 M patients > 18 years ARV-naïve HIV RNA > 1,000 c/mL N = 167 N = 166 Randomisation 1:1:1:1 Open-label  Design N = 165 LPV/r tablet QD + TDF + FTC LPV/r SGC QD + TDF + FTC LPV/r tablet BID + TDF + FTC LPV/r SGC BID + TDF + FTC N = 166 LPV/r tablet QD + TDF + FTC N = 333 LPV/r tablet BID + TDF + FTC N = 331  Objective –Primary endpoint: HIV RNA < 50 c/mL at W48 (ITT, NC = F) –Non-inferiority of LPV/r QD vs BID if lower margin of the 95% CI for the difference = - 12% (> 90% power) LPV/r dose: 400/100 mg BID or 800/200 mg QD

Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD LPV/r QDLPV/r BID Randomized, N Treated eligible patients, N Mean age, years Female20.1%23.3% White/Black78% / 17%73% / 20% HIV RNA (log 10 c/mL), mean (p = 0.02 vs QD) HIV RNA > 100,000 c/mL48%58.3% (p = vs QD) CD4 cell count (/mm 3 ), mean CD4 < 200/mm 3 45%46% Discontinuation by W48, N (%)49 (15%)55 (17%) For adverse event1610 For virologic failure25 Lost to follow-up/withdrew consent/ non adherence/death 10/16/ 5/2 17/13/ 9/1 Patient disposition and baseline characteristics M Gathe J. JAIDS 2009;50:474-81

Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD Response to treatment at week 48 M QD (N = 333) BID (N = 331) ITT, NC = FObserved data Primary efficacy endpoint % % CI for the difference = - 5; 8 95% CI for the difference = - 8; 3  Mean CD4 increase at W48: 186/mm 3 (QD) vs 198/mm 3 (BID) (p = 0.32)  Sensitivity ITT, NC = F, analysis adjusting for baseline imbalance in HIV RNA level confirms non inferiority of virologic response (95% CI for the difference = - 6; 7)  Sub-group post hoc analyses: –% HIV RNA 100,000 c/mL) or CD4 count ( 200/mm 3 ) –for patients with baseline HIV RNA > 100,000 c/mL and CD4 < 200/mm 3, HIV RNA < 50 c/ml = 74% QD vs 73 % BID Gathe J. JAIDS 2009;50:474-81

Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD  During the first 8 weeks of treatment –Clinical (gastrointestinal) and laboratory (lipids) tolerability similar for SGC and tablets  Resistance –Among 17 subjects (10 QD and 7 BID) tested for resistance (HIV RNA > 50 c/mL at or after W24 and confirmed > 400 c/mL within 4 weeks): no emergence of PI or TDF resistance mutations. M184V emergence in 3 patients (2 QD, 1 BID) Adverse events and resistance LPV/r QD (N = 333)LPV/r BID (N = 331)p Adverse events of at least moderate severity related to study drugs Diarrhoea17%15%NS Nausea7%5%NS Vomiting3%4%NS Grade 3/4 laboratory abnormalities AST > 5 x ULN1%2%NS Cholesterol > 300 mg/dL4%3%NS Triglycerides > 750 mg/dL3%6%0.063 Creatinine clearance < 50 mL/min2% NS M Gathe J. JAIDS 2009;50:474-81

Study M05-730: LPV/r QD vs BID, in combination with TDF + FTC QD  Summary - Conclusion –In antiretroviral-naïve adults, LPV/r QD was virologically non inferior at W48 to LPV/r BID, when administered in combination with TDF and FTC –During the first 48 weeks of therapy, there were no significant differences in the safety or tolerability of QD vs BID LPV/r –This study used LPV/r tablets, and did not show differences in rate of diarrhoea between QD and BID dosing –In subgroups with high baseline HIV RNA and/or low CD4 count, efficacy of LPV/r QD and BID was similar –Absence of resistance emergence to LPV/r or TDF, in either groups –Limited and similar lipid impact of both LPV/r dosing –Patient preference of the tablet over the soft-gel capsule –Results support the use of LPV/r QD in combination with TDF and FTC in antiretroviral-naive patients M Gathe J. JAIDS 2009;50:474-81