Comparison of PI vs PI ATV vs ATV/r BMS 089 ARV-trial.com Comparison of PI vs PI ATV vs ATV/r BMS 089 LPV/r mono vs LPV/r + ZDV/3TC MONARK LPV/r QD vs BID M02-418 M05-730 A5073 LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL ATV/r vs FPV/r ALERT ATV/r vs DRV/r ATADAR FPV/r vs LPV/r KLEAN SQV/r vs LPV/r GEMINI ATV/r vs LPV/r CASTLE DRV/r vs LPV/r ARTEMIS 1

ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) ARV-trial.com ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) Design Randomisation* Open-label N = 161 LPV/r 800/200 mg QD + FTC 200 mg + (d4T-XR or TDF) QD HIV-infected patients > 13 years ARV-naïve or < 7 days prior ART HIV RNA > 2,000 c/mL Any CD4 cell count N = 159 LPV/r 400/100 mg BID + FTC 200 mg + (d4T-XR or TDF) QD *Randomisation was stratified on HIV RNA < 100,000 c/mL or > 100,000 c/mL The study had a third arm of LPV/r QD + FTC + (d4T-XR or TDF) administered by DOT in 82 patients, not included in the comparison of the 2 other arms. Objective Primary endpoint: Kaplan-Meier of sustained virologic response at W48 Sustained virologic response = lack of confirmed HIV RNA > 200 c/mL at W48 after confirmed HIV RNA < 200 c/ml ; or lack of confirmed HIV RNA > 200 c/mL at or after W24 ; lack of HIV RNA > 200 c/mL at W48 (no confirmation required) Width of < 0.2 for the 2-sided 95% CI for the difference in probability of SVR A5073 Flexner C. CID 2010; 50:1041-52 2

ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) ARV-trial.com ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) Patient disposition and baseline characteristics LPV/r QD LPV/r BID Mean age, years 39.3 38.2 Female 21% 23% White/Black/Other 34% / 32% / 34% 27% / 36% / 37% NRTI : d4T-XR / TDF* 62% / 38% 60% / 40% HIV RNA (log10 c/mL), median 4.8 4.9 HIV RNA > 100,000 c/mL 51% 52% CD4 cell count (/mm3), median 218 194 CD4 < 200/mm3 47% 53% HCV Ab+ 13% Discontinuation before W48, n (%) 52 (32%) 41 (26%) For toxicity 17 10 Virologic failure 36 29 * d4T-XR : 100 mg ; TDF : 300 mg Note: LPV/r was administered as soft-gel capsules A5073 Flexner C. CID 2010; 50:1041-52 3

ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) ARV-trial.com ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) Estimated probability of sustained virologic response (95% CI) at W48 LPV/r QD LPV/r BID Difference BID-QD Intent-to treat Overall 0.78 (0.70-0.84) 0.81 (0.73-0.86) 0.03 (-0.07 ; 0.12) HIV RNA < 100,000 c/mL 0.80 (0.69-0.88) 0.72 (0.59-0.81) - 0.09 (- 0.23 ; 0.06) HIV RNA > 100,000 c/mL 0.76 (0.64-0.84) 0.89 (0.79-0.94) 0.13 (0.01 ; 0.25) As-treated 0.85 (0.78-0.90) 0.00 (-0.09 ; 0.09) 0.86 (0.75-0.93) 0.80 (0.67-0.88) -0.07 (-0.20 ; 0.07) 0.84 (0.73-0.91) 0.90 (0.80-0.95) 0.06 (-0.06 ; 0.17) Regimen Completion* 0.61 (0.53-0.68) 0.66 (0.58-0.73) 0.05 (-0.05 ; 0.16) * Virologic failure or discontinuation of initially randomised LPV/r schedule, whichever occurred first. No difference between groups, both overall and in each screening HIV RNA level stratum A5073 Flexner C. CID 2010; 50:1041-52 4

ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) ARV-trial.com ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF) Emergence of resistance mutations to PI in virologic failure Low incidence and no difference between QD (2/35 failure) and BID (3/26 failure) Grade 3 or 4 clinical events and laboratory abnormalities No significant difference in time to event between QD and BID Adherence (electronic monitoring) Significantly higher with QD during the first 24 weeks and between W24 and W48 Lopinavir Ctrough at week 16 and week 48 Significantly lower and more variable with QD At W48, median Ctrough : 3.4 mg/mL for QD vs 5.6 mg/mL for BID Conclusion Overall, LPV/r QD and BID had similar outcomes Patients with HIV RNA levels > 100,000 c/mL had better virologic response with LPV/r BID A5073 Flexner C. CID 2010; 50:1041-52 5