Switch to DRVr reduced dose DRV 600 DRV

Switch to DRV/r reduced dose § DRV 600

DRV 600 Study: switch to DRV/r 600/100 mg § Design Randomisation* 1: 1 Open-label N = 50 ≥ 18 years Stable DRV/r 800/100 mg + 2 NRTI with HIV RNA < 50 c/m. L > 12 weeks No previous virologic failure on PI No resistance mutations to DRV W 48 DRV 800 mg + rtv 100 mg + 2 NRTI (continuation) DRV 600 mg + rtv 100 mg + 2 NRTI N = 50 * Randomisation was stratified on HIV RNA (≤ or > 100, 000 c/m. L) prior to ART start § Objective – – DRV 600 Primary Endpoint : proportion with treatment success at W 48 (ITT analysis) • Assuming 90% efficacy at W 48, sample size of 100 provide 80% power to detect a minimum difference of 15% in efficacy Other endpoints : observed analysis of virologic efficacy, PK substudy, cost-efficacy analysis Molto J. J Antimicrob. Chemother 2015; 70: 1139 -45

DRV 600 Study: switch to DRV/r 600/100 mg Baseline characteristics and disposition DRV/r 800/100 N = 50 DRV/r 600/100 N = 50 45 46 Female 18% 20% HCV co-infection 14% 26% Baseline CD 4/mm 3, mean 591 523 Nadir CD 4/mm 3, mean 201 197 Duration of HIV RNA < 50 c/m. L (weeks), median 107 NRTI backbone TDF/FTC ABC/3 TC 68% 32% 64% 3 5 Confirmed HIV RNA > 50 c/m. L 2 3 Lost to follow-up 1 1 Death 0 1 Mean age, years Discontinued at W 48, n DRV 600 Molto J. J Antimicrob. Chemother 2015; 70: 1139 -45

DRV 600 Study: switch to DRV/r 600/100 mg No treatment failure (ITT) DRV/r 800/100 + 2 NRTI 100 % 94 90 Results HIV RNA < 50 c/m. L (observed) DRV/r 600/100 + 2 NRTI 96 Safety 94 80 60 DRV/r 800/100 DRV/r 600/100 Gastrointestinal AE of grade ≥ 2 N=6 N=4 Lipid elevations N=5 0 40 20 No discontinuation for AE 0 Difference - 4% (lower limit -12. 9%) Difference – 2. 2% (lower limit – 9. 6%) Genotype done in 3/5 VF : no emergence of resistance DRV 600 Molto J. J Antimicrob. Chemother 2015; 70: 1139 -45

DRV 600 Study: switch to DRV/r 600/100 mg § Phamacokinetics – Mean DRV Ctrough : 2. 21 ± 1. 44 mg/d. L for DRV/r 800/100 vs : 2. 19 ± 1. 50 mg/d. L for DRV/r 600/100 (p = 0. 94) – No significant difference in AUC nor other PK parameters between the 2 groups Full PK analysis DRV/r 800/100 N = 15 DRV/r 600/100 N = 15 Mean (90%CI) Geometric mean ratio DRV 600/DRV 800(90% CI) 83. 99 (72. 92 – 96. 73 76. 66 (66. 56 – 88. 29) 0. 91 (0. 75 – 1. 10) Cmax (mg/L) 6. 63 (5. 92 – 7. 42) 6. 52 (5. 82 – 7. 29) 0. 98 (0. 84 – 1. 15) Ctrough (mg/L) 1. 84 (1. 45 – 2. 32) 1. 60 (1. 26 – 2. 02) 0. 87 (0. 63 – 1. 21) AUC 0 -24 (mg. h/L) DRV 600 Molto J. J Antimicrob. Chemother 2015; 70: 1139 -45

DRV 600 Study: switch to DRV/r 600/100 mg § Conclusion – The efficacy of a DRV daily dose of 600 mg seemed to be similar to the efficacy of the standard 800 mg dose, in combination with ritonavir 100 mg and 2 NRTI, in virologically suppressed HIVinfected patients switching from therapy with DRV/r 800/100 mg + 2 NRTI – This strategy can potentially translate to substantial savings in the cost of care of HIV-infected patients • Average reduction in annual cost per successfully treated DRV 600 -arm patient of 7273 $US – Limitation : trial not powered to detect differences in efficacy below 15%, which might be clinically relevant DRV 600 Molto J. J Antimicrob. Chemother 2015; 70: 1139 -45