ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label.

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ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Randomisation 1 : 1 Open-label W12 W24 Design 18-70 years HCV genotype 1 HCV RNA ≥ 10,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV HIV infection, on ATV/r or RAL (Part 1a) or DRV/r (Part 1b) HIV RNA < 40 c/ml and CD4 ≥ 200/mm3 Cirrhosis Child-Pugh A allowed No HBV co-infection N = 31 OBV/PTV/r + DSV + RBV Part 1a * OBV/PTV/r + DSV + RBV N = 32 N = 10 ** Part 1b OBV/PTV/r + DSV + RBV OBV/PTV/r + DSV + RBV N = 12 *** * Randomisation stratified on prior PEG-IFN + RBV therapy, and cirrhosis ; naïve patients also stratified on IL-28B (CC vs non-CC); experienced patients also stratified on prior response (null, partial, relapse) ** DRV 800 mg qd (ritonavir stopped) ; *** DRV 600 mg bid + ritonavir 100 mg qd Treatment regimens Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg qd = 2 tablets Dasabuvir (DSV) : 250 mg bid RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) Primary efficacy endpoint SVR12 (HCV RNA < 25 IU/ml), with 2-sided 95% CI, comparison between groups TURQUOISE-I Sulkowski MS, JAMA 2015;315:1223-31 ; Wyles D. J Infect Di 2017; 215:599-605 1

Baseline characteristics and patient disposition (Part 1a) ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Baseline characteristics and patient disposition (Part 1a) 12 weeks N = 31 24 weeks N = 32 Mean age, years 50.9 Female 6% 9% Body mass index, mean 26.4 27.2 Genotype : 1a / 1b 87% / 13% 91% / 9% IL28B non-CC genotype 84 % 78 % HCV RNA log10 IU/ml, mean (SD) 6.54 ± 0.57 6.60 ± 0.78 Fibrosis score F0-F1 / F2 / F3 / F4 (%) 52 / 16 / 13 / 19 63 / 16 / 3 / 19 Prior treatment with PEG-IFN + RBV, N (%) 11 (35%) 10 (31%) Null response 5 Partial response 2 Relapse 1 3 CD4/mm3, mean 633 625 ARV regimen : ATV/r / RAL 52% / 48% 38% / 63% Discontinued treatment, N (withdrew consent) (virologic breakthrough) TURQUOISE-I Sulkowski MS, JAMA 2015;315:1223-31 2

Virologic Outcome (Part 1a) 1 virologic breakthrough ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Virologic Outcome (Part 1a) 12 weeks N = 31 24 weeks N = 32 SVR12 (HCV RNA < 25 IU/ml) 94% (95% CI: 79 - 98) 91 % (95% CI : 76 - 97) Failure*, N Reasons 2 1 consent withdrawn 1 relapse 3 1 virologic breakthrough 2 re-infection Mutations detected Relapse NS3 : D168V NS5A : M28T NS5B : S556G Breakthrough NS3 : R155K NS5A : Q30R Prior PEG-IFN + RBV therapy in failures Naïve = 1, Null response = 1 Naïve = 2, Null response = 1 Fibrosis stage in failures F3 / F4 F4 / F0-F1 / F0-F1 * All 5 = genotype 1a No HIV RNA failure (3 blips in W12-group and 5 blips in W24-group) Decrease in absolute but not relative CD4 cell counts TURQUOISE-I Sulkowski MS, JAMA 2015;315:1223-31 3

Adverse events, Part 1 a, n (%) TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Adverse events, Part 1 a, n (%) 12 weeks, N = 31 24 weeks, N = 32 AE leading to treatment discontinuation AE leading to RBV dose reduction 5 6 Serious adverse event AE occurring in > 10% in either group Fatigue 58% 38% Insomnia 16% 22% Nausea 19% Headache 13% Upper respiratory tract infection Pruritus 6% Cough 7% Ocular icterus 3% Diarrhea Hyperbilrubinemia ALT > 5 x ULN / AST > 5 x ULN 0 / 0 0 / 1 Total bilirubin > 3 x ULN 35% TURQUOISE-I Sulkowski MS, JAMA 2015;315:1223-31

Baseline characteristics and SVR12 (Part 1b) ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Baseline characteristics and SVR12 (Part 1b) OBV/PTV/r + DSV + RBV DRV qd, n = 10 DRV bid, n = 12 Median age, years 56 53 Female, % 20 25 Body mass index, median 26 Genotype 1a, % 90 50 IL28B non-CC genotype, % 100 83 Cirrhosis, % Prior treatment with PEG-IFN + RBV, % 30 DRV as first PI, % 33 CD4/mm3, median 656 612 SVR12 100% HIV RNA blips : 2/10 DRV qd and 3/12 DRV bid TURQUOISE-I Wyles D. Journal Infect Dis 2017 (ePub ahead of print) 5

Pharmacokinetic parameters of DRV qd and bid (Part 1b) ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Pharmacokinetic parameters of DRV qd and bid (Part 1b) OBV/PTV/r + DSV + RBV DRV qd, n = 10 DRV bid, n = 12 Cmax 0.924 0.921 AUC 0.833 0.876 Ctrough 0.643 0.730 Values are the least square mean ratios (90% confidence intervals) for DRV pharmacokinetic parameters with and without OBV/PTV/r + DSV (DRV + OBV/PTV/r + DSV vs DRV alone) TURQUOISE-I Wyles D. J Infect Di 2017; 215:599-605 6

1 (colitis and dehydration, not related to study drugs) TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Adverse events, Part 1 b, n OBV/PTV/r + DSV + RBV DRV qd, n = 10 DRV bid, n = 12 AE leading to treatment discontinuation Serious adverse event 1 (colitis and dehydration, not related to study drugs) AE occurring in > 15% in either group Fatigue 4 Hemoglobin decreased 1 Irritability 3 2 Nausea ALT > 5 x ULN / AST > 5 x ULN 0 / 0 Total bilirubin > 3 x ULN Hemoglobin 8-10 g/dl, < 8 g/dl 1 / 0 3 / 1 RBV dose reduction, n = 9 (decrease hemoglobin levels, n = 4 ; anemia, n = 3 ; fatigue, n = 2) TURQUOISE-I Wyles D. J Infect Di 2017; 215:599-605

ARV-trial.com TURQUOISE-I Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + ribavirin for HCV in HIV co-infected patients Summary In Part 1a of this open-label, randomised uncontrolled study, treatment with the all-oral, IFN-free 3D plus ribavirin regimen resulted in high SVR12 rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks No discontinuation for AE The 2 failures (1 virologic breakthrough and 1 relapse) were observed in patients with genotype 1a and F4 fibrosis Limitations Small sample size ARV therapy limited to ATV/r- or RAL-containing regimens Role of RBV not addressed In Part 1b, HCV genotype 1 HIV-1 coinfected patients on stable DRV-containing ART achieved 100% SVR12 while maintaining plasma HIV-1 RNA suppression. Despite DRV Ctrough decrease, episodes of intermittent HIV-1 viremia were infrequent TURQUOISE-I Sulkowski MS, JAMA 2015;315:1223-31 ; Wyles D. J Infect Di 2017; 215:599-605 8