1.  Design Open-label 18-70 years Chronic HCV infection Genotype 1 HCV RNA > 10,000 IU/mL HIV co-infection Stable ART* with HIV RNA < 50 c/mL ≥ 24 weeks CD4 ≥ 300/mm 3 if on ART, > 500/mm 3 if no ART N = 53 W24W48 C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87 SMV + PEG-IFN + RBV W12 SMV 150 mg : 1 pill qd ; PEG-IFN  -2a : 180  g SC once weekly RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) Response-guided therapy : Patients with HCV RNA < 25 IU/ml at W4 and < 15 IU/ml at W12 stopped treatment at W24, otherwise they continued until W48 Virological stopping rules : SMV discontinued if HCV RNA >1000 IU/mL at W4 or W12, or if HCV RNA confirmed ≥ 25 IU/mL at W24 or W36 Naïve or prior relapse Partial or null response or cirrhosis * Permitted ART : 3TC/FTC, ABC, TDF, RPV, RAL, MVC  Objective : SVR 12 (HCV RNA < 25 IU/mL) by intention to treat

2. Naïve N = 53 Prior relapse N = 15 Prior Partial response N = 10 Prior null response N = 28 Median age, years48494847 Female9%33%10%18% White / Black76% / 19%80% / 13%90% / 10%93% / 7% Genotype 1a / 1b79% / 19%80% / 20%90% / 10%86% / 14% Baseline HCV RNA, log 10 IU/ML, median6.576.456.226.49 Metavir score F3-F421%18%60%59% IL28B genotype CC29%47%10%18% HIV treatment at baseline81%100%90%93% RAL / RPV / MVC, %79 / 23 / 587 / 20 / 089 / 11 / 0100 / 0 / 4 Discontinued study, n (%) Adverse event Lost to follow-up Non-compliance Other 4021140211 01010010100 4110241102 Baseline characteristics and patient disposition C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87

3. SVR 12 (HCV RNA < 25 IU/mL) 25 50 100 75 74 % 70 72 N 106 89 57 AllNaïve 79 87 67 RelapseNull 5315305818 71 Partial 88  Response guided therapy (RGT) : –Patients with HCV RNA < 25 IU/ml at W4 (undetectable or detectable) and <15 IU/ml at W12 (undetectable) stopped treatment after W24 –Of the 54 (58%) patients who met RGT, 87% had SVR 12 Treatment-experienced GT 1b GT 1a All GT 1a Q80K+ GT 1a Q80K- C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87 0 1028

4. SVR 12 (HCV RNA < 25 IU/mL) C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87 Metavir F0-F2Metavir F3-F4 25 50 100 75 80 % 78 64 57 60 57 89 67 50 100 N45922277223710 OverallNaïveRelapseNullPartial Treatment-experienced 0

5. SVR 12 (HCV RNA < 25 IU/mL) IL28B CCIL28B non-CC C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87 25 50 100 75 96 % 100 66 Overall 80 52 73 100 NaïveRelapseNullPartial Treatment-experienced 67 100 0 N287771537619523

6.  Emergence of resistance – Paired baseline and failure NS3 sequencing in 26/29 failure – Emergence of NS3 mutations in 25/26 (96%)  HIV endpoints –Confirmed failure : 2/93 (2.2%) of patients on antiretroviral therapy ; both had SVR 12  Virologic failure NaïvePrior partial respondersPrior null responders On-treatment failure5 (9.4%)2 (20%)11 (39%) Viral breakthrough3 (5.8%)1 (10%)8 (27%) Relapse5 (10.4%)-2 (12%) C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87

7. All patients N = 106 Discontinuation due to adverse event5 (4.7%) Grade 3 AE27.4% Grade 4 AE6% Fatigue41% Headache28% Nausea26% Neutropenia28% Anemia21% Pruritus20% Rash16% Sunburn3% Photosensitivity2% Total bilirubin increase5% Adverse events C-212 C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection Dieterich D. CID 2014;59:1579-87

8. C-212 Study: SMV + PEG-IFN + RBV for genotype 1 in HIV co-infection  Summary –Oral, once-daily treatment with SMV 150 mg for 12 weeks plus PEG-IFN + RBV for either 24 or 48 weeks led to high rates of SVR 12 in patients with HCV genotype 1 and HIV-1 coinfection, regardless of prior HCV treatment response –Most eligible patients met response-guided therapy criteria enabling a shorter, 24-week overall duration of PEG-IFN + RBV therapy –SMV was generally well tolerated, with safety similar to that reported in larger studies in patients without HIV coinfection –Limitations No control arm C-212 Dieterich D. CID 2014;59:1579-87