1. Future HCV Treatment Paradigms Mark Sulkowski, MD Professor of Medicine Medical Director, Viral Hepatitis Center Divisions of Infectious Diseases and Gastroenterology/ Hepatology Johns Hopkins Medical Institutions Baltimore Maryland USA

2. Investigational Agents for HCV Interferons Antiviral agents Therapeutic vaccines Host target Replication, polyprotein processing and/or assembly Entry NS5B polymerase Inhibitors NS3 protease inhibitors NS5A replication complex inhibitors 2 miRNA-122 Cyclophilin CYP inhibitors

3. Preclinical Phase I Phase II Phase III Filed Boceprevir (MSD) Telaprevir (Vertex/JJ) TMC-435 (Tibotec/JJ) MK7009 (MSD) ITMN191/R7227 (Roche/Intermune) BI201335 (BI) BMS650032 (BMS) GS9256 (Gilead) MK5172 (MSD) ABT450 (ABT) ACH2684 (Achillion) BMS 790052 (BMS) AZD-7295 (AZN) BMS 824393 (BMS) PPI-1301 EDP-239 (Enanta) GSK Vertex Idenix719 MSD IFN λ Debio 025/ NIM811 (Novartis) Nitazoxamide (Romark) Silibinine Vitamine D BMS BI ROCHE Gilead R7128 (Roche) GS- 7977 Gilead) BI Japan Tobacco R0622 (Roche) Medivir (Tibotec) GLS9393 (GSK) Biocryst INX 189 (Inhibitrex) BMS791325 (BMS) Filibuvir (PFE) GS9190 (Gilead) ANA598 (Anadys) BI201127 (BI) Vx222 (Vertex) ABT333 ABT072 (ABT) IDX 375 (Idenix) IDX 184 (Idenix) SCY-835 PPI-461 VBY-376 VX-985 (Vertex) VX-813 (Vertex) GS9451 (Gilead) RG7348 (Roche) TMC 647055 (Tibotec) A837093 (Abbott) VX-916 VX-759 Celgosivir Bavituximab Direct Acting Antivirals in Development AVL-181 (Avila) AVL-192 (Avila) ACH-2928 (Achillion) GS-5885 Vertex Abbott Nucleoside NS5B Polymerase Inhibitors Nucleotide NS5B Polymerase Inhibitors Non Nuc NS5B Polymerase inhibitors NS3/4A Protease inhibitors NS5A inhibitors DAA combinations Others Cyclophilin. I IDX 077 (Idenix) IDX 079 (Idenix) ABT267 (ABT) Adapted from Bourliere M, et al. Clin Res Hepatol Gastroenterol. 2011;35(suppl 2):S84-S95.

4. Regimens with one DAA + pegIFN alfa/RBV Regimens with two DAAs (± pegIFN alfa and/or RBV) IFN-free Regimens  BI 201335 (PI)  Daclatasvir (NS5A)  Asunaprevir (PI)  GS-7977 (NI)  Simeprevir (TMC-435) (PI)  Alisporivir (CYP)  Vaniprevir (MK-7009, PI)  Daclatasvir + asunaprevir  Sofosbuvir (GS-7977) + RBV  Daclatasvir + asunaprevir  Alisporivir ± RBV Investigational HCV Regimens in Phase 3 New Interferons  Peginterferon-lambda-1a NNI = non-nucleoside NS5B inhibitor, NI = nucleoside NS5B inhibitor, PI = protease inhibitor, RBV = ribavirin, NS5A = replication complex inhibitor Cyp= cyclophilin inhibitor

5. Multiple Combinations Will Emerge Different drugs can contribute variably to each goal. Not all components must be direct-acting antivirals (DAAs). B C Prevention of emergent resistance (pre-existing or de novo) + + A Profound suppression of broad range of viral variants, including pre-existing variants 5

6. INTERFERONS +/- DAA

7. EMERGE: PegIFN lambda-1a vs PegIFN alfa-2a in GT 2/3 HCV Treatment-Naive Pts Interim analysis of randomized, blinded, active-controlled phase IIb trial Zeuzem S, et al. EASL 2012. Abstract 10. Treatment-naive patients infected with genotype 2/3 HCV (N = 118) PegIFN lambda-1a 120 µg/wk + RBV † (n = 29) PegIFN lambda-1a 180 µg/wk + RBV † (n = 29) PegIFN lambda-1a 240 µg/wk + RBV † (n = 30) Wk 24 Genotyping at baseline † RBV dosed at 800 mg/day for genotype 2/3 patients. PegIFN alfa-2a 180 µg/wk + RBV † (n = 30)

8. PegIFN lambda-1a 180 μg dosage chosen for phase III trials EMERGE: Efficacy and Safety Outcomes Zeuzem S, et al. EASL 2012. Abstract 10. SVR24 (%) 0 40 60 80 100 65.5 20 75.9 60.0 53.3 N =29 30 Lambda 120 µg Lambda 180 µg Lambda 240 µg Alfa 180 µg Adverse Event, % Lambda 180 µg (n = 29) Alfa 180 µg (n = 30) Hemoglobin low 3.4 g/dL 6.944.8 RBV dose reduction (Hemoglobin associated) 023.3 Neutrophils low < 750/mm 3 027.6 Platelets low < 100,000/mm 3 024.1 PegIFN dose reduction (hematologic abnormality) 023.3

9. ATOMIC: Sofosbuvir (GS-7977 (NI) + PegIFN/RBV Kowdley KV, et al. EASL 2012. Abstract 1 GS-7977 + PR n=125 n=155 GS-7977 + PR n=52 weeks 0 24 GS-7977 ± RBV RVR 98 97 94 SVR4 92 94 SVR12 NA 90 EOT 99 98 Treatment naïve, mainly Gen1 (few G4/6), non-cirrhotic No S282T mutation seen in 4 relapse pts 12 Viral Response Rates (%)

10. ASPIRE: Simeprevir (PI) + PegIFN/RBV in Treatment Experienced Patients Zeuzem S, et al. EASL 2012. Abstract 2 Simeprevir + P/R weeks 0 48 Treatment experienced, G1, includes cirrhotics PegIFN + RBV 12 n=66 Simeprevir + PegIFN/RBV PegIFN + RBV Simeprevir + PegIFN + RBV 24 n=68 n=66 PegIFN + RBV n=65 100 80 60 40 20 0 85* SVR24 (%) 75* 19 51* 9 37 Relapsers Partial Responders Null Responders * Represents pooled simeprevir duration at 150mg dose

11. Quad Therapy: SVR12 with 16 Weeks of Tegobuvir and GS-9256 plus Peginterferon-alfa 2a and Ribavirin in Treatment-Naïve Genotype 1 HCV Patients Patients with vRVR → 16 or 24 wks Group 1 N = 163 Very rapid virologic response (vRVR) = HCV RNA <LLOQ at Week 2 RVR = HCV RNA <LLOQ at Week 4 PEG + RBV GS-9256 150 mg BID + TGV 20 mg BID + PEG + RBV Day 1 Wk 48Wk 16Wk 24 Response-Guided Therapy SVR12 Nelson DR. EASL 2010. Abstract 12 Per protocol/ completer analysis

12. CYCLOPHILIN INHIBITOR + RBV

13. VITAL-1: Alisporivir-Based Therapy for Trt-Naive GT2/3 Pts Pawlotsky JM, et al. EASL 2012. Abstract 1405. Treatment- naive patients with chronic GT 2/3 HCV infection (N = 340) Alisporivir 1000 mg QD (n = 83) Alisporivir 600 mg QD + RBV (n = 84) Alisporivir 800 mg QD + RBV (n = 94) Wk 24 Stratified by HCV RNA and HCV genotype Alisporivir 600 mg QD + PegIFN (n = 39) PegIFN alfa-2a/RBV (n = 40) All pts received alisporivir loading dose of 600 mg BID during first wk. PegIFN alfa-2a dosed 180 µg/wk. RBV dosed 800 mg/day. Wk 4: RVR assessed Wk 6 24-wk F/U Alisporivir 600 mg QD + PegIFN/RBV Alisporivir 1000 mg QD Alisporivir 600 mg QD + PegIFN/RBV Alisporivir 600 mg QD + RBV Alisporivir 600 mg QD + PegIFN/RBV Alisporivir 800 mg QD + RBV 800 mg/day Alisporivir 600 mg QD + PegIFN/RBV Alisporivir 600 mg QD + PegIFN RVR: No RVR: RVR: No RVR: RVR: No RVR: RVR: No RVR:

14. VITAL-1: SVR12 by Per-Protocol Analysis High SVR rates with alisporivir-based therapy, including IFN-free regimens – However, development of alisporivir currently on hold due to 3 cases of pancreatitis (with 1 death) in > 1800 patients treated to date Pawlotsky JM, et al. EASL 2012. Abstract 1405.. Overall SVR12SVR12 in Pts Receiving IFN-free Therapy SVR12 (%) 0 40 60 80 100 20 ALV1000 81 83 81 77 58 ALV600 RBV ALV800 RBV ALV600 Peg P/R 0 40 60 80 100 20 ALV1000 82 93 91 ALV600 RBV ALV800 RBV 8284933940 n = 172932 n =

15. PI +/- NON-NUCLEOSIDE POLYMERASE INHIBITOR +/- NS5A INHIBITOR +/- RBV

16. Co-Pilot (M12-746) Study: ABT-450/r + ABT-333 Treatment ABT-450/r 250/100 mg QD + ABT-333 400 mg BID + RBV ABT-450/r 250/100 mg QD + ABT-333 400 mg BID + RBV Arm 1 Treatment-naïve (N=19) ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + RBV ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + RBV Arm 2 Treatment-naïve (N=14) ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + RBV ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + RBV Arm 3 Prior P/R non- responders (N=17) 12 Weeks (On Treatment) Follow Up Period Poordad F, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1399.

17. Co-Pilot Study: Demographics and Baseline Characteristics Arm 1 N=19 Arm 2 N=14 Arm 3 N=17 Male, n (%)10 (52.6)14 (100)11 (64.7) White, n (%)15 (78.9)12 (85.7)13 (76.5) Hispanic/Latino, n (%)3 (15.8)04 (23.5) Mean Age ± SD (years)53.6 ± 9.7850.9 ± 10.4552.3 ± 9.03 Mean BMI ± SD (kg/m 2 )27.3 ± 3.8424.6 ± 3.0827.6 ± 4.65 IL28 genotype, n (%) CC CT TT 10 (52.6) 7 (36.8) 2 (10.5) 5 (35.7) 7 (50.0) 2 (14.3) 0 12 (70.6) 5 (26.3) HCV genotype, n (%) 1a 1b 17 (89.5) 2 (10.5) 11 (78.6) 3 (21.4) 16 (94.1) 1 (5.9) HCV RNA Mean ± SD (log 10 IU/mL) >800,000 IU/mL, n (%) 6.25 ± 0.80 14 (73.7) 6.44 ± 1.15 11 (78.6) 6.93 ± 0.47 17 (100) Non-responder status Partial responder Null responder --11 (64.7) 6 (35.3) Poordad F, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1399.

18. Co-Pilot Study: Virologic Results Poordad F, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1399.

19. ABT-267 + PegIFN/RBV in treatment-naïve subjects Results cEVR, complete early virological response; LLOD, lower limit of detection (15 IU/mL); LLOQ, lower limit of quantitation (25 IU/mL); P/R, PegIFN/RBV; SE, standard error; QD, once daily Safety: −ABT-267 had an adverse event profile similar to placebo −No serious adverse events EASL, Barcelona, Spain, 18–22 April 2012; Abstract 1210 66% 100% 86% 75% Week 12 cEVR rates

20. A Randomized, Open Label, Multi-center Study to Evaluate the Antiviral Activity, Safety, and Pharmacokinetics, of ABT-450 With Ritonavir (ABT-450/r) in Combination With ABT-267 and/or ABT-333 With and Without Ribavirin (RBV) in Treatment-Naïve and Null Responder Subjects With Genotype 1 Chronic Hepatitis C Virus Infection N = 560 14 active treatment arms testing combinations of DAAs and RBV – No interferon This study is ongoing, but not recruiting participants ClinicalTrials.gov Identifier: NCT01464827 NCT01464827

21. SOUND-C2: BI 201335 + BI 207127 ± RBV in Trt-Naive GT1 Pts Zeuzem S, et al. EASL 2012. Abstract 101. Treatment-naive pts with GT1 HCV [7% to 17% in each group had cirrhosis] (N = 362) BI 201335 120 mg QD + BI 207127 600 mg TID + RBV (n = 81) BI 201335 120 mg QD + BI 207127 600 mg TID + RBV (n = 80) BI 201335 120 mg QD + BI 207127 600 mg TID + RBV (n = 77) Wk 16 BI 201335 120 mg QD + BI 207127 600 mg BID + RBV (n = 78) BI 201335 120 mg QD + BI 207127 600 mg TID, no RBV (n = 46)* Stratified by HCV subtype and IL28B genotype *Randomization to this arm stopped early due to US FDA concerns regarding lack of RBV. 12-wk follow- up for SVR12 Wk 28 Wk 40 Weight-based RBV dosing (1000-1200 mg/day).

22. SOUND-C2: Higher SVR12 in Pts With GT 1b HCV, IL28B CC, BID Dosing Zeuzem S, et al. EASL 2012. Abstract 101. SVR12 (%) 0 40 60 80 100 20 n/N = 32 75 84 82 1a non-CC 1a CC 1b non-CC 1b CC BID 28wk RBV TID 28wk TID 40wk RBV TID 28wk RBV TID 16wk RBV 32 71 38 71 42 62 32 82 53 0 1a non-CCAll 1b and 1a-CC SVR according to IL28B and HCV subtype: BID28wk + RBV (ITT) SVR according to IL28B and HCV subtype (ITT) 0 40 60 80 100 20 7/22 6/8 31/37 9/11 HCV Subtype and IL28B Genotype

23. 4-Drug Therapy With GS-5885, GS-9451, Tegobuvir, and RBV in Tx-Naive GT1 HCV Interim analysis of randomized phase II study Sulkowski M, et al. EASL 2012. Abstract 1421. Tx-naive patients with chronic GT1 HCV infection (N = 140) GS-5885 30 mg QD + GS-9451 200 mg QD + Tegobuvir 30 mg BID + Ribavirin (n = 46) Randomized 1:2; stratified by HCV RNA (≤ vs > 800,000 IU/mL) and HCV 1 subtype (1a vs 1b) *Patients with HCV RNA ≥ 25 IU/mL at Wk 2 offered rescue therapy including pegIFN or study discontinuation. † Patients rerandomized if HCV RNA < 25 IU/mL at Wks 2-10. GS-5885 90 mg QD + GS-9451 200 mg QD + Tegobuvir 30 mg BID + Ribavirin (n = 94) Wk 2*Wk 12Wk 24 GS-5885 90 mg QD + GS-9451 200 mg QD + Tegobuvir 30 mg BID + Ribavirin Follow-up Rerandomized † Follow-up for SVR24

24. SVR-4 rates among patients with HCV RNA < 25 IU/mL at week 2

25. Effect of IL28B genotype, subtype and NS5A dose on week 2 response and breakthrough

26. Viral breakthrough was associated with resistance to PI, NS5A and NNI

27. Daclatasvir (NS5A) + Asunaprevir (PI) Suzuki F, et al. EASL 2012. Abstract 14 100 80 60 40 20 0 91 SVR24 (%) 9/10 n=21 Weeks 024 Gen1b, non-cirrhotic Daclatasvir + Asunaprevir n=22 64 Null responder IFN intolerant Null responder IFN ineligible and intolerant Among pts with breakthrough (7%) or relapse (9%), low plasma concentrations of DAC and ASU

28. NUCLEOS(T)IDE ANALOGUE POLYMERASE INHIBITOR +/- PI +/- NS5A INHIBITOR +/- RBV

29. I N FORM-SVR: Mericitabine + danoprevir/ritonavir ± RBV in treatment-naïve GT-1: Study design Randomised Phase 2b study of response-guided mericitabine + ritonavir-boosted danoprevir ± RBV in treatment-naive GT-1 HCV patients – n=169: 67% HCV GT-1a; 69% IL28B non-CC Week 24 Week 12 Mericitabine 1000 mg BD + danoprevir/ritonavir 100/100 mg BD + RBV 1000/1200 mg QD Mericitabine + danoprevir/ritonavir + RBV A B a patients with eRVR were re-randomised at Week 12 to maintain or stop treatment b Due to unacceptable relapse rates, re-randomisation was halted and patients in Arm B on active treatment were offered PegIFN/RBV BID, twice daily; eRVR, early rapid virological response; GT, genotype; PegIFN, pegylated interferon; RBV, ribavirin No treatment No eRVR Mericitabine 1000 mg BD + danoprevir/ritonavir 100/100 mg BD + placebo Mericitabine + danoprevir/ritonavir + placebo b No treatment a No eRVR Week 4 EASL, Barcelona, Spain, 18–22 April 2012; Abstract 1412 eRVR a

30. INFORM-SVR: Mericitabine + danoprevir/ritonavir ± RBV in treatment-naïve GT-1 (Abstract 1412): Results Mericitabine + danoprevir/ritonavir + RBV Mericitabine + danoprevir/ritonavir + placebo HCV RNA ≤15 IU/mL at Week 4 (%) 9193 Mericitabine 1000 mg + danoprevir/ritonavir + RBV scheduled for 24 weeks (n=63) SVR8: Overall, % (n)41 (26/63) GT-1a26 (11/42) GT-1b71 (15/21) AEs, adverse events; SVR8: sustained virological response at Week 8 EASL, Barcelona, Spain, 18–22 April 2012; Abstract 1412 Four serious AEs and two discontinuations due to AEs in overall population

31. GS-7977 + RBV GS-7977 + PEG + RBV GS-7977 + RBV GS-7977 + PEG + RBV n= 9 n= 10 GS-7977 GT 2/3 Treatment-Naïve (GS-7977 + RBV +PEG) GS-7977 + RBV (GT 1 Null Responders) GS-7977 + RBV (GT 1 Treatment-Naive) GS-7977 + RBV (GT 2/3 Treatment-Experienced) n= 11 n= 10 n= 25 Wk 4Wk 8 Wk1 2 Wk 0 GT 2/3 Tx-naive Gane E, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1113. Electron Study: Treatment of GS-7977

32. Electron Study: Virologic Response GT 2/3 Treatment-naïve 8 wks (N=10) GT 1 Null Responders 12 wks (N=10) GT 1 Treatment-naïve 12 wks (N=25) GT 2/3 Treatment- experienced 12 wks (N=25) Week 16/10 (60)1/10 (10)7/25 (29)8/25 (32) Week 210/10 (100)7/10 (70)17/24 (71)21/25 (84) Week 410/10 (100) 25/25 (100) EOT10/10 (100)9/9 (100)25/25 (100)21/21 (100) SVR 410/10 (100)1/9 (11)22/25 (88)12/15 (80) SVR 810/10 (100)1/9 (11)- SVR 1210/10 (100)--- Patients with HCV RNA <LOD Over Time, n/N (%) Gane E, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1113.

33. Study AI444-040: Treatment with GS-7977 + BMS-790052 RBV: 1000-1200 mg daily according to body weight for GT1 patients ; 800 mg daily for GT2/3 patients N = 15 N = 16 N = 14 Chronic HCV GT1a/1b or GT2/3 infection, treatment-naive SVR 12 Week 24SVR 4 SVR 48 Week 1Week 4Week 12 Group C: (GT1a/1b) DCV 60 mg QD + GS-7977 400 mg QD Group D: (GT2/3) DCV 60 mg QD + GS-7977 400 mg QD Group D: (GT2/3) DCV 60 mg QD + GS-7977 400 mg QD Follow-up Group E: (GT1a/1b) DCV 60 mg QD + GS-7977 400 mg QD + RBV Group E: (GT1a/1b) DCV 60 mg QD + GS-7977 400 mg QD + RBV Follow-up N = 14 Group F: (GT2/3) DCV 60 mg QD + GS-7977 400 mg QD + RBV Group F: (GT2/3) DCV 60 mg QD + GS-7977 400 mg QD + RBV Follow-up N = 15 N = 14 Group A: (GT1a/1b) GS-7977 400 mg QD x 7d, then add DCV 60 mg QD Group A: (GT1a/1b) GS-7977 400 mg QD x 7d, then add DCV 60 mg QD Follow-up Group B: (GT2/3) GS-7977 400 mg QD x 7d, then add DCV 60 mg QD Group B: (GT2/3) GS-7977 400 mg QD x 7d, then add DCV 60 mg QD Follow-up Sulkowski M, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1422.

34. Study AI444-040: Key Results mITT analysis, bars not reaching 100% after Week 4 reflect missing values. PT, post treatment Sulkowski M, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1422. Week 2Week 4Week 12 Week 24 (EOT) PT Week 4 N= % < LOD % < LLOQ 677967100 93100878693100 SVR 4

35. Study AI444-040: SVR-4 according to genotype 1A/B and IL28B Overall SVR4 – 95.5% across GT 1,2 & 3 GT1: 100% of patients (44/44) achieved SVR4 No difference in SVR4 by HCV GT1 subtype or IL28B genotype Ribavirin did not increase the magnitude of HCV RNA decline or influence SVR Sulkowski M, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1422. IL28B Genotype (rs12979860)

36. Study AI444-040: GT2/3 Naïve Sulkowski M, et al. 47th EASL; Barcelona, Spain; April 18-22, 2012. Abst. 1422. N=44 GT2/3 SVR4=40/44 GT2/3 SVR4=40/44 GT2 Total n=26 SVR4=24/26 GT2 Total n=26 SVR4=24/26 GT3 Total n=18 SVR4=16/18 GT3 Total n=18 SVR4=16/18 GT2/3 – No RBV SVR4=28/30 2 viral failures GT2/3 – No RBV SVR4=28/30 2 viral failures GT2/3 + RBV SVR4=12/14 2 LTFU GT2/3 + RBV SVR4=12/14 2 LTFU 1 breakthrough (3a) 1 relapse (3a) 2 LTFU (2a, last RNA UND) 1 breakthrough (3a) 1 relapse (3a) 2 LTFU (2a, last RNA UND)

37. 2012 - 201X: Multiple DAA Combinations in Developmen Clinical trials to determine “best” combinations and minimum duration needed to achieve cure – Multiple regimens may lead to reduced cost per cure Role of Interferon alfa (lambda?) will evolve but not become extinct

38. TYPICAL DAY IN THE CLINIC, JUNE 201X

39. Patient 1 47 year old woman presents after being declined for life insurance – Infection likely due to blood shortly after birth – PMH: None – Social history: Married with 3 children; Recent change to new job with more responsibility – HCV genotype 1B; IL28B CC; Biopsy shows no fibrosis Treatment: – Oral therapy --- combination of 2 DAAs with no IFN and no RBV for 12 weeks ($$) – PegIFN/RBV ($)

40. Patient 2 66 year old man infected at age 20 via IDU – PMH: type 2 DM, hypertension, obesity, mild renal insufficiency; anemia; heroin use off/on (methadone); depression (incompletely controlled) – HCV genotype 1A; IL28B TT; Biopsy shows cirrhosis Treatment: – Multiple DAAs with nucleos(t)ide analogue ($$$) – No IFN due to contraindications

41. Patient 3 59 year old man otherwise healthy – HCV genotype 1A; IL28B TT; Biopsy shows Ishak 3/6 fibrosis Prior therapy – 1997: IFN alfa/RBV – stop at wk 24 with HCV RNA 5,500 copies/mL – 2011: PegIFN/RBV/Telaprevir – stop at wk 5 Week 0: 11,389,000 IU/mL (7.06 log10) Week 2: 17,710 IU/mL (4.25 log10) Week 4: 153, 060 IU/mL (5.18 log10) Treat: Multiple DAAs +/- IFN +/- RBV ($$$$)

42. Patient 4 59 year old man with decompensated liver disease – MELD = 25 – Ascites – HCC less than 2 CM on MRI Treatment: – :Multiple DAAs – pre or post-transplant ($$$$) – 5 year survival for HCV expected to be similar to similar to HBV

43. Patient 5 22 year old man tested positive for HCV EIA using finger stick test while attending needle exchange – Actively injecting heroin (~30 USD/day) uses new needles when he can – Staying with “friends” – HIV seronegative Lost to follow-up Treatment: – Contingent Incentive Care x oral DAAs for 12 weeks ($$) – Cost-effective with individual and public health benefit?

44. Future Treatment Paradigms Personalized medicine – Cost – Virus – 1A or 1B or other genotype; Resistance to DAAs – Patient – cirrhosis, ESLD, HCC, willing and able to take IFN alfa; substance abuse? Effectiveness may be limited by failure to translate to the infected populations