What s new in HCV/HIV coinfection therapy?

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1 What s new in HCV/HIV coinfection therapy? Mark Sulkowski, MD Professor of Medicine Johns Hopkins University School of Medicine Medical Director, Viral Hepatitis Center Divisions of Infectious Diseases and Gastroenterology/Hepatology Baltimore, Maryland

2 Disclosures PI for research grants related to HCV Funds paid to Johns Hopkins University AbbVie, BMS, Gilead, Janssen, Merck DSMB related to HBV Funds paid to Johns Hopkins University Gilead Scientific advisor/consultant related to HCV AbbVie, Achillion, BMS, Gilead, Janssen, Merck The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies

3 Typical comment from my colleagues in the era of highly effective DAAs Hey, great work on hepatitis C; simply amazing results..now, that hep C is done, what are you going to do with the rest of your career?

4 Hepatitis C: Challenges and Opportunity in the 21 st Century Challenge #1: High disease burden Challenge #2: Low rates of diagnosis and treatment despite available HCV cure Challenge #3: Development of and access to better HCV treatments Challenge #4: Prevention of new HCV infection and re-infection Challenge #5: HCV vaccine

Global prevalence: 130 150 million people have chronic HCV infection -- at least 5 million with HIV coinfection North America Europe, Western Europe, Central Europe, Eastern Asia,

3% 1.3%-2.9% Total Infected (Viremic) 0-200K 200K-650K 650K-1.9M 1.9M-3.5M Australasia 2.9%-7.8% 3.5M-9.

5 Global prevalence: million people have chronic HCV infection -- at least 5 million with HIV coinfection North America Europe, Western Europe, Central Europe, Eastern Asia, Central Asia Pacific, High Income Asia, South Caribbean Asia, Southeast Latin America, Central Asia, East Latin America, Tropical Prevalence (Viremic) 0.0%-0.6% 0.6%-0.8% 0.8%-1.3% 1.3%-2.9% Total Infected (Viremic) 0-200K 200K-650K 650K-1.9M 1.9M-3.5M Australasia 2.9%-7.8% 3.5M-9.2M Latin America, Southern Latin America, Andean North Africa/Middle East Sub-S Africa, Central Sub-S Africa, Southern Sub-Saharan Africa, West Razavi H, Gower E, Estes C, Hindman S. Global HCV Genotypes. AASLD 2013; 2013 Nov 1-5; Washington, DC, United States.

6 No. of deaths (millions) Global number of deaths in 2010 Hepatitis B and C HIV 1,6 1,4 1,2 1 0,8 0,6 0,4 0,2 0 HIV/AIDS Viral hepatitis Tuberculosis Malaria Global Burden of Disease Study 2010 Lozano et al, Lancet 2012

7 Hepatitis C: Challenges and Opportunity in the 21 st Century Challenge #1: High disease burden Challenge #2: Low rates of diagnosis and treatment despite available HCV cure Challenge #3: Development of and access to better HCV treatments Challenge #4: Prevention of new HCV infection and re-infection Challenge #5: HCV vaccine

8 Patients after 5 years (%) Patients after 5 years (%) HCV cure decreases the incidence of liver transplant, hepatocellular carcinoma, and death 5-year risk of death (all-cause) by SVR ,5 10,5 General: 18 studies n=29,269 Avg. FU=4.6 years SVR 3,6 No SVR 11,3 1,3 10 General Cirrhotic Co-infected Cirrhotic: 9 studies n=2,734 Avg. FU=6.6 years HIV/HCV: 5 studies n=2,560 Avg. FU=5.1 years 5-year risk of hepatocellular carcinoma by SVR ,9 9,3 General: 21 studies n=12,496 Avg. FU=6.1 years SVR 5,3 No SVR 13,9 0,9 10 General Cirrhotic Co-infected Cirrhotic: 18 studies n=4,987 Avg. FU=6.6 years HIV/HCV: 3 studies n=2,085 Avg. FU=4.7 years Meta-analysis of 129 studies of 34,563 patients Hill A. Clinical Infectious Disease 2015

9 Treatment Rate (%) Diagnosis and treatment rates are low 6% in most countries Bubble Area: Viremic HCV Prevalence France 5% Austria Germany 4% England Sweden 3% 2% Egypt Czech Republic Turkey Spain Switzerland Belgium Canada 1% Brazil Argentina Portugal Denmark Australia 0% 20% 40% 60% 80% 100% Diagnosis Rate (%)

10 Hepatitis C: Challenges and Opportunity in the 21 st Century Challenge #1: High disease burden Challenge #2: Low rates of diagnosis and treatment despite available HCV cure Challenge #3: Development of and access to better HCV treatments Challenge #4: Prevention of new HCV infection and re-infection Challenge #5: HCV vaccine

11 Interferon-based treatments have been a major barrier to effectiveness of treatment IL28B SNP and IFN response Side effects

12 HCV life cycle presents multiple antiviral targets 1. Entry 2. Endosomal release and IRES dependent translation 3. Protease cleavages 4. Membranous web formation 5. NS5B RNA dependent polymerase (RdRp) 6. Lipoprotein assembly linked to NS5A 7. Cellular targets Ray Fields Viology

13 HCV suppression by NS3 protease inhibitors Rapid and potent HCV suppression with BILN2061 (2003) Selection of telaprevir resistant variants with monotherapy x 14 days Lamarre Nature 2003 Kieffer Hepatology 2007 HCV Drug Development Advisory Group

14 HCV suppression by NS5A inhibitors Rapid and potent antiviral activity with a single dose of daclatasvir (2010) Selection of daclatasvir resistant variants with monotherapy x 14 days Gao Nature 2010 Nettles Hepatology 2011 HCV Drug Development Advisory Group;

15 HCV suppression by non-nucleoside NS5B polymerase inhibitors (non-nuc) Binding sites for non-nucleoside HCV NS5B polymerase inhibitors HCV RNA suppression over 3 days with dasabuvir (ABT-333) monotherapy (~ 1 log 10 ) Poordad EASL 2012

16 HCV cure with variable combinations of Paritaprevir/r + Ombitasvir + Dasabuvir + Ribavirin (NS3 ± NS5A ± non-nuc NS5B ± Ribavirin) N=41 83 N=79 N= N= No Ombitasvir (NS5A inhibitor) 12,2 10,1 7,6 No Dasabuvir (Non-nucleoside NS5B inhibitor) SVR (%) Viral Failure (%) 1,2 No Ribavirin Three DAAs + Ribavirin Kowdley NJEM 2014

Ribavirin prevents HCV virologic failure in patients with genotype 1a infection and is not required for 1b infection Ombitasvir/Paritaprevir + Dasabuvir with or with Ribavirin Genotype 1b 1 patient

17 Ribavirin prevents HCV virologic failure in patients with genotype 1a infection and is not required for 1b infection Ombitasvir/Paritaprevir + Dasabuvir with or with Ribavirin Genotype 1b 1 patient with breakthrough* Genotype 1a - No Ribavirin 16 patients with virologic failure (6 breakthrough and 10 relapse)* Genotype 1a plus Ribavirin 2 patients with virologic failure (1 breakthrough and 1 relapse)* *Variants in patients with virologic failure: NS3, D168V NS5A, M28T and Q30R NS5B,S556G Ferenci NEJM 2014

18 Patients, % SVR C-EDGE treatment-naive study: 12-week regimen of grazoprevir/elbasvir (GZR/EBR) in G1/4/6 patients / / /131 18/18 8/10 All pts Non-cirrhotics Cirrhotics G1a G1b G4 G6 4 Non-VF Good safety and tolerability profile: No drug-related SAE; 2 deaths unrelated to drugs 1 Breakthrough Relapse Lab: No concurrent ALT/Bili increase, no anemia 231/246 68/70 VF = virologic failure Zeuzem S, et al. EASL 2015, Vienna. #G07

19 C-EDGE treatment-naive study: 12-week regimen of grazoprevir/elbasvir (GZR/EBR) in G1/4/6 patients NS5A RAVs RAV status in pts with BL sequence % (n/m) SVR12 All pts % (N/n) SVR12 NS5A RAVs 5-fold potency loss SVR12 NS5A RAVs >5-fold potency loss G1a RAVs BL NS5A RAVs 12 (19/154) 58 (11/19) 90 (9/10) 22 (2/9) No BL NS5A RAVs 88 (135/154) 99 (133/135) G1b RAVs BL NS5A RAVs 14 (18/130) 94 (17/18) 100 (1/1) 94 (16/17) No BL NS5A RAVs 86 (112/130) 100 (112/112) m: pts with evaluable BL sequence; n: number of pts with/without BL RAVS; N: pts who achieved SVR All pts with virologic failure had BL HCV RNA of >800,000 IU/mL SVR was achieved by 95% of pts Lower SVR in G1a accounted for by high-level (>5x fold) NS5A RAVs in G1a Although such RAVs uncommon (6% of G1a), BL NS5A testing with high BL VL might be needed to identify need for RBV, longer duration, or selection of a different regimen Well tolerated, with similar safety profile and similar efficacy in cirrhotic and noncirrhotic patients Zeuzem S, et al. EASL 2015, Vienna. #G07

20 SVR12 (%) GZR/EBR ± RBV for 12 weeks in G1/4 patients who previously failed PegIFN/RBV: C-EDGE treatment-experienced trial SVR according to baseline factors Overall G1a Non-cirrhotic Cirrhotic Partial or null reponse SVR according to BL NS3 and NS5 RAVs Total NS3 variants not detectable SVR12 n/n (%) NS3 RAVs 5-fold shift NS3 RAVs >5-fold shift G1a 95% 107/112 (96%) 104/111 (94%) 0 G1b 99% 133/135 (99%) 9/9 (100%) 1/1 (100%) NS5A variants not detectable NS5A RAVs 5-fold shift NS5A RAVs >5-fold shift G1a 95% 190/192 (99%) 10/10 (100%) 11/21 (52%) G1b 99% 127/127 (100%) 0 16/18 (89%) Kwo P, et al. EASL 2015, Vienna. #P wk no RBV 12-wk + RBV 16-wk no RBV 16-wk + RBV GZR/EBR FDC ± RBV was safe and effective in PR non-responders 16 weeks + RBV achieved 100% SVR in cirrhotic null responders 12/14 G1 failures had high-level NS5A RAVS at baseline An intensified regimen is needed to overcome impact of baseline NS5A RAVs, especially in G1 pts Baseline NS5A testing advisable with this regimen now that commercially available

21 Patients (HCV RNA <LLQ, %) C-SURFER: GZR + EBR in treatment-naive and treatmentexperienced patients with HCV G1 infection and CKD 66 81/ 122 Virologic response (ITG) / 121 TWk2 TWk4 TWk12 (EOT) 1 G1b, non-cirrhotic, patient relapsed at FWk12 ITG: Immediate treatment group Roth D, et al. EASL 2015, Vienna. #LP / / 118 FWk4 115/ 116 FWk12 (SVR12) All patients 115/116 Cirrhosis Yes 6/6 No 109/110 HCV genotype G1a G1b Race White African-American Previous tx Naive Experienced CKD stage 4 5 Diabetes Yes No Hemodialysis Yes No SVR12 subgroup analyses (ITG) 61/61 54/55 58/59 51/51 96/96 19/20 22/22 93/94 40/41 75/75 86/87 29/29 SVR12 (95% CI)

22 HCV suppression by nucleos(t)ide analogue NS5B polymerase inhibitors Sofosbuvir, β-d-2'-deoxy-2'-α-fluoro-2'-β-cmethyluridine nucleotide prodrug (2010) Potent HCV suppression with sofosbuvir alone, with ribavirin or with both interferon/ribavirin (2010) Sofia J Med Chem 2010 Gane NEJM 2013 HCV Drug Development Advisory Group

23 Patients (%) OPTIMIST-1: 8- or 12-week regimen of simeprevir (SIM) + sofosbuvir (SOF) in G1 patients without cirrhosis SVR12 rates 12 wks 8 wks / / / 40 40/ 52 54/ 56 46/ 48 96/ 99 82/ / / / 46 36/ 49 68/ 70 56/ 67 38/ 39 36/ 39 43/ 43 38/ 41 83/ 86 72/ 86 24/ 26 18/ 28 IL28B genotype Kwo P, et al. EASL 2015, Vienna. #LP14 High overall SVR12 rate (97%) for 12-week treatment duration Q80K was not impactful in this non-cirrhotic population Lower overall SVR12 rate (83%) for 8-week duration not a viable option, unlike LDV/SOF, for treatment naive G1 non-cirrhotics Reason for lower efficacy of SMV than LDV with SOF for 8 weeks unclear do NS5A inhibitors degrade the replicase complex faster?

24 Proportion of patients (%) OPTIMIST-2: A Phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of SMV + SOF in treatment-naive or -experienced G1 cirrhotic patients /50 42/53 68 Treatmentnaive Treatmentexperienced SVR12 did not differ between IL28B genotypes Lawitz E, et al. EASL 2015, Vienna. #LP04 87 SVR12: SMV + SOF 12 weeks Expands COSMOS + TRIO/TARGET data in clinical trials No RBV; Q80K adversely influenced response; would need BL testing before using regimen in cirrhotics 18% increase in bilirubin Lost opportunity to explore (approved) 24-week regimen 92 G1a G1a with Q80K G1a without Q80K 84 60/72 25/34 35/38 26/31 13/19 73/84 39/53 47/50 12/15 11/11 Platelets <90,000/mm Platelets 90,000/mm 3 3 Albumin <4 g/dl 94 Albumin 4 g/dl 80 FibroScan score >20 kpa G1b 100 FibroScan score > kpa

25 HCV eradication with the fixed-dose combination of Ledipasvir/Sofosbuvir (NS5A/nuc NS5B) Persons with no prior HCV treatment weeks 20 patients with relapse, 4.6% HCV RNA < 6 million IU/mL, 2% weeks 4 patients with relapse, 0.6% 24 weeks 1 patient with relapse, 0.2% weeks 12 weeks 24 weeks Ribavirin No Ribavirin *Variants in patients with virologic failure: NS5A, L31V/M/I, Y93H, Q30R NS5B, None Kowdley KV et al. N Engl J Med May 15;370(20): Afdhal N et al. N Engl J Med May 15;370(20):

genotype 1 6 GS5816 - potent antiviral activity HCV genotype 1 6 Phase 3

26 HCV cure genotypes 1, 2, 3, 4, 5 and 6 with the combination of sofosbuvir/gs5816 (nucns5b/ns5a) Sofosbuvir - potent antiviral activity HCV genotype 1 6 GS potent antiviral activity HCV genotype 1 6 Phase 3 clinical trials are underway for the fixed dose combination of Sofosbuvir/GS5816 Everson EASL 2014

SVR Rate (%) 100 80 There has been great progress toward more efficacious HCV treatments but Years are not to scale 1986 1998 2001 2002 2011 2013 *Year of data presentation at EASL 2014 and

27 SVR Rate (%) There has been great progress toward more efficacious HCV treatments but Years are not to scale *Year of data presentation at EASL 2014 and publication in N Engl J Med * IFN 6 mo IFN 12 mo IFN+RBV 6 mo IFN+RBV 12 mo PEG 12 mo PEG+RBV 12 mo PI+PEG +RBV 6-12 mo SMV+PEG +RBV 6-12 mo SOF+PEG +RBV 3 mo LDV/SOF or 3D 2-3 mo Adapted from Strader DB, et al. Hepatology. 2004;39: Incivek (telaprevir) [package insert]. Cambridge, MA: Vertex Pharmaceuticals; May, VICTRELIS (boceprevir) [package insert]. Whitehouse Station, NJ: Merck & Co; Jacobson I, et al. EASL 2013; Amsterdam, The Netherlands. Poster #1425. Manns M, et al. EASL Amsterdam, The Netherlands. Oral #1413. Lawitz E, et al. APASL Singapore. Oral #LB-02; Afdhal N, et al. N Engl J Med. 2014;370: ; Kowdley K, et al. N Engl J Med. 2014;370:

28 56-year-old man with HIV/HCV genotype 1/subtype A Cirrhosis: MELD 15 with Cr 1.6, INR 1.3, bili 1.3; IL28B TT HIV: Atazanavir/r + raltegravir + TDF/FTC with CD4 249 and HIV RNA < 20 c/ml HCV treatment 2011: PegIFN/RBV + telaprevir breakthrough At treatment week 4, HCV RNA = 46 IU/mL; week 12, HCV RNA = 1,299 IU/mL 2014: Sofosbuvir + ribavirin breakthrough Baseline HCV RNA = 2,506,896 IU/mL Week 4 = 36 IU/mL Week 12 = not detected Week 16 = Detected < 43 IU/mL Week 24 = 2,119 IU/mL (on-treatment) despite 100% adherence

29 Courtesy of Dr. Stuart Ray

30 SVR12 (%) Retreatment of patients who failed 8 or 12 weeks of LDV/SOFbased regimens with LDV/SOF for 24 weeks / 14/ 24/ 5/ 11/ 18/ No Yes 8-wk 12-wk No Yes Cirrhosis Prior treatment duration Baseline NS5A RAVs / 11 11/ 16 7/ 14 None 1 2 Number of NS5A RAV(s) / 5 Q30R or M28T 4/ 5 L31M 2/ 6 Y93H/N Type of single NS5A RAV Shorter therapies produce less-frequent treatment-emergent RAVs More complex RAV pattern = less likely to achieve response Retreatment with longer duration more likely to be successful with fewer NS5A RAVs or RAVS with smaller shifts in EC 50 Lawitz E, et al. EASL 2015, Vienna. #O005

31 SVR12 (%) The prevalence and effect of HCV NS5A resistance-associated variants in subjects with compensated cirrhosis treated with LDV/SOF ± RBV 513 patients with G1 and compensated cirrhosis were pooled from Phase 2 and 3 LDV/SOF ± RBV studies 20/513 failed to achieve SVR12 18 patients relapsed 2 patients excluded from resistance analysis (1 lost to FU, 1 death) Overall SVR12 rates in patients with and without NS5A RAVs* With RAVs No RAVs / 26 86/ 91 LDV/SOF 12 weeks Sarrazin C, et al. EASL 2015, Vienna. #P / / 169 LDV/SOF + RBV 12 weeks 17/ / 113 LDV/SOF 24 weeks 14/ 14 44/ 44 LDV/SOF + RBV 24 weeks *Presence of RAVs was evaluated by deep sequencing with assay cutoffs of 1%; error bars represent 95% CIs

32 Ribavirin prevents the emergence of resistance associated variants during antiviral therapy HCV breakthrough with or without ribavirin during telaprevir/peginterferon NS3 protease + non-nuc NS5B polymerase inhibitor + No Ribavirin Telaprevir + Peginterferon Telaprevir + Peginterferon/Ribavirin Zeuzem Hepatology 2012 Hezode NEJM 2009 NS3 protease + non-nuc NS5B polymerase inhibitor + Ribavirin

33 Treatment with GS SOF/GS-5816 in treatment-naive and DAA-experienced G1 patients with and without cirrhosis Aim: Triple therapy with SOF plus 2nd-gen NS5A inhibitor (GS-5816) and NS3/4A (GS-9857) could reduce treatment duration across patient populations Study design Week G1 TN no cirrhosis n=30 TN cirrhosis n=15 SOF/GS GS-9857 SOF/GS GS-9857 SOF/GS GS-9857 SVR12 SVR12 SVR12 DAA failure n=30 SOF/GS GS-9857 SVR12 Baseline Characteristics 4 weeks n=15 6 weeks n=15 6 weeks n=15 6 weeks n=30 Mean age, y (range) 54 (40 64) 50 (24 65) 59 (51 66) 55 (35 73) Male, n (%) 9 (60) 7 (47) 11 (73) 24 (80) White, n (%) 12 (80) 14 (93) 14 (93) 27 (90) Mean BMI, kg/m 2 (range) 27 (20 33) 25 (21 32) 27 (20 39) 27 (20 40) IL28B CC, n (%) 5 (33) 5 (33) 8 (53) 6 (20) Cirrhosis, n (%) (100) 5 (17) Mean HCV RNA, log 10 IU/mL (range) 6.3 ( ) 6.0 ( ) 6.0 ( ) 6.3 ( ) HCV G1a, n (%) 11 (73) 11 (73) 14 (93) 23 (77) Gane E, et al. EASL 2015, Vienna. #LP03 DAA failures Delobuvir + faldaprevir + RBV (n=4) LDV/SOF + RBV (n=1) DCV + VX135 (n=3) Telaprevir + VX222 ± RBV (n=2) 3% 10% 13% 20% 7% Danoprevir + mericitabine + ritonavir ± RBV (n=6) 47% Danoprevir + mericitabine (n=14)

34 Patients (%) Short-duration treatment with GS SOF/GS-5816 in treatment-naive and DAA-experienced G1 patients with and without cirrhosis Results: SVR /15 14/15 13/15 20/30 TN NC G1 TN NC G1 TN cirrhotic DAA failures 4 weeks 6 weeks 6 weeks 6 weeks RAVs at virologic failure (relapse) NS NS5A NS5B Only 3/10 subjects have been sequenced Predictors of SVR (univariate) Younger age, lower BL HCV RNA Not IL28B C, AUC, or BL RAVs Safety AEs mild, non-specific Any AE in 58/75 (77%) No Grade 3/4 AE, SAE or d/c Lab abnormality in 7 pts (4 transient lipase) Gane E, et al. EASL 2015, Vienna. #LP03 67 Impact of BL RAVs (deep sequencing) Treatment naive ± cirrhosis, n=43* 62% SVR12 16/26 60% without n=26/43 *2 pts without BL sequence data Prior DAA failure ± cirrhosis, n=30 65% SVR12 11/17 57% without n=17/30 40% with n=17/43 43% with n=13/30 82% SVR12 14/17 69% SVR12 9/13 SOF/GS GS-9857 is safe and well tolerated In G1 TN without cirrhosis, 6 weeks triple DAA was effective, but shortening to 4 weeks was associated with >70% relapse without RAVs In G1 cirrhotics and DAA failures, duration longer than 6 weeks should be considered Threshold for duration regardless of DAA number?

35 Hepatitis C: Challenges and Opportunity in the 21 st Century Challenge #1: High disease burden Challenge #2: Low rates of diagnosis and treatment despite available HCV cure Challenge #3: Development of and access to better HCV treatments Challenge #4: Prevention of new HCV infection and re-infection Challenge #5: HCV vaccine

36 HCV is a sexually transmitted disease among HIV-infected MSMs Incidence of HCV in HIV-infected MSM from 12 cohorts within CASCADE Fierer DS et al. MMWR July 22, 2011; van der Helm JJ et al. AIDS 2011, 25:

37 Incidence /100 PY Incidence of hepatitis C reinfection following SVR: 7-year followup of Scandinavian patients infected through injecting drug use Patients : Multicentre study comprising 428 Scandinavian G2 or G3 patients Incidence of reinfection SVR 76%; 68% PWID, abstinent from drug use 6 months prior to treatment : 94 PWID and 44 non-pwid with SVR Median f/u of years Results 37 of 94 (39%) PWID relapsed to active injection after SVR HCV reinfection in 12 patients; of whom 11 were active PWID ,8 Pts with injecting drug use prior to treatment 4,7 Relapsed to injecting during f/u 0,32 No history of injecting drug use Midgard H, et al. EASL 2015, Vienna. #O061

38 Incidence of HCV infections in young adults in the US

39 Hepatitis C: Challenges and Opportunity in the 21 st Century Challenge #1: High disease burden Challenge #2: Low rates of diagnosis and treatment despite available HCV cure Challenge #3: Development of and access to better HCV treatments Challenge #4: Prevention of new HCV infection and re-infection Challenge #5: HCV vaccine

rs12979860 C IL-28B allele associated with higher probability of natural clearance of HCV Thomas DL, et

40 rs C IL-28B allele associated with higher probability of natural clearance of HCV Thomas DL, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009; 461(7265):798

41 Shorter duration of viremia during reinfection among PWID with prior infection/spontaneous clearance Osburn et. al. Gastroenterolgy 2010;138:

42 HCV Prophylactic Vaccine Based on Sequential Use of Chimpanzee Adenovirus AdCh3and MVA with NS Cross reactivity of AdCh3 with human antiadenovirus Abs is 12% MVA boosts well in Phase I trials Double-blinded, randomized, placebo-controlled two stage study. Subjects: HCV Ab and RNA negative, active IDU s at high risk for HCV, y.o. Two Sites (UCSF, JH) W0 W8 W50 AdCh3 2.5 x10 10 vp MVA 1.8x10 8 pfu W = week = test immune response

43 Hepatitis C: Challenges and Opportunity in the 21 st Century Globally, chronic infection with HCV is a major cause of death HCV cure is associated with improved survival Oral, interferon-free HCV treatment regimens involving two or more directing acting antivirals which target unique viral mechanism have been developed Rapid, remarkable translation of laboratory discoveries into approved drugs If treated, most individuals can be cured Unanswered questions about drug resistance in persons who are not cured Current challenge: Translation of clinical trial findings into global community effectiveness HCV vaccine is needed

Antivirals for the treatment of chronic HCV infection: Bench to Bedside and beyond

Antivirals for the treatment of chronic HCV infection: Bench to Bedside and beyond Mark Sulkowski, MD Professor of Medicine Johns Hopkins University School of Medicine Baltimore, Maryland Disclosures for