Current State of Treatment for HCV. Nancy Reau, MD Associate Professor of Medicine University of Chicago

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1 Activity Code FA376

2 Current State of Treatment for HCV Nancy Reau, MD Associate Professor of Medicine University of Chicago

3 Learning Objectives Upon completion of this presentation, learners should be better able to: 1. Discuss the safety and efficacy of current treatment options for HIV and HCV 2. Discuss the safety and efficacy of near term agents for those co-infected 3. Review the pipeline of HCV agents in phase 2/3 trials for HCV mono-infection

4 Disclosures Grant Support: Vertex, Genentech, Janssen, Gilead, AbbVie, BMS, Boehringer- Ingelheim Medical Advisory: AbbVie, Gilead, Janssen, Idenix, Salix

5 Cumulative mortality (%) HCV Viral Replication Increases All Cause Mortality All Causes Anti-HCV seropositives, HCV RNA detectable Anti-HCV seropositives, HCV RNA undetectable Anti-HCV seronegatives 30.1% 25 P<0.001 for comparison among three groups P<0.001 for HCV RNA detectable vs. undetectable % 12.4% Follow-up years Lee MH, et al. J Infect Dis. 2012;206(4):

6 All-cause mortality, % Liver-related mortality or liver transplantation, % Viral Eradication is Associated with Reduced Mortality SVR=CURE HCV PCR negative weeks after stopping therapy 530 Europeans followed median 8.4 years after HCV treatment 192 (36%) achieved SVR P<0.001 All-cause mortality Liver-related mortality or liver transplantation P< Without SVR Time, y With SVR No. at risk Without SVR With SVR Without SVR Time, y With SVR No. at risk Without SVR With SVR Van der Meer, et al. JAMA 2012:308:

7 Which of the following does not improve with SVR? A. Lower rate of liver cancer B. Lower rate of liver transplant C. Lower rate of overall death D. Lower rate of AIDS death E. All of these are true 20% 20% 20% 20% 20% A. B. C. D. E. 8

8 SVR Improves Outcomes 711 HIV-HCV; 31% with SVR Berenguer et al. Hepatology 2009;50:

9 Antiretroviral-treated co-infected patients have WHAT rate of hepatic decompensation compared to those mono-infected with HCV? A. The same B. Lower C. Higher D. We don t know 25% 25% 25% 25% A. B. C. D. 8

10 Co-infected Patients have Higher Rates of Hepatic Decompensation Despite ART Lo Re et al. Ann Intern Med. 2014:160:

11 Co-infected Patients have Higher Rates of Hepatic Decompensation Despite ART Lo Re et al. Ann Intern Med. 2014:160:

12 Meet Maya Maya is HIV-HCV infected and very interested in treatment. She has never received HCV therapy HCV G1A, Excellent hepatic function, Plts 220K

13 What therapy would you suggest? A. Begin PEG- IFN/RBV/telaprevir (TVR) B. Begin PEG- IFN/RBV/boceprevir (BOC) C. Begin therapy for PEG- IFN/RBV/ simeprevir (SMV) D. Begin therapy for PEG- IFN/RBV/sofosbuvir (SOF) E. Defer therapy for all-oral option 0% 0% 0% 0% 0% A. B. C. D. E.

14 Treat Now or Wait? Three Major Issues Urgency of Treatment Degree of injury Risk of progression Extrahepatic manifestations Toxicity of therapy Probability of Cure

15 The historical perspective: Treatment of Coinfection vs. Monoinfection 48 weeks PEG+RBV Hadziyannis et al. Ann Int Med 2004; Fried et al. NEJM 2002; Torriani et al NEJM 2004; Nunez et al (PRESCO) AIDS Res Human Retro 2007

16 Milestones in Therapy of HCV: Overall SVR Rates (Mono-infection) Average SVR Rates from Clinical Trials %* 68%* % 54-56% 34% 42% 39% 42-46% 6% 16% Peg-IFN/ RBV 12m DAA+DAA DAA+PR Adapted from Strader DB, et al. Hepatology. 2004;39(4): Hezode C, et al. N Engl J Med. 2009; 360(18): Kwo P, et al. Presented at: EASL; April 23, 2009; Copenhagen, Denmark. Abstract 4. Kwo PY, et al. Lancet. 2010;376(9742): Jacobson IM, et al. N Engl J Med. 2011;364: ; Poordad F, et al. N Engl J Med. 2011;364(13): Telaprevir prescribing information at Accessed September 12, 2012.

17 Currently Available Agents Protease Inhibitor (PI) Boceprevir (TID) Telaprevir (TID) Simeprevir (QD) Additional Regimen Components PEGIFN alfa + weight-based RBV Considerations Genotype Naïve Previous treatment failure Compensated cirrhosis Response guided therapy Polymerase Inhibitor Additional Regimen Components Sofosbuvir (QD) PEGIFN alfa + weight-based RBV Considerations SOF+RBV for genotype 2/3 SOF+PEG/RBV G1 PEGIFN alfa = peginterferon alfa RBV = ribavirin

18 Simeprevir (SMV) + PEG-RBV SMV 150mg QD + PEG-IFN + RBV PEG-IFN + RBV f/u 24 wk Continue therapy only if HCV RNA <25 IU/mL at Week Weeks 48 Fried MW, et al. Hepatology Aug 2:0. doi: /hep

19 Proportion of patients (%) Proportion of patients achieving SVR12 (%) SVR Rates High in Mono-infected Treatment-naïve Sustained Virological Response (SVR12) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% P<0.001* 210/264 65/130 SMV 150 mg QD + PR 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% SVR12 85% met criteria to continue treatment 91% SMV + PR *Controlling for stratification factors PR, peginterferon + ribivarin; SVR12, sustained virological response (HCV RNA undetectable) 12 weeks after planned treatment Adapted from Jacobson IM, et al. Presented at Digestive Disease Week 2013; May 18-21; Orlando, FL. Sa2072.

20 Overview of PI Adverse Events Telaprevir: Adverse Event, % Telaprevir Containing Arms (n = 1797) PEG-IFN/RBV Arm (n = 493) Rash Pruritus Anemia* Anorectal AEs** 29 7 **Hemorrhoids, anorectal discomfort, anal pruritus, and rectal burning Boceprevir: Adverse Event, % Boceprevir Containing Arms (n = 734) PEG-IFN/RBV Arm (n = 363) Anemia* Dysgeusia Simeprevir: Adverse Event, % Simeprevir Containing Arms (n = 781) PEG-IFN/RBV Arm (n = 397) Rash (+photosensitivity) Pruritus Nausea Myalgia

21 Sofosbuvir G1 PATIENTS SOF 400 mg QD + PEG-IFN + RBV f/u 24 wk Weeks 48 G2/3: ALL ORAL THERAPY SOF 400 mg QD + RBV G3 G2 NR Weeks 48 Lawitz EM, et al. N Engl J Med. 2013;368:

22 SVR Rates in Treatment-Naive Patients Treated with Sofosbuvir+PEG/RBV / / / /327 On treatment Post-treatment Relapse accounted for all virologic failures Lawitz EM, et al. Presented at EASL: The International Liver Congress 2013; April 24-28, 2013; Amsterdam, The Netherlands. Abstract 1411.

23 SVR 12 (%) Sofosbuvir + RBV is an All Oral Therapy in Genotype 2 and P <0.001* Total G2 G3 Cirrhosis *Study met primary endpoint of noninferiority of SOF + RBV to PEG-IFN + RBV. FISSION: SOF + RBV in Treatment-naïve, Genotype 2 or 3 Patients Adapted from Lawitz EM, et al. N Engl J Med. 2013;368(20): PEG- IFN/RBV SOF/RBV

24 Effect of Treatment Duration with Sofosbuvir Plus RBV in HCV Genotype 3 Infected Patients FDA Analysis of FISSION, POSITRON, FUSION, VALENCE wks 24 wks 12 wks 16 wk 24 wk Treatment naïve SVR Relapse Treatment Experienced Mishra P. on behalf of the FDA Sofosbuvir Review Team. October 25, 2013

25 Off-label Treatment Options: COSMOS Study: Simeprevir + Sofosbuvir + RBV in HCV Monoinfection Phase 2a HCV genotype 1 Prior null response HCV RNA >10,000 IU/mL F0-F2 fibrosis Simeprevir + Sofosbuvir + RBV Simeprevir + Sofosbuvir Follow-Up Follow-Up Advanced fibrosis, experienced and Naïve to direct acting antivirals Excluded: HBV or HIV infection Simeprevir + Sofosbuvir + RBV Simeprevir + Sofosbuvir Follow-Up Follow-Up Simeprevir 150 mg qd, sofosbuvir 400 mg qd. Weight-based ribavirin dosing (1000 or 1200 mg bid). Week SVR4 Interim Analysis Lawitz E, et al. 20 th CROI. Atlanta, Abstract 155LB.

26 What Off-label Treatment Options may Exist? COSMOS: Sofosbuvir + Simeprevir ± RBV in GT1 Week 12 Treatment Duration Phase 2a Study: SOF 400 mg QD + SMV 150 mg QD ± RBV x 12 wks Prior null responder patients (F0-F2)* Prior null responder and treatment-naïve patients (F3 or F4) % 26/27 13/14 26/27 14/14 *Similar rates in G1a and 1b SVR 8wks (%) SVR 4wks (%) Lawitz et al. Presented at CROI 2013, Abstract 155LB. Medivir announces interim results from Cohort 2 of the COSMOS study evaluating Simeprevir and Sofosbuvir in HCV patients with METAVIR scores F3-F4. Accessed September 3, 2013.

27 The efficacy of HCV therapy is the same in HIV/HCV as in HCV mono-infection. A. True B. False 0% 0% A. B.

28 TVR+PEG+RBV Naïve HCV G1 with HIV

29 TVR+PEG+RBV SVR 12

30 BOC+PEG+RBV Naïve HCV G1 with HIV Sulkowski M et al. Abstract #47 CROI 2012

31 BOC+PEG+RBV Naïve G1 with HIV Virologic Response Over Time Sulkowski M et al. Abstract #47 CROI 2012

32 ANRS HC26 TelapreVIH Study: Telaprevir- Based HCV Therapy in HCV/HIV Coinfection Phase 2 (n=69) HIV positive HCV genotype 1 Previously failed PR On stable ART CD4 >200 cells/mm 3 HIV RNA <50 copies/ml EPO, G-CSF, TPO-R agonists allowed Excluded: Decompensated cirrhosis HBV or HIV-2 infection Previous null response with cirrhosis PR Lead In Telaprevir + PR Follow-Up Week RVR 8 EVR 16 (HCV RNA <15 IU/mL) Complete RVR 8 Telaprevir + PR Partial RVR 8 Telaprevir + PR SVR 24 Follow-Up SVR 24 PR: peginterferon + ribavirin. Telaprevir 750 mg q8h (1125 mg q8h with efavirenz). Weight-based ribavirin dosing ( mg bid). Telaprevir stopping rules: HCV RNA >1000 IU/mL at week 8 or 12; virologic breakthrough at anytime. ART: ATV/r + FTC/TDF (49%); EFV/FTC/TDF (19%); RAL + FTC/TDF (17%). Baseline characteristics: mean age (50 years); male gender (80%); former IDU (55%); CDC stage C (19%); mean CD4 (630 cells/ml); HIV RNA <50 copies/ml (99%); HCV genotype 1a (70%). Cotte L, et al. 20 th CROI. Atlanta, Abstract 36.

33 Patients (%) ANRS HC26 TelapreVIH Study SVR24 by Baseline Characteristics % 81% 75% 71% 75% 90% 85% 81% 78% 74% 83% 100% 71% Overall (n=69) ATV/r EFV RAL 1A 1B TT F1/2 F3/4 Relapse Break through ART (n=34/13/12/10) HCV Subtype IL28B Genotype Fibrosis Stage Partial Null Previous Response (n=27/6/15/21) Cotte L, et al. 21 th CROI Abstract 668.

34 ANRS HC27 BocepreVIH Study: Boceprevir- Based HCV Therapy in HCV/HIV Coinfection Phase 2 (n=64) HIV positive HCV genotype 1 Previously failed PR On stable ART CD4 >200 cells/mm 3 HIV RNA <50 copies/ml EPO, G-CSF, TPO-R agonists allowed Excluded: Decompensated cirrhosis Child B-C cirrhosis HBV or HIV-2 infection Previous null response with cirrhosis PR Lead In Boceprevir + PR Complete RVR 8 Follow-Up Week RVR 8 EVR 16 (HCV RNA <15 IU/mL) PR Partial RVR 8 SVR 24 Follow-Up SVR 24 PR: peginterferon + ribavirin. Boceprevir 800 mg tid. Weight-based ribavirin dosing ( mg bid). Boceprevir stopping rules: HCV RNA >1000 IU/mL at week 8 or 12; virologic breakthrough at anytime. ART: ATV/r + 2 NRTIs (50%); RAL + 2 NRTIs (42%). Baseline characteristics: mean age (52 years); male gender (75%); former IDU (73%); CDC stage C (22%); mean CD4 (728 cells/ml); HIV RNA <50 copies/ml (95%); HCV genotype 1a (78%). Poizot-Martin I, et al. 20 th CROI. Atlanta, Abstract 37.

35 Patients (%) ANRS HC27 BocepreVIH Study: SVR 12 Results % % 70% 56% 54% 60% 54% 61% 40 41% 40% 43% 24% 20 0 Overall (n=64) ATV/r RAL Others F0/1 F2 F3 TT CC Relapse Partial Null ART (n=32/27/5) Fibrosis Stage (n=21/18/14/11) IL28B Genotype Previous Response (n=20/5/18/21) Poizot-Martin I, et al. 21 th CROI, 2014 Abstract 659LB.

36 Telaprevir and Boceprevir Safety Few discontinuations due to toxicity Proactive anemia management decreased impact of anemia No unexpected adverse events No HIV breakthrough TVR/BOC strong inhibitor of CYP3A4 ART limited Poizot-Martin I, et al. 20 th CROI. Atlanta, Abstract 37. Sulkowski et al. Ann Intern Med 2013;159:86-96

37 Second Wave HCV Therapy Telaprevir and Boceprevir are no longer 1 st line therapy 1. Simple rules 2. Shorter duration of therapy 3. More effective 4. Less drug interactions 5. Less side effects

38 Therapeutic Targets for Direct Acting Antiviral Drug Development Poordad, J Viral Hep, 2012;19: Structural Proteins Hepatitis C Virus Polyprotein Core E1 E2 P7 NS2 NS3 4A NS4B NS5A NS5B Non-Structural Proteins Protease Inhibitors NS5A Inhibitors NS5B Nucleoside Inhibitors NS5B Non-Nucleoside Inhibitors High Potency Multi-genotypic coverage Intermediate to high barrier to resistance High Potency Multi-genotypic coverage Low to intermediate barrier to resistance Intermediate Potency Pan-genotypic coverage High barrier to resistance Intermediate Potency Limited genotypic coverage Low barrier to resistance

39 Second-wave protease inhibitors in HIV/HCV Coinfection

40 Phase III Faldaprevir + PEG/RBV treatment-naïve and relapser patients HCV GT- 1 and HIV infection Dieterich D et al.. STARTVerso 4. 21st Conference on Retroviruses and Opportunistic Infections, 2014; abstract 23

41 SVR in HIV/HCV co-infected patients: Phase III Faldaprevir + PEG/RBV treatment-naïve and relapsers Dieterich D et al.. STARTVerso 4. 21st Conference on Retroviruses and Opportunistic Infections, 2014; abstract 23

42 Study C212: Simeprevir + PR HIV/HCV Coinfection Phase 3 (n=106) On ART (88%) Primary endpoint: SVR12 HCV Treatment-Naïve Relapse Response Guided Therapy Simeprevir + PR Simeprevir + PR PR PR Follow-Up Follow-Up HCV Partial Response HCV Null Response Cirrhotic (F4) Simeprevir + PR Follow-Up Week PR PR: peginterferon + ribavirin. Simeprevir 150 mg qd. ART: NRTI (3TC, ABC, FTC, TDF): 99%. Raltegravir: 87%. Rilpivirine: 15%. Maraviroc: 3%. Enfuvirtide: 3%. Dieterich D, et al. 21 st CROI Abstract 24.

43 Patients (%) Study C212: SVR12 Simeprevir + PR in HIV/HCV Coinfection SVR12 74% 79% 87% 70% 89% 60 57% Overall Naïve Relapse Partial Null RGT-Eligible (n=54/61) PR: peginterferon + ribavirin. Dieterich D, et al. 21 st CROI Abstract 24.

44 Study C212: HCV Relapse and Safety HCV relapse Treatment-naïve and prior relapse: 16% All genotype 1a Prior null responders: 64% No HIV virologic failures Average CD4 cell decline: 670 to >380 cells/mm 3 Simeprevir + PR was well tolerated, with similar safety profile in HCV-monoinfected patients Fatigue (41%), nausea (26%), headache (27%) Neutropenia (27%), anemia (21%), pruritus (20%), rash (17%), photosensitivity (2%) Increased bilirubin (5%) Dieterich D, et al. 20 th CROI. Atlanta, Abstract 154LB.

45 Interferon-Free Treatment HCV Monoinfection Several 8-24 week Interferon Free regimens have demonstrated high efficacy in HCV mono-infected patients

46 SAPPHIRE-I: INF-FREE, 12-WEEK ABT-450/r/ABT-267, ABT-333, + RIBAVIRIN TREATMENT-NAÏVE G1 (N=631) Double-Blind Treatment Period 3D + RBV (n=473) Open-Label Treatment Period 48-Week Follow-Up Placebo (n=158) 3D + RBV 48-Week Follow-Up Week 0 Week 12 Week 24 Week 60 Week 72 Primary Analysis: SVR 12 3D: co-formulated ABT-450/r/ombitasvir, 150 mg/100 mg/25 mg QD; dasabuvir, 250 mg BID RBV: mg daily according to body weight (<75 kg and >75kg, respectively) SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

47 SVR12, % Patients SAPPHIRE-I Results: ITT SVR12 Rates % 95.3% 98.0% Superiority threshold The ITT SVR12 rate of 98.0% (95% CI, ) in GT1b-infected patients is superior to a calculated historical SVR12 control rate of 80% (95% CI, ) / / /151 All Patients GT1a GT1b SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

48 SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

49 SAPPHIRE-I: Adverse Events Occurring in >10% of Patients in Either Group Event, n (%) 3D + RBV (N=473) Placebo (N=158) P Value Any AE 414 (87.5) 116 (73.4) <0.05 Fatigue 164 (34.7) 45 (28.5) NS Headache 156 (33.0) 42 (26.6) NS Nausea 112 (23.7) 21 (13.3) <0.05 Pruritus 80 (16.9) 6 (3.8) <0.05 Insomnia 66 (14.0) 12 (7.6) <0.05 Diarrhea 65 (13.7) 11 (7.0) <0.05 Asthenia 57 (12.1) 6 (3.8) <0.05 Rash 51 (10.8) 9 (5.7) NS AEs were generally mild. SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

50 SVR12, % Patients SAPPHIRE-II INF-Free 12 week Regimen ABT-450r/ABT-267, ABT333, RBV in Treatment-Experienced: ITT SVR12 Rates % 96.0% 96.7% Superiority threshold (77%) The ITT SVR12 rate of 96.7% (95% CI, ) in GT1b-infected patients is superior to a calculated historical SVR12 control rate of 71% (95% CI, 64-77) / / /123 All Patients GT1a GT1b SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

51 SVR12, % Patients SAPPHIRE-II Results: ITT SVR12 Rates >95% in All Prior Peginterferon/Ribavirin Response Groups % 100% 95.2% /86 65/65 139/146 Prior Relapse Prior Partial Response Prior Null Response SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

52 SVR12, % Patients TURQUOISE-II: Cirrhosis; Naïve or Treatment Experienced G1 ITT SVR12 Rates of 92% to 96% P= Superiority threshold: 54% Non-inferiority threshold: 43% / Weeks 3D + RBV 165/ Weeks 3D + RBV SAPPHIRE-I Phase 3 Study of ABT-450/r/Ombitasvir + Dasabuvir + RBV in Treatment-Naïve Adults With HCV GT 1 International Liver Congress April

53 Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection (ION) Mangia EASL 2014; Afdhal N et al. NEJM. 2014;on-line 4/12/14

54 Ledipasvir/Sofosbuvir With or Without Ribavirin for 12 or 24 Weeks in Treatment-Experienced Genotype 1 HCV-Infected Patients: The Phase 3 ION-2 Study Afdhal et al. EASL 2014; Afdhal N et al. NEJM. 2014;on-line 4/12/14

55 NIH SYNERGY: HCV Treatment Naïve G1 NPI-NS5A+/- NNPI or PI NPI+NS5B NPI+NS5B NNPI NPI+NS5B PI Kohli A, et al. CROI 2014 Abstract 27LB

56 Kohli A, et al. CROI 2014 Abstract 27LB NIH SYNERGY TRIAL

57 Interferon-Free Treatment HCV-HIV Co-infection Growing data that HIV Co-Infection is no longer a special population

58 PHOTON-1: Sofosbuvir +RBV HIV-Co-Infected Treatment Naïve with G1,2,3 Experienced G2/3 Sofosbuvir HCV NS5B nucleotide inhibitor 4-14% with cirrhosis 93-98% on ART Naggie S, et al CROI 2014 Abstract 26

59 PHOTON 1: SOF+RBV HIV/HCV SVR 12 and 24 Genotype 1 Genotype 2 Genotype 3 Naggie S, et al CROI 2014 Abstract 26

60 C-WORTHY: HIV/HCV G1 Naïve, Non-Cirrhotic MK-5172 (NS3/4A)+MK-8742 (NS5A)+/- RBV ART: raltegravir+two NRTIs for at least 8 weeks prior to enrollment Sulkowski M, et al. 21 st CROI. Abstract 654LB

61 C-WORTHY MK-5172 (NS3/4A)+MK-8742 (NS5A)+/- RBV On Treatment Response Rate Sulkowski M, et al. 21 st CROI. Abstract 654LB SVR4: 97% with RBV; 90% without RBV

62 % of patients with HCV RNA < LLOQ ERADICATE Study (NIAID, LDV/SOF) LDV/SOF STR for Treatment of HCV GT 1 Co-infected with HIV (Interim Analysis) Study Weeks N = 50 GT 1, TN, stable HIV disease ARV Untreated: LDV/SOF ARV Treated*: LDV/SOF SVR 4 SVR 12 Interim results ARV Untreated ARV Treated / 13 37/ 37 13/ 13 37/ 37 13/ 13 30/ 30 Week 4 Week 8 EOT SVR4 SVR8 SVR12 12/ 12 22/ 22 10/ 10 10/ 10 LDV/SOF STR was well tolerated with no discontinuations Osinusi A, EASL, 2014, O14 62

63 Drug Interactions Must Be Discussed Currently approved protease inhibitors have many potential drug interactions Coadministered may inhibit or induce various metabolic pathways (eg, CYP3A, P-gp) Solutions may be found for virtually all potential drug-drug interactions

64 Concentration Drug-drug Interactions (DDIs) with Current PIs Drug interactions may affect blood levels of either PI or co-administered drug Drug + PI PI blocks the function of the CYP enzyme P Time PI (acting as inhibitor) may AUC of drug Drug acting as inducer may AUC of PI AUC=area under the curve Caution is needed with ALL co-administered medications Review package inserts for interaction lists Reconcile patient medication list Patient needs to communicate new meds started by other health care providers Other resource:

65 Summary SVR decreases liver and all-cause mortality HIV/HCV co-infection increases risk for hepatic deompensation SVR rates for HIV/HCV are comparable to mono-infection SMV and SOF will offer more treatment options for many patients Highly effective all-oral therapies are anticipated in the new future

66 Thank you!?

67 Activity Code FA376