Recommended DAA Regimens

HCV Guideline Committee, May 2019

All regimens listed in this guideline were available as of May 2019.

These recommendations on treatment of chronic HCV were developed by the NYSDOH AI HCV Guideline Committee to guide primary care providers and other clinicians in NYS in treating patients with chronic HCV infection.

HIV/HCV coinfection: Treatment of chronic HCV infection in patients with HIV requires attention to drug-drug interactions between DAAs and antiretrovirals (ARVs) and to a few other HIV-specific treatment issues (see the Treatment of Patients with HIV/HCV Coinfection section of this guideline). Otherwise, clinicians should follow the recommendations below for treatment of patients with HCV monoinfection and consult a liver disease or experienced viral hepatitis specialist and an experienced HIV care provider as needed.

KEY POINTS: CHOOSING AN ANTI-HCV TREATMENT REGIMEN
  • Treatment regimen recommendations are organized according to HCV genotype and subtype, the presence or absence of compensated cirrhosis, and HCV treatment history.
  • The recommended regimens within each list are in alphabetical order, not in order of preference.
  • No single regimen is recommended over another within each list of options; data on direct comparisons of treatment regimens have not been published.
  • The choice of regimen should be based on individual pretreatment assessment findings, the general considerations detailed above, and insurance coverage.
  • The regimens recommended for retreatment are for patients who have been treated previously with DAAs or pegylated interferon (PEG-IFN) plus ribavirin (RBV).

Undetectable or indeterminate genotype: Rarely, laboratories report the results of an HCV genotype test as “undetectable” or “indeterminate” for a patient with detectable HCV viral load [Germer et al., 2011]. These findings are consistent with active HCV infection. The laboratory may be able to clarify the specific reason for the result; for example, an “undetectable” result may be due to the lower sensitivity of the genotype test compared with the HCV RNA test or a level of HCV RNA that is too low to perform the assay for genotype.

Data on treating patients with HCV who have an undetectable or indeterminate genotype are limited. All patients should be assessed for the degree of fibrosis. In terms of HCV treatment, one option is to repeat the genotype and HCV viral load tests in 3 months and then make a determination regarding the initiation of therapy. A second option is to offer these patients DAA therapy with a pan-genotypic regimen such as glecaprevir/pibrentasvir or sofosbuvir/velpatasvir at the same dose and duration recommended for treatment-naive patients with genotype 3 HCV infection, taking into consideration the degree of fibrosis (see Tables 19 and 20 > Genotype 3 in this guideline). At present, there are not sufficient data to offer ribavirin to these patients.

Recommended oral DAAs are listed in Table 7, below. All regimens listed in drug regimen tables for all HCV genotypes refer to oral medications.

Table 7: Recommended Oral Direct-Acting Antiviral Drugs and Drug Regimens
Drug/Combination Trade Name
Elbasvir/grazoprevir Zepatier
Glecaprevir/pibrentasvir Mavyret*
Ledipasvir/sofosbuvir Multiple brands
Sofosbuvir/velpatasvir Multiple brands
Sofosbuvir/velpatasvir/voxilaprevir Vosevi
*May 2019: The FDA has approved glecaprevir/pibrentasvir (Mavyret) for treatment of pediatric patients who are 12 years and older and weigh at least 45 kg. See the package insert for more information.
Reference

Germer J, Mandrekar J, Bendel J, et al. Hepatitis C virus genotypes in clinical specimens tested at a national reference testing laboratory in the United States. J Clin Microbiol 2011;49:3040-3043. [PMID: 21613437]

Genotype 1a

HCV Guideline Committee, May 2019

RECOMMENDATIONS
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 1a listed in Tables 8 through 11, below.
  • Clinicians should test for the presence of NS5A resistance-associated variants (RAVs) before starting therapy with elbasvir/grazoprevir in all patients with HCV genotype 1a infection. (A3)
  • If a regimen with weight-based ribavirin (RBV) is chosen, clinicians should dose as follows: (A1)
    • <75 kg: RBV 400 mg once daily plus 600 mg once daily (total daily dose: 1000 mg)
    • ≥75 kg: RBV 600 mg twice daily (total daily dose: 1200 mg)

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints) except where indicated. 

Table 8: Genotype 1a • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

8 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015; Lawitz et al. 2015; Sulkowski et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [Lawitz et al. 2015; Sulkowski et al. 2015; Zeuzem et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [FDA 2016]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks

For patients who are non-black, HIV-uninfected, and have HCV RNA <6 million copies/mL (Rating: A2): Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Kowdley et al. 2014, 2017; Terrault et al. 2016; FDA 2015]
(LED/SOF; multiple brands)

8 weeks

For patients who are black, HIV-infected, or have HCV RNA ≥6 million copies/mL: Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Kowdley et al. 2014, 2017; Terrault et al. 2016; FDA 2015]
(LED/SOF; multiple brands)

12 weeks

 

Table 9: Genotype 1a • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Gane et al. 2016]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Bourliere et al. 2015; Reddy et al. 2015]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [Lawitz et al. 2015; Zeuzem et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [FDA 2016]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks

 

Table 10: Genotype 1a • Prior failure with PEG-IFN* • No cirrhosis 

Choose 1 of the following regimens for retreatment (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

8 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Afdhal et al. 2014]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [Forns et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [Buti et al. 2016]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks
*Pegylated interferon plus ribavirin. 

 

Table 11: Genotype 1a • Prior failure with PEG-IFN plus RBV* • Compensated cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Bourliere et al. 2014, 2015]
(LED/SOF; multiple brands)

24 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily plus weight-based ribavirin twice daily [Bourliere et al. 2014, 2015]
(LED/SOF; multiple brands plus RBV; Copegus)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

Without baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily [Lawitz et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks
With baseline NS5A polymorphisms: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [FDA 2016]
(ELB/GRZ; Zepatier plus RBV; Copegus)
16 weeks

*Pegylated interferon plus ribavirin.

References

Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014;370(16):1483-93. [PMID: 24725238]

Bourliere M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015;15(4):397-404. [PMID: 25773757]

Bourliere M, Sulkowski M, Omata M, et al. An Integrated Safety and Efficacy Analysis of >500 Patients With Compensated Cirrhosis Treated With Ledipasvir/Sofosbuvir With or Without Ribavirin. 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014 Nov 7-11; Boston, MA. http://www.natap.org/2014/AASLD/AASLD_15.htm

Buti M, Gordon SC, Zuckerman E, et al. Grazoprevir, Elbasvir, and Ribavirin for Chronic Hepatitis C Virus Genotype 1 Infection After Failure of Pegylated Interferon and Ribavirin With an Earlier-Generation Protease Inhibitor: Final 24-Week Results From C-SALVAGE. Clin Infect Dis 2016;62(1):32-6. [PMID: 26371152]

FDA. Harvoni (ledipasvir and sofosbuvir) tablets, for oral use. 2015 Mar. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205834s024lbl.pdf [accessed 2019 May 9]

FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2019 May 9]

FDA. Zepatier (elbasvir and grazoprevir) tablets, for oral use. 2016 Jan. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208261Orig1s000lbl.pdf [accessed 2019 May 9]

Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]

Forns X, Gordon SC, Zuckerman E, et al. Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent. J Hepatol 2015;63(3):564-72. [PMID: 25895428]

Gane E, Poordad F, Wang S, et al. High Efficacy of ABT-493 and ABT-530 Treatment in Patients With HCV Genotype 1 or 3 Infection and Compensated Cirrhosis. Gastroenterology 2016;151(4):651-59.e1. [PMID: 27456384]

Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014;370(20):1879-88. [PMID: 24720702]

Kowdley KV, Sundaram V, Jeon CY, et al. Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection. Hepatology 2017;65(4):1094-103. [PMID: 28027579]

Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]

Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015;385(9973):1075-86. [PMID: 25467591]

Reddy KR, Bourliere M, Sulkowski M, et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology 2015;62(1):79-86. [PMID: 25846144]

Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015;385(9973):1087-97. [PMID: 25467560]

Terrault NA, Zeuzem S, Di Bisceglie AM, et al. Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016;151(6):1131-40.e5. [PMID: 27565882]

Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med 2015;163(1):1-13. [PMID: 25909356]

Genotype 1b

HCV Guideline Committee, May 2019

RECOMMENDATIONS
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 1b listed in Tables 12 through 15, below.
  • If a regimen with weight-based ribavirin (RBV) is chosen, clinicians should dose as follows: (A1)
    • <75 kg: RBV 400 mg once daily plus 600 mg once daily (total daily dose: 1000 mg)
    • ≥75 kg: RBV 600 mg twice daily (total daily dose: 1200 mg)

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed are rated A1 (strong recommendation, with high-quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints) except where indicated. 

Table 12: Genotype 1b • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (A1):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [Zeuzem et al. 2015; Lawitz et al. 2015; Sulkowski et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

8 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

For patients who are non-black, HIV-uninfected, and have HCV RNA <6 million copies/mL (Rating: A2): Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Kowdley et al. 2014, 2017; Terrault et al. 2016; FDA 2015]
(LED/SOF; multiple brands)  

8 weeks
For patients who are black, HIV-infected, or have HCV RNA ≥6 million copies/mL: Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Kowdley et al. 2014, 2017; Terrault et al. 2016; FDA 2015]
(LED/SOF; multiple brands)
12 weeks

Table 13: Genotype 1b • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (A1):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [Zeuzem et al. 2015; Lawitz et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Bourlier et al. 2015; Reddy et al. 2015]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

Table 14: Genotype 1b • Prior failure with PEG-IFN plus RBV* • No cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [Lawitz et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Poordad et al. 2017]
(GLE/PIB; Mavyret)

8 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Lawitz et al. 2014; Afdhal et al. 2014]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

*Pegylated interferon plus ribavirin.

Table 15: Genotype 1b • Prior failure with PEG-IFN plus RBV* • Compensated cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [Lawitz et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Bourliere et al. 2014, 2015]
(LED/SOF; multiple brands)

24 weeks
Ledipasvir 90 mg/sofosbuvir 400 mg once daily plus weight-based ribavirin twice daily [Bourliere et al. 2014, 2015]
(LED/SOF; multiple brands plus RBV; Copegus)
12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

*Pegylated interferon plus ribavirin.

References

Afdhal N, Reddy KR, Nelson DR, et al. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med 2014;370(16):1483-93. [PMID: 24725238]

Bourliere M, Bronowicki JP, de Ledinghen V, et al. Ledipasvir-sofosbuvir with or without ribavirin to treat patients with HCV genotype 1 infection and cirrhosis non-responsive to previous protease-inhibitor therapy: a randomised, double-blind, phase 2 trial (SIRIUS). Lancet Infect Dis 2015;15(4):397-404. [PMID: 25773757]

Bourliere M, Sulkowski M, Omata M, et al. An Integrated Safety and Efficacy Analysis of >500 Patients With Compensated Cirrhosis Treated With Ledipasvir/Sofosbuvir With or Without Ribavirin. 65th Annual Meeting of the American Association for the Study of Liver Diseases; 2014 Nov 7-11; Boston, MA. http://www.natap.org/2014/AASLD/AASLD_15.htm

FDA. Harvoni (ledipasvir and sofosbuvir) tablets, for oral use. 2015 Mar. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/205834s024lbl.pdf [accessed 2019 May 9]

FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2019 May 9]

Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]

Kowdley KV, Gordon SC, Reddy KR, et al. Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis. N Engl J Med 2014;370(20):1879-88. [PMID: 24720702]

Kowdley KV, Sundaram V, Jeon CY, et al. Eight weeks of ledipasvir/sofosbuvir is effective for selected patients with genotype 1 hepatitis C virus infection. Hepatology 2017;65(4):1094-103. [PMID: 28027579]

Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]

Lawitz E, Gane E, Pearlman B, et al. Efficacy and safety of 12 weeks versus 18 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin for hepatitis C virus genotype 1 infection in previously untreated patients with cirrhosis and patients with previous null response with or without cirrhosis (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015;385(9973):1075-86. [PMID: 25467591]

Lawitz E, Poordad FF, Pang PS, et al. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet 2014;383(9916):515-23. [PMID: 24209977]

Poordad F, Felizarta F, Asatryan A, et al. Glecaprevir and pibrentasvir for 12 weeks for hepatitis C virus genotype 1 infection and prior direct-acting antiviral treatment. Hepatology 2017;66(2):389-97. [PMID: 28128852]

Reddy KR, Bourliere M, Sulkowski M, et al. Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis. Hepatology 2015;62(1):79-86. [PMID: 25846144]

Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet 2015;385(9973):1087-97. [PMID: 25467560]

Terrault NA, Zeuzem S, Di Bisceglie AM, et al. Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response. Gastroenterology 2016;151(6):1131-40.e5. [PMID: 27565882]

Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med 2015;163(1):1-13. [PMID: 25909356]

Genotype 2

HCV Guideline Committee, May 2019

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 2 listed in Tables 16 through 18, below.

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints). 

Table 16: Genotype 2 • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017] 
(GLE/PIB; Mavyret)

8 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Foster et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

 

Table 17: Genotype 2 • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017] 
(GLE/PIB; Mavyret)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Foster et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

 

Table 18: Genotype 2 • Prior failure with PEG-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017] 
(GLE/PIB; Mavyret)

8 weeks 

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017] 
(GLE/PIB; Mavyret)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Foster et al. 2015] 
(SOF/VEL; multiple brands) 

12 weeks

*Pegylated interferon plus ribavirin.

References

Food and Drug Administration (FDA). Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2019 May 9]

Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015;373(27):2608-17. [PMID: 26575258]

Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]

Genotype 3

HCV Guideline Committee, May 2019

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 3 listed in Tables 19 through 22, below.

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints).

Sustained virologic response (SVR) rate: SVR rates are listed from studies of patients with HCV genotype 3 (reference numbers are cited in each table). These data have been included only for genotype 3 because, to date, achievement of an SVR in these patients, especially those with cirrhosis, has proven to be more difficult than it is in patients with other HCV genotypes.

Table 19: Genotype 3 • Treatment-naive • No cirrhosis

Choose 1 of the following regimens (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 83% to 94%) [FDA 2017]
(GLE/PIB; Mavyret)

8 weeks

Sofosbuvir 400/velpatasvir 100 mg once daily (SVR, 98%) [Foster et al 2015a]
(SOF/VEL; multiple brands)

12 weeks

 

Table 20: Genotype 3 • Treatment-naive • Compensated cirrhosis

Choose 1 of the following regimens (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 98%) [FDA 2017]
(GLE/PIB; Mavyret)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily (SVR, 93%) [Foster et al 2015a]
(SOF/VEL; multiple brands)

12 weeks

 

Table 21: Genotype 3 • Prior failure with Peg-IFN plus RBV* • No cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 98%) [FDA 2017]
(GLE/PIB; Mavyret)

16 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily (SVR, 91%) [Foster et al 2015a]
(SOF/VEL; multiple brands)

12 weeks

*Pegylated interferon plus ribavirin.

 

Table 22: Genotype 3 • Prior failure with PEG-IFN plus RBV* • Compensated cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

Glecaprevir 300 mg/pibrentasvir 120 mg once daily (SVR, 98%) [FDA 2017]
(GLE/PIB; Mavyret)

16 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily (SVR, 89%) [Foster et al. 2015b]
(SOF/VEL; multiple brands)

12 weeks

*Pegylated interferon plus ribavirin.

References

FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2019 May 9]

Foster GR, Pianko S, Brown A, et al. Efficacy of sofosbuvir plus ribavirin with or without peginterferon-alfa in patients with hepatitis C virus genotype 3 infection and treatment-experienced patients with cirrhosis and hepatitis C virus genotype 2 infection. Gastroenterology 2015(a);149(6):1462-70. [PMID: 26248087]

Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med 2015(b);373(27):2608-17. [PMID: 26575258]

Genotype 4

HCV Guideline Committee, May 2019

RECOMMENDATIONS
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 4 listed in Tables 23 and 24, below.
  • If a regimen with weight-based ribavirin (RBV) is chosen, clinicians should dose as follows: (A1)
    • <75 kg: RBV 400 mg once daily plus 600 mg once daily (total daily dose: 1000 mg)
    • ≥75 kg: RBV 600 mg twice daily (total daily dose: 1200 mg)

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints).

Table 23: Genotype 4 • Treatment-naive • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens (A1):

Duration

Elbasvir 50 mg/grazoprevir 100 mg once daily [Zeuzem et al. 2015]
(ELB/GRZ; Zepatier)

12 weeks

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Kohli et al. 2015; Abergel et al. 2016]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

 

Table 24: Genotype 4 • Prior failure with Peg-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

No cirrhosis: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [Zeuzem et al. 2015; FDA 2016]
(ELB/GRZ; Zepatier plus RBV; Copegus)

12 weeks

Compensated cirrhosis: Elbasvir 50 mg/grazoprevir 100 mg once daily plus weight-based ribavirin twice daily [Zeuzem et al. 2015; FDA 2016]
(ELB/GRZ; Zepatier plsu RBV; Copegus)

16 weeks

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Kohli et al. 2015]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

*Pegylated interferon plus ribavirin.

References

Abergel A, Asselah T, Metivier S, et al. Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. Lancet Infect Dis 2016;16(4):459-64. [PMID: 26803446]

Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]

FDA. Zepatier (elbasvir and grazoprevir) tablets, for oral use. 2016 Jan. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208261Orig1s000lbl.pdf [accessed 2019 May 9]

FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2019 May 9]

Kohli A, Kapoor R, Sims Z, et al. Ledipasvir and sofosbuvir for hepatitis C genotype 4: a proof-of-concept, single-centre, open-label phase 2a cohort study. Lancet Infect Dis 2015;15(9):1049-54. [PMID: 26187031]

Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]

Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial. Ann Intern Med 2015;163(1):1-13. [PMID: 25909356]

Genotype 5

HCV Guideline Committee, May 2019

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 5 listed in Tables 25 and 26, below.

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints).

Table 25: Genotype 5 • Treatment-naive • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens (A1):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Abergel et al. 2016]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

 

Table 26: Genotype 5 • Prior failure with PEG-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [Kwo et al. 2017; FDA 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Abergel et al. 2016]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

*Pegylated interferon plus ribavirin.

References

Abergel A, Asselah T, Metivier S, et al. Ledipasvir-sofosbuvir in patients with hepatitis C virus genotype 5 infection: an open-label, multicentre, single-arm, phase 2 study. Lancet Infect Dis 2016;16(4):459-64. [PMID: 26803446]

Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]

FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2019 May 9]

Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]

Genotype 6

HCV Guideline Committee, May 2019

RECOMMENDATION
  • Based on the results of the pretreatment assessment, clinicians should choose from among the treatment regimens for patients with HCV genotype 6 listed in Tables 27 and 28, below.

Recommended regimens: The recommendations are organized by previous HCV treatment (treatment-naive or treatment-experienced) and whether or not the patient has compensated cirrhosis. All drugs in the recommended regimens below are oral medications.

Drug names: Use of a “/” between two drug names indicates a co-formulated tablet. Use of the word “plus” indicates two separate drugs.

Rating of regimens: All regimen choices listed below are rated A1 (strong recommendation, with high quality evidence from at least 1 randomized trial with clinical outcomes and/or validated laboratory endpoints).

Table 27: Genotype 6 • Treatment-naive • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens (AI):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Gane et al. 2015]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands)

12 weeks

 

Table 28: Genotype 6 • Prior failure with PEG-IFN plus RBV* • No cirrhosis OR compensated cirrhosis

Choose 1 of the following regimens for retreatment (A1):

Duration

No cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

8 weeks

Compensated cirrhosis: Glecaprevir 300 mg/pibrentasvir 120 mg once daily [FDA 2017; Kwo et al. 2017]
(GLE/PIB; Mavyret)

12 weeks

Ledipasvir 90 mg/sofosbuvir 400 mg once daily [Gane et al. 2015]
(LED/SOF; multiple brands)

12 weeks

Sofosbuvir 400 mg/velpatasvir 100 mg once daily [Feld et al. 2015]
(SOF/VEL; multiple brands) 

12 weeks

*Pegylated interferon plus ribavirin.

References

FDA. Mavyret (glecaprevir and pibrentasvir) tablets, for oral use. 2017 Aug. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf [accessed 2017 Dec 19]

Feld JJ, Jacobson IM, Hezode C, et al. Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection. N Engl J Med 2015;373(27):2599-607. [PMID: 26571066]

Gane EJ, Hyland RH, An D, et al. Efficacy of ledipasvir and sofosbuvir, with or without ribavirin, for 12 weeks in patients with HCV genotype 3 or 6 infection. Gastroenterology 2015;149(6):1454-61.e1. [PMID: 26261007]

Kwo PY, Poordad F, Asatryan A, et al. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol 2017;67(2):263-71. [PMID: 28412293]