Era of direct acting anti-viral agents for the treatment of hepatitis C

Table 1 Direct acting anti-viral agents with posology

No.	Trade name	Generic name with doses
1	Sovaldi	Sofosbuvir 400 mg
2	Olysio	Simeprevir 150 mg
3	Daklinza	Daclatasvir 30 mg/60 mg/90 mg
4	Harvoni	Ledipasvir 90 mg/Sofosbuvir 400 mg
5	Viekira Pak	1 d pack contains Paritaprevir 75 mg/Ombitasvir 12.5 mg/Ritonavir 50 mg tablet × 2 and Dasabuvir 250 mg tablet × 2
6	Viekira XR	Extended release tablet contains Dasabuvir 200 mg/ombitasvir 8.33 mg/Paritaprevir 50 mg/Ritonavir 33.33 mg
7	Technivie	Ombitasvir 12.5 mg/Paritaprevir 75 mg/Ritonavir 50 mg
8	Epclusa	Sofosbuvir 400 mg/ Velpatasvir 100 mg
9	Zepatier	Elbasvir 50 mg/ Grazoprevir 100 mg
10	Mavyret	Glecaprevir 100 mg/ Pibrentasvir 40 mg
11	Vosevi	Sofosbuvir 400 mg/Velpatasvir 100 mg/Voxilaprevir 100 mg

Table 2 Genotype 1a and 1b infection - treatment-naïve (with compensated cirrhosis) and non-cirrhotic

No.	First line therapy	Alternative regimen
Genotype 1a infection - treatment-naïve and non-cirrhotic
1	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk	Paritaprevir/ritonavir/ombitasvir and dasabuvir (in Viekira Pak and Viekira XR) with weight-based ribavirin - 12 wk
2	Elbasvir/Grazoprevir (Zepatier) for patients without baseline NS5A RAVs for Elbasvir - 12 wk	Simeprevir (Olysio) plus Sofosbuvir (Sovaldi) - 12 wk
3	Ledipasvir/Sofosbuvir (Harvoni) - 12 wk < Ledipasvir/Sofosbuvir (Harvoni) - 8 wk in non-black, HIV-uninfected individuals with serum HCV RNA < 6 million units/mL	Daclatasvir(Daklinza) plus Sofosbuvir (Sovaldi) - 12 wk
4	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk	Elbasvir/Grazoprevir (Zepatier) with weight-based ribavirin for patients with baseline NS5A RAVs for Elbasvir - 16 wk
Genotype 1a infection - treatment-naïve with compensated cirrhosis
1	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk	Elbasvir/Grazoprevir (Zepatier) with weight-based ribavirin for patients with baseline NS5A RASs for Elbasvir - 16 wk
2	Elbasvir/Grazoprevir (Zepatier) for patients without baseline NS5A RAVs for Elbasvir - 12 wk
3	Ledipasvir/Sofosbuvir (Harvoni) - 12 wk
4	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk
Genotype 1b infection - treatment-naïve and non-cirrhotic
1	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk	Paritaprevir/ritonavir/ombitasvir and dasabuvir (in Viekira Pak and Viekira XR) - 12 wk
2	Elbasvir/Grazoprevir (Zepatier) - 12 wk	Simeprevir (Olysio) plus Sofosbuvir (Sovaldi) - 12 wk
3	Ledipasvir/Sofosbuvir (Harvoni) - 12 wk < Ledipasvir/Sofosbuvir (Harvoni - 8 wk in non-black, HIV-uninfected individuals with serum HCV RNA < 6 million units/mL	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) - 12 wk
4	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk
Genotype 1b infection - treatment-naïve with compensated cirrhosis
1	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk	Paritaprevir/ritonavir/ombitasvir and dasabuvir (in Viekira Pak and Viekira XR) - 12 wk
2	Elbasvir/Grazoprevir (Zepatier - 12 wk
3	Ledipasvir/Sofosbuvir (Harvoni) - 12 wk
4	Sofosbuvir/Velpatasvir (Epclusa - 12 wk

RAVs: Resistance- associated variants; HIV: Human immunodeficiency virus; HCV: Hepatitis C virus.

Table 3 Genotype 1 infection-treatment-experienced

Glecaprevir/Pibrentasvir (Mavyret): Duration of treatment depends on previous regimen and presence or absence of compensated cirrhosis.
Previous regimen	No cirrhosis	Compensated cirrhosis
Pegylated IFN, ribavirin and/or Sofosbuvir but no prior exposure to NS3/4A PI or NS5A inhibitor	8 wk	12 wk
NS3/4A PI but no prior exposure to NS5A inhibitor	12 wk	12 wk
NS5A inhibitor but no prior exposure to NS3/4A PI	16 wk	16 wk
Elbasvir/Grazoprevir (Zepatier): Duration depends on viral load irrespective of no cirrhosis or compensated cirrhosis as per EASL guideline.
Previous regimen	HCV RNA ≤ 800000 IU/mL	HCV RNA > 800000 IU/mL
Pegylated IFN and ribavirin	12 wk without ribavirin	16 wk with ribavirin
Ledipasvir/Sofosbuvir (Harvoni): Applicable for both non-cirrhotics andcompensated cirrhotics.
Previous regimen	With ribavirin	Without ribavirin
PEG IFN and ribavirin	12 wk	24 wk
Sofosbuvir/Velpatasvir (Epclusa): Treatment is same for both non-cirrhotics and compensated cirrhotics.
Previous regimen	No cirrhosis	Compensated cirrhosis
PEG IFN and ribavirin	12 wk without ribavirin	12 wk without ribavirin
Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi): Applicable for both non-cirrhotics and compensated cirrhotics.
Previous regimen	With ribavirin	Without ribavirin
PEG IFN and ribavirin	12 wk	24 wk
Paritaprevir/ritonavir/ombitasvir and dasabuvir (in Viekira Pak and Viekira XR) with weight-based ribavirin.
Previous regimen	No cirrhosis	Compensated cirrhosis
PEG IFN and ribavirin	12 wk	24 wk

IFN: Interferon; PI; Protease inhibitors; HCV: Hepatitis C virus.

Table 4 Genotype 2-4 infection - treatment-naïve (with compensated cirrhosis) and non-cirrhotic

No.	First line therapy	Alternative regimen
Genotype 2 infection - treatment-naïve and non-cirrhotic
1	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk	Daclatasvir(Daklinza) plus Sofosbuvir (Sovaldi) - 12 wk
2	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk
Genotype 2 infection - treatment-naïve with compensated cirrhosis
1	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk	Daclatasvir(Daklinza) plus Sofosbuvir (Sovaldi) - 16 to 24 wk
2	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk
Genotype 3 infection - treatment-naïve and non- cirrhotic
1	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) - 12 wk
2	Sofosbuvir/Velpatasvir (Epclusa - 12 wk
Genotype 3 infection - treatment-naïve with compensated cirrhosis
1	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk	Vosevi - Sofosbuvir 400 mg/ Velpatasvir 100 mg/ Voxilaprevir 100 mg when Y93 is present - 12 wk
2	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) with or without weight-based ribavirin - 24 wk
Genotype 4 infection - treatment-naïve and non-cirrhotic
1	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk	Ombitasvir 25 mg/Paritaprevir 150 mg/ Ritonavir 100 mg (Technivie) with weight-based ribavirin - 12 wk
2	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk
3	Elbasvir/Grazoprevir (Zepatier) - 12 wk
4	Ledipasvir/Sofosbuvir (Harvoni) - 12 wk
Genotype 4 infection - treatment-naïve with compensated cirrhosis
1	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk	Ombitasvir 25 mg/Paritaprevir 150 mg/ Ritonavir 100 mg (Technivie) with weight-based ribavirin - 12 wk
2	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk
3	Elbasvir/Grazoprevir (Zepatier) - 12 wk
4	Ledipasvir/Sofosbuvir (Harvoni) - 12 wk

Table 5 Genotype 5 or 6 infection - treatment-naïve with and without compensated cirrhosis

No.	DAA	No cirrhosis	Compensated cirrhosis
1	Glecaprevir/Pibrentasvir (Mavyret)	8 wk	12 wk
2	Sofosbuvir/Velpatasvir (Epclusa)	12 wk	12 wk
3	Ledipasvir/Sofosbuvir (Harvoni)	12 wk	12 wk

DAA: Direct acting anti-viral agent.

Table 6 Genotype 2-6 infection - treatment-experienced

	First line therapy	Alternative regimen
Genotype 2 infection - treatment-experienced
Pegylated IFN/ribavirin-experienced without cirrhosis	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk or Sofosbuvir/Velpatasvir (Epclusa) - 12 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) - 12 wk
Pegylated IFN/ribavirin-experienced with compensated cirrhosis	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk or Glecaprevir/Pibrentasvir (Mavyret) - 12 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) - 16 to 24 wk
Sofosbuvir plus ribavirin-experienced with or without compensated cirrhosis	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk or Glecaprevir/Pibrentasvir (Mavyret) - 12 wk
Genotype 3 infection - treatment-experienced
Pegylated IFN/ ribavirin-experienced without cirrhosis	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) - 12 wk or Glecaprevir/Pibrentasvir (Mavyret) - 16 wk or Sofosbuvir/Velpatasvir/Voxilaprevir - 12 wk
Pegylated IFN/ ribavirin-experienced with compensated cirrhosis	Elbasvir/Grazoprevir (Zepatier) - 12 wk or Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi) -12 wk	Sofosbuvir/Velpatasvir (Epclusa) plus weight-based ribavirin - 12 wk or Glecaprevir/Pibrentasvir (Mavyret) - 16 wk
DAA-experienced including NS5A inhibitors with or without compensated cirrhosis	Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi) - 12 wk or in case of NS5A inhibitor failure and cirrhosis - Vosevi plus weight-based Ribavirin - 12 wk
Genotype 4 infection - treatment-experienced
Pegylated IFN/ ribavirin-experienced without cirrhosis	Sofosbuvir/Velpatasvir (Epclusa) -12 wk or Glecaprevir/Pibrentasvir (Mavyret) - 8 wk or Elbasvir/Grazoprevir (Zepatier) in virologic relapse - 12 wk or Ledipasvir/Sofosbuvir (Harvoni) - 12 wk	Ombitasvir 25 mg/Paritaprevir 150 mg/Ritonavir 100 mg plus weight based Ribavirin - 12 wk or Elbasvir/Grazoprevir (Zepatier) with weight-based Ribavirin (in case of prior on-treatment virologic failure) - 16 wk
Pegylated IFN/ ribavirin-experienced with compensated cirrhosis	Sofosbuvir/Velpatasvir (Epclusa) - 12 wk or Elbasvir/Grazoprevir (Zepatier) in virologic relapse - 12 wk or Glecaprevir/Pibrentasvir (Mavyret) - 12 wk	Ombitasvir 25 mg/Paritaprevir 150 mg/ Ritonavir 100 mg plus weight based Ribavirin - 12 wk or Elbasvir/Grazoprevir (Zepatier) with weight-based Ribavirin (in case of prior on-treatment virologic failure - 16 wk or Ledipasvir/Sofosbuvir (Harvoni) plus weight-based Ribavirin) - 12 wk
DAA-experienced including NS5A inhibitors with or without compensated cirrhosis	Sofosbuvir/Velpatasvir/Voxilaprevir (Vosevi) - 12 wk
Genotype 5 or 6 infection - treatment-experienced (recommended regimen)
Pegylated IFN/ ribavirin-experienced with or without compensated cirrhosis	Glecaprevir/Pibrentasvir (Mavyret) - 8 wk for patients without cirrhosis and 12 wk for patients with compensated cirrhosis or Ledipasvir/Sofosbuvir (Harvoni) plus weight-based Ribavirin - 12 wk or Sofosbuvir/Velpatasvir (Epclusa) - 12 wk
DAA-experienced including NS5A inhibitors with or without compensated cirrhosis	Sofosbuvir/Velpatasvir/ Voxilaprevir (Vosevi) - 12 wk

IFN: Interferon; DAA: Direct acting anti-viral agent.

Table 7 Recommended and alternative therapy

Genotype	Treatment-naïve and - experienced patients with HCV infection in the allograft without cirrhosis	Treatment-naïve and - experienced patients with HCV infection in the allograft with compensated cirrhosis	Treatment-naïve and - experienced patients with HCV infection in the allograft with decompensated cirrhosis
Recommended therapy
1, 4, 5 or 6	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk or Ledipasvir/Sofosbuvir (Harvoni) for 12 wk	Ledipasvir/Sofosbuvir (Harvoni) with weight-based ribavirin - 12 wk	Ledipasvir/Sofosbuvir (Harvoni) with initial low dose of ribavirin (600 mg), increase the dose as tolerated - 12 wk
2 or 3	Glecaprevir/Pibrentasvir (Mavyret) - 12 wk or Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) with initial low dose of ribavirin (600 mg), increase the dose as tolerated for 12 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) with initial low dose of ribavirin (600 mg), increase the dose as tolerated - 12 wk	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) with initial low dose of ribavirin (600 mg), increase the dose as tolerated for 12 wk or Sofosbuvir/Velpatasvir (Epclusa) with weight-based ribavirin - 12 wk
Alternative therapy
1, 4, 5 or 6	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) with initial low dose of ribavirin (600 mg), increase the dose as tolerated for 12 wk or HCV genotype 1 or 4 infection only: Simeprevir (Olysio) plus Sofosbuvir (Sovaldi) with or without weight-based ribavirin	Daclatasvir (Daklinza) plus Sofosbuvir (Sovaldi) with initial low dose of ribavirin (600 mg), increase the dose as tolerated for 12 wk or HCV genotype 1 or 4 infection only: Simeprevir (Olysio) plus Sofosbuvir (Sovaldi) with or without weight-based ribavirin
2 or 3		Glecaprevir/Pibrentasvir (Mavyret) for 12 wk or Sofosbuvir/Velpatasvir (Epclusa) with weight-based ribavirin for 12 wk

HCV: Hepatitis C virus.