HCV TREATMENT

Surveying the Current Treatment Landscape

Several HCV treatments are currently available.

Sofosbuvir (Sovaldi®) is an NS5B nucleoside polymerase inhibitor that can suppress viral replication of all HCV genotypes. It has US Food and Drug Administration (FDA) approval for the treatment of genotypes 1 and 4 in combination with pegylated interferon and ribavirin, and for genotypes 2 and 3 in combination with ribavirin.

Simeprevir (Olysio®) is an NS3/4A protease inhibitor approved for the treatment of genotype 1a in combination with pegylated interferon and ribavirin. Ledipasvir (an NS5A inhibitor) and sofosbuvir (Harvoni®) are approved for the treatment of genotype 1.

The combination of ombitasvir, paritaprevir/ritonavir, and dasabuvir (Viekira Pak®) is approved for the treatment of patients with genotype 1 HCV, including those with compensated cirrhosis.

A combination of simeprevir and sofosbuvir also is FDA-approved for the treatment of genotype 1-infected patients.

Recently, the FDA approved new treatment options for genotypes 3 and 4. The combination of daclatasvir and sofosbuvir (Daklinza/Sovaldi®) is for the treatment of genotype 3-infected patients, and the combination of ombitasvir, paritaprevir, and ritonavir (Technivie®) with ribavirin is for the treatment of genotype 4-infected patients.

Treatment Recommendations

Current treatment recommendations for previously untreated patients with HCV infection, by genotype, are available at HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C.^[16]This website is continually updated as new drugs are approved and become available. Always consult the website for changes to recommendations before treating patients.

Treatment definitions used on the website include (1) recommended—favored for most patients; (2) alternative—optimal for a subset of patients; and (3) not recommended—inferior to other therapies.

At the time of this article's writing, the recommendations were as follows^[16]:

• Type 1a—three treatments: 
  • Daily fixed-dose combination of ledipasvir and sofosbuvir for 12 weeks;
  • Daily fixed-dose combination of paritaprevir/ombitasvir/ritonavir plus twice-daily dasabuvir, coupled with weight-based ribavirin, for 12 weeks in the absence of cirrhosis and 24 weeks if cirrhosis is present; or
  • Daily sofosbuvir plus simeprevir with or without weight-based ribavirin for 12 weeks in the absence of cirrhosis and 24 weeks if cirrhosis is present
• Type 1b—three treatments: 
  • Daily fixed-dose combination of ledipasvir and sofosbuvir for 12 weeks;
  • Daily fixed-dose combination of paritaprevir/ombitasvir/ritonavir plus twice-daily dasabuvir for 12 weeks in the absence of cirrhosis, and these same drugs with the addition of weight-based ribavirin for 24 weeks in the presence of cirrhosis; or
  • Daily sofosbuvir plus simeprevir for 12 weeks in the absence of cirrhosis and 24 weeks if cirrhosis is present
• Type 2: 
  • Daily sofosbuvir and weight-based ribavirin for 12 weeks in the absence of cirrhosis and for 24 weeks if cirrhosis is present
• Type 3: 
  • Daily sofosbuvir and weight-based ribavirin for 24 weeks;
  • Alternative regimen: daily sofosbuvir and weight-based ribavirin plus weekly pegylated interferon for 12 weeks
• Type 4: 
  • Daily fixed-dose combination of ledipasvir and sofosbuvir for 12 weeks;
  • Daily fixed-dose combination of paritaprevir/ombitasvir/ritonavir with weight-based ribavirin for 12 weeks; or
  • Daily sofosbuvir and weight-based ribavirin for 24 weeks
  • Alternative regimens: 
    • Daily sofosbuvir and weight-based ribavirin plus weekly pegylated interferon for 12 weeks; or
    • Daily sofosbuvir and simeprevir with or without weight-based ribavirin for 12 weeks
• Type 5: 
  • Data are limited regarding the treatment of genotype 5 
    • Daily sofosbuvir and weight-based ribavirin plus weekly pegylated interferon for 12 weeks
    • Alternative regimen: weekly pegylated interferon plus daily weight-based ribavirin for 48 weeks
• Type 6: 
  • Data are limited regarding the treatment of genotype 6 
    • Daily ledipasvir plus sofosbuvir for 12 weeks
    • Alternative regimen: daily sofosbuvir and weight-based ribavirin plus weekly pegylated interferon

Common side effects of oral direct-acting antiviral drugs include fatigue, nausea, headache, photosensitivity, rash, and insomnia. Anemia is more likely when the drugs are coupled with ribavirin.

Also, of note, a recent FDA drug safety communication described significant bradycardia occurring when patients use both amiodarone and sofosbuvir. The FDA recommended that sofosbuvir or sofosbuvir combinations not be administered to patients currently taking amiodarone.^[17]