What is the recommended first-line treatment regimen for Hepatitis C Virus (HCV) infection?

First-Line Treatment for Hepatitis C Virus (HCV) Infection

The recommended first-line treatment for Hepatitis C Virus (HCV) infection is either sofosbuvir/velpatasvir (400mg/100mg) once daily for 12 weeks or glecaprevir/pibrentasvir for 8 weeks (12 weeks in treatment-experienced patients with cirrhosis), regardless of HCV genotype (1-6). 1

Treatment Regimens Based on Patient Characteristics

For Treatment-Naïve Patients:

• Without cirrhosis:

  • Sofosbuvir/velpatasvir: 400mg/100mg once daily for 12 weeks 2
  • Glecaprevir/pibrentasvir: 300mg/120mg once daily for 8 weeks 3

• With compensated cirrhosis (Child-Pugh A):

  • Sofosbuvir/velpatasvir: 400mg/100mg once daily for 12 weeks 2
  • Glecaprevir/pibrentasvir: 300mg/120mg once daily for 8 weeks 3

• With decompensated cirrhosis (Child-Pugh B or C):

  • Sofosbuvir/velpatasvir + ribavirin for 12 weeks 2
  • Note: Protease inhibitors (including glecaprevir) should be avoided in decompensated cirrhosis due to risk of toxicity 1

For Treatment-Experienced Patients:

• Prior treatment with PegIFN/ribavirin (without cirrhosis):

  • Sofosbuvir/velpatasvir: 400mg/100mg once daily for 12 weeks 2
  • Glecaprevir/pibrentasvir: 300mg/120mg once daily for 8 weeks 3

• Prior treatment with PegIFN/ribavirin (with compensated cirrhosis):

  • Sofosbuvir/velpatasvir: 400mg/100mg once daily for 12 weeks 2
  • Glecaprevir/pibrentasvir: 300mg/120mg once daily for 12 weeks 3

• Prior treatment with NS5A inhibitor:

  • Glecaprevir/pibrentasvir: 300mg/120mg once daily for 16 weeks 3

• Prior treatment with NS3/4A protease inhibitor (without prior NS5A inhibitor):

  • Glecaprevir/pibrentasvir: 300mg/120mg once daily for 12 weeks 3

Efficacy of Recommended Regimens

Sofosbuvir/velpatasvir has demonstrated excellent efficacy across all genotypes:

• SVR12 rates of 99% (95% CI, 98 to >99) in patients with genotypes 1,2,4,5, and 6 4
• 95% SVR12 rate in HCV/HIV co-infected patients 5
• 97% overall SVR12 rate in Asian patients with diverse HCV genotypes 6

Glecaprevir/pibrentasvir has similarly shown high efficacy:

• High SVR rates across all genotypes with 8-week treatment in non-cirrhotic patients
• Effective for patients with prior treatment failure, including those with NS5A inhibitor experience 3

Special Populations

HCV/HIV Co-infection

• Use the same regimens as for HCV mono-infected patients 1
• Check for potential drug interactions with antiretroviral medications 1

Transplant Recipients

• For liver or kidney transplant recipients: Glecaprevir/pibrentasvir for 12 weeks 3
• For post-transplant patients with decompensated cirrhosis: Sofosbuvir/velpatasvir + ribavirin for 12 weeks 1

Patients with Renal Impairment

• Both sofosbuvir/velpatasvir and glecaprevir/pibrentasvir can be used without dose adjustment in patients with any degree of renal impairment, including those on dialysis 1

Important Considerations and Precautions

1. Test for HBV co-infection: All patients should be tested for current or prior HBV infection (HBsAg and anti-HBc) before starting treatment to prevent HBV reactivation 3, 2

2. Drug interactions:

   • Avoid proton pump inhibitors with sofosbuvir/velpatasvir
   • Avoid amiodarone with sofosbuvir-containing regimens due to risk of serious bradycardia 1
   • Check for interactions with HIV medications in co-infected patients

3. Ribavirin dosing: When required (e.g., decompensated cirrhosis), ribavirin should be dosed based on weight:

   • <75 kg: 1000 mg daily (divided twice daily)
   • ≥75 kg: 1200 mg daily (divided twice daily) 2

4. Monitoring: HCV RNA testing at 12 weeks post-treatment is recommended to confirm SVR12, with no routine HCV RNA monitoring required during treatment 1

These pangenotypic regimens have revolutionized HCV treatment by providing simple, highly effective options that work across all genotypes with minimal side effects, leading to cure rates exceeding 95% in most patient populations.