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

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

The recommended first-line treatment regimens for HCV infection are pangenotypic direct-acting antiviral (DAA) combinations, specifically sofosbuvir/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8-12 weeks depending on cirrhosis status, regardless of HCV genotype. 1

Pangenotypic First-Line Options

Option 1: Sofosbuvir/Velpatasvir

• Dosing: Fixed-dose combination tablet (400 mg sofosbuvir/100 mg velpatasvir) once daily
• Duration: 12 weeks for all genotypes
• Patient populations:
  • Treatment-naïve patients without cirrhosis: 12 weeks without ribavirin
  • Treatment-naïve patients with compensated cirrhosis: 12 weeks without ribavirin (except genotype 3)
  • Treatment-experienced patients without cirrhosis: 12 weeks without ribavirin (except genotype 3)
  • Treatment-experienced patients with compensated cirrhosis: 12 weeks without ribavirin (except genotype 3)
  • Genotype 3 with compensated cirrhosis: 12 weeks with weight-based ribavirin or consider sofosbuvir/velpatasvir/voxilaprevir for 12 weeks 1

Option 2: Glecaprevir/Pibrentasvir

• Dosing: Fixed-dose combination (300 mg glecaprevir/120 mg pibrentasvir) once daily
• Duration:
  • Without cirrhosis: 8 weeks
  • With compensated cirrhosis: 12 weeks (8 weeks may be sufficient for treatment-naïve genotype 3 patients, but more data needed) 1

Genotype-Specific Considerations

Genotype 1

• Both pangenotypic regimens highly effective (>95% SVR)
• For genotype 1a with high baseline NS5A resistance, consider resistance testing if available 1

Genotype 2

• Excellent response to both pangenotypic regimens (>95% SVR) 1
• Alternative: Sofosbuvir/daclatasvir for 12 weeks without ribavirin 1

Genotype 3 (Most Difficult to Treat)

• Treatment-naïve without cirrhosis: Either pangenotypic regimen without ribavirin
• Treatment-experienced or with cirrhosis:
  • Sofosbuvir/velpatasvir with ribavirin for 12 weeks, or
  • Sofosbuvir/velpatasvir/voxilaprevir for 12 weeks, or
  • Glecaprevir/pibrentasvir for 16 weeks (treatment-experienced with cirrhosis) 1
• NS5A resistance testing recommended when available (Y93H mutation) 1

Genotypes 4,5, and 6

• Both pangenotypic regimens highly effective (>95% SVR) 1

Special Populations

Decompensated Cirrhosis

• Sofosbuvir/velpatasvir with ribavirin for 12 weeks 2
• Protease inhibitor-containing regimens (glecaprevir/pibrentasvir) contraindicated

HIV Co-infection

• Same regimens as HCV mono-infection
• Check for drug interactions with antiretroviral therapy 1

Common Pitfalls and Caveats

1. Resistance testing: Consider NS5A resistance testing before treatment for genotype 3 patients with cirrhosis when available 1

2. Drug interactions:

   • Acid-reducing agents can decrease velpatasvir absorption
   • Glecaprevir/pibrentasvir has numerous drug interactions with HIV medications
   • Always check for interactions before starting therapy

3. Ribavirin considerations:

   • Contraindicated in pregnancy
   • Requires dose adjustment in renal impairment
   • Monitor for anemia during treatment

4. Decompensated cirrhosis:

   • Avoid NS3/4A protease inhibitors (glecaprevir, voxilaprevir)
   • Use sofosbuvir-based regimens only

5. Infrequent HCV subtypes:

   • In patients from sub-Saharan Africa, China or South-East Asia, consider sequence analysis to identify uncommon subtypes that may have inherent resistance 1

The evolution of HCV treatment has dramatically improved outcomes with these pangenotypic regimens achieving SVR rates >95% across most patient populations with excellent safety profiles and short treatment durations 3, 4.