Sofosbuvir-Velpatasvir: Treatment for Chronic Hepatitis C Virus Infection
Sofosbuvir-velpatasvir is a fixed-dose combination antiviral medication used to treat chronic hepatitis C virus (HCV) infection across all major genotypes (1,2,3,4,5, and 6) in adults and children 3 years of age and older. 1
Primary Indication
Sofosbuvir-velpatasvir is FDA-approved for treating chronic HCV infection in the following patient populations 1:
- Patients without cirrhosis or with compensated cirrhosis (Child-Pugh A) - administered as monotherapy for 12 weeks 2
- Patients with decompensated cirrhosis (Child-Pugh B or C) - administered in combination with ribavirin for 12 weeks 1
Genotype Coverage
This is a pangenotypic regimen, meaning it effectively treats all six major HCV genotypes 2:
- Genotype 1 (1a and 1b): Achieves 98-99% SVR12 rates in treatment-naïve and treatment-experienced patients with or without cirrhosis 2
- Genotype 2: Achieves 99-100% SVR12 rates across all patient populations 2
- Genotype 3: Achieves 98% SVR12 in treatment-naïve patients without cirrhosis; 89-93% in patients with cirrhosis or treatment-experienced patients 2
- Genotypes 4,5, and 6: Achieves 97-100% SVR12 rates 2
Dosing Regimen
The standard adult dose is 400 mg sofosbuvir plus 100 mg velpatasvir administered as a single tablet once daily 2:
- Treatment duration: 12 weeks for most patients 2
- Administration: Can be taken with or without food 1
- Pediatric dosing: Weight-based dosing for children 3 years and older, available as tablets or oral pellets 2, 1
Special Populations
Treatment-Experienced Patients
- Prior interferon/ribavirin failure: 12 weeks of sofosbuvir-velpatasvir without ribavirin achieves high SVR12 rates 2
- Genotype 3 with cirrhosis or treatment-experienced: Consider adding ribavirin or extending treatment based on NS5A resistance testing 2
HIV-HCV Coinfection
- Highly effective with SVR12 rates of 92-100% across genotypes 2
- Requires careful assessment of drug-drug interactions with antiretroviral therapy 2
Chronic Kidney Disease
- CKD Stage 5 on hemodialysis: Can be used safely with no dose adjustment, though glecaprevir/pibrentasvir is preferred first-line 3, 4
- Achieves high SVR12 rates despite 20-fold accumulation of sofosbuvir metabolite (GS-331007) 3
Pediatric Patients
- Approved for children 3 years and older 2, 1
- Ages 12-17 years: 95% SVR12 rate with adult dosing 2
- Ages 6-11 years: 93% SVR12 rate with weight-adjusted dosing 2
- Ages 3-5 years: 83% SVR12 rate with weight-adjusted dosing 2
Key Clinical Considerations
Resistance Testing for Genotype 3
- NS5A resistance-associated substitution Y93H is associated with lower response rates in genotype 3 patients with cirrhosis or prior treatment experience 2
- If Y93H is detected: Add ribavirin for 12 weeks 2
- If Y93H is absent: Treat with sofosbuvir-velpatasvir alone for 12 weeks 2
- If resistance testing unavailable: Add ribavirin to all treatment-experienced or cirrhotic genotype 3 patients 2
Critical Safety Warning
Hepatitis B reactivation can occur during or after HCV treatment with sofosbuvir-velpatasvir 1:
- Screen all patients for hepatitis B surface antigen and core antibody before initiating therapy 1
- Monitor at-risk patients during and after treatment 1
- Reactivation may cause severe liver injury, liver failure, or death 1
Drug-Drug Interactions
- Contraindicated with amiodarone due to risk of serious symptomatic bradycardia 1
- Avoid with rifampin, St. John's wort, and carbamazepine due to reduced sofosbuvir-velpatasvir levels 2
- Requires thorough interaction assessment before starting therapy, particularly in HIV-coinfected patients 2
Common Adverse Effects
The most frequently reported adverse events include 2, 5, 6, 7:
- Headache (most common across all age groups) 2, 5, 6
- Fatigue 5, 6, 7
- Nausea 5, 6, 7
- Vomiting (particularly in children) 2
The regimen is generally well tolerated with low discontinuation rates (<1%) and most adverse events being mild to moderate in severity 5, 6, 7.