Related Experiment Video
Updated: Mar 2, 2026

Reverse Genetics to Engineer Positive-Sense RNA Virus Variants
Published on: June 9, 2022
Ledipasvir-Sofosbuvir Plus Ribavirin in Treatment-Naive Patients With Hepatitis C Virus Genotype 3 Infection: An
Jordan J Feld1, Alnoor Ramji2, Stephen D Shafran3
1Toronto Centre for Liver Disease, University of Toronto, Ontario.
Insights
Treatment with ledipasvir-sofosbuvir and ribavirin achieved a high sustained virologic response (SVR12) in treatment-naive patients with genotype 3 hepatitis C virus (HCV). This regimen demonstrated good tolerability and efficacy, particularly in patients without cirrhosis.
Area of Science:
- Hepatology
- Virology
- Clinical Trials
Background:
- Genotype 3 hepatitis C virus (HCV) infection is associated with more rapid disease progression.
- Genotype 3 HCV is less responsive to current direct-acting antiviral therapies.
- Ledipasvir and sofosbuvir are direct-acting antivirals used in HCV treatment.
Purpose of the Study:
- To evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin.
- To assess treatment outcomes in patients with genotype 3 HCV infection.
- To determine sustained virologic response rates at 12 weeks post-treatment (SVR12).
Main Methods:
- An open-label, multicenter trial (NCT02413593) enrolled treatment-naive patients with genotype 3 HCV.
- All patients received 12 weeks of ledipasvir-sofosbuvir (90 mg/400 mg) plus weight-based ribavirin.
- Sustained virologic response 12 weeks after treatment (SVR12) was the primary endpoint.
Main Results:
- 99 of 111 (89%) patients achieved SVR12.
- Patients without cirrhosis had a higher SVR12 rate (94%) compared to those with compensated cirrhosis (79%).
- Common adverse events included fatigue (51%), headache (36%), and nausea (23%). No treatment-emergent resistance mutations were observed.
Conclusions:
- 12 weeks of ledipasvir-sofosbuvir plus ribavirin is effective in treatment-naive patients with genotype 3 HCV.
- The regimen demonstrated a high SVR rate, especially in patients without cirrhosis.
- The treatment was generally safe and well-tolerated.
Background:
Patients chronically infected with genotype 3 hepatitis C virus (HCV) have faster disease progression and are less responsive to current direct-acting antiviral regimens than patients infected with other genotypes. We conducted an open-label trial to evaluate the safety, tolerability, and efficacy of ledipasvir and sofosbuvir plus ribavirin in patients with genotype 3 HCV infection.
Methods:
We enrolled treatment-naive patients with and without compensated cirrhosis at 15 sites in Canada. All patients were treated with ledipasvir-sofosbuvir (90 mg and 400 mg) plus weight-based ribavirin for 12 weeks. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Secondary endpoints included evaluation of baseline and treatment-emergent drug resistance.
Results:
Of the 111 patients enrolled, 105 (95%) had subtype 3a HCV and 39 (35%) had compensated cirrhosis. SVR12 was achieved by 99 of 111 patients (89%; 95% confidence interval, 82%-94%). Of the 39 patients with cirrhosis, 31 (79%) achieved SVR12, compared with 68 of 72 (94%) patients without cirrhosis. No treatment-emergent resistance mutations occurred in those who failed treatment. One patient discontinued treatment due to liver cancer and died 22 days after treatment discontinuation. The most common adverse events were fatigue (51%), headache (36%), and nausea (23%).
Conclusions:
In this multicenter trial involving treatment-naive patients with genotype 3 HCV, 12 weeks of ledipasvir-sofosbuvir provided a high level of SVR in those without cirrhosis.
Clinical Trials Registration:
NCT02413593.
Related Concept Videos
Retrovirus Life Cycles
Subviral Agents
Diseases of the Liver and Gallbladder
Cirrhosis is characterized by the scarring of hepatic lobules in the liver, which are replaced by fibrous tissue, affecting the liver's normal functioning. NAFLD, on the other hand, is caused by an excessive build-up of fat in the liver, not...
Nephrotic Syndrome III : Nursing Management
Retroviruses
Chronic Pancreatitis II: Collaborative Care
Assessment:

