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  • Initial treatment for hepatitis C virus infection is usually successful, with about 95% cured
  • However, options are needed for people whose initial regimen failed
  • A fixed-dose combination of three drugs in one pill called Vosevi resulted in a retreatment cure rate of 96%

Until about 2015, treatment for chronic hepatitis C virus (HCV) infection consisted of a weekly injection of interferon-alpha. A course of treatment could last for up to 48 weeks. Interferon works indirectly against HCV by helping the immune system to destroy virus-infected cells. However, this treatment was only modestly effective and caused unpleasant and sometimes debilitating side effects.

In 2015, several combinations of antiviral drugs that target HCV became increasingly available in Canada and other high-income countries. These drugs are called direct-acting antivirals (DAAs). They are taken orally, usually once daily, for between eight and 12 weeks.

Clinical trials have found that treatment with DAAs is highly effective with rates of cure of 95% or more in many cases.

However, in a very small proportion of people, initial treatment with DAAs can fail. The reasons for such failure can vary from person to person and may involve at least the following factors:

  • the strain or genotype of HCV
  • the degree of liver injury
  • the regimen used
  • the presence of HCV that has developed resistance to some drugs

About Vosevi

Vosevi is the brand name of the following three anti-HCV drugs in one pill:

  • sofosbuvir
  • velpatasvir
  • voxilaprevir

As Vosevi contains three different drugs (most widely used HCV treatments contain two DAAs), it is generally reserved for people whose initial regimen of DAAs has failed to effect a cure.

In Canada

A team of leading Canadian doctors with experience caring for people with HCV cooperated in a study to explore the effectiveness of 12 consecutive weeks of Vosevi as an option for 128 participants whose previous regimen of DAAs had failed.

Overall, 96% of participants were cured with Vosevi.

Study details

Participants were enrolled in the Canadian Network Undertaking against HCV (CANUHC).

The average profile of the 128 participants at the start of the study was as follows:

  • age – 58 years
  • 80% men, 20% women
  • major genotypes of HCV: genotype 1 – 60%; genotype 2 – 3%; genotype 3 – 30%; genotype 4 – 5%; genotype 6 – 1%
  • coinfections – 7% had HCV and HIV; 2% had HCV and HBV; two people had all three viruses
  • body mass index (BMI) – 28
  • 44% had extensive scarring of the liver (cirrhosis)
  • 10% had symptoms of cirrhosis in the past
  • 19 people had a history of liver cancer with three people having a recurrence of liver cancer at the time of retreatment

Treatment history

Commonly used treatments in the past included the following:

  • Epclusa (sofosbuvir + velpatasvir) – 27%
  • Harvoni (sofosbuvir + ledipasvir) – 27%
  • Zepatier (elbasvir + grazoprevir) – 13%

Only 7% of participants had used more than one DAA regimen in the past.


Overall, 96% of participants (123 out of 128) were cured after a 12-week course of Vosevi.

All participants who had previously used Harvoni or Zepatier were cured when they were retreated with Vosevi.

Cure in subgroups

  • Out of 56 participants with cirrhosis, 95% (53) were cured.
  • There were 13 participants with a history of symptoms of cirrhosis prior to initiation of Vosevi. None of them experienced a recurrence of cirrhosis symptoms and 92% (12) were cured.
  • Ribavirin was added to the Vosevi regimen in 26 participants because they had used a combination of sofosbuvir and velpatasvir in the past or had complex DAA resistance and/or cirrhosis. However, the researchers stated that “no clear benefit of adding ribavirin was observed, with similar rates of [cure] with and without its use.”

Treatment failure

There were five people (4%) for whom Vosevi retreatment failed. According to the researchers, people whose retreatment failed tended to have “at least two of the following factors”:

  • HCV genotype 3 (this genotype may not always be responsive to treatment)
  • the presence of cirrhosis
  • previous liver transplant
  • past treatment with a combination of sofosbuvir + velpatasvir
  • complex combinations of HCV resistance mutations

Side effects and complications

No serious side effects were reported and none of the participants prematurely discontinued Vosevi because of side effects or the development of symptoms of cirrhosis.

Bear in mind

This Canadian study confirms the high effectiveness of Vosevi outside of clinical trials. Note that participants were selected because of their past history of treatment failure, so Vosevi had a very high barrier to overcome. Although the vast majority of people treated with DAAs as first-line therapy for HCV will be cured, there will be a few for whom first-line treatment will fail. As more physicians gain experience with Vosevi, a better understanding of the reasons why a small minority of people are not cured with it will emerge.

—Sean R. Hosein


Hepatitis C: An In-Depth Guide – CATIE

Understanding Cirrhosis of the Liver: First steps for the newly diagnosed – CATIE, Canadian Association of Hepatology Nurses (CAHN)

Trends in liver cancer among HIV-positive people in North America – CATIE News

Study finds increased risk of hospitalization but not death in people with hepatitis C virus who have COVID-19 – CATIE News

Exploring the role of interventions to eliminate hepatitis C virus (HCV) in Montreal prisons – CATIE News

Vosevi (sofosbuvir + velpatasvir + voxilaprevir) – CATIE factsheet


Onofrio FQ, Cooper C, Borgia S, et al.  Salvage therapy with sofosbuvir/velpatasvir/voxilaprevir in DAA-experienced patients: Results from a Prospective Canadian Registry. Clinical Infectious Diseases. 2021; in press.