A One-Pill Regimen for All Patients with HCV Genotype 1 Infection

April 14, 2014

A One-Pill Regimen for All Patients with HCV Genotype 1 Infection

  1. Atif Zaman, MD, MPH

A simple daily regimen of sofosbuvir and ledipasvir is safe and effective, even in patients who previously failed therapy, patients with cirrhosis, and other difficult-to-treat populations.

  1. Atif Zaman, MD, MPH

The ideal treatment regimen for hepatitis C virus (HCV) infection would be interferon-free, simple (one pill a day would be best), and have high success rates in all genotypes and subpopulations (patients with cirrhosis, treatment-experienced patients) as well as minimal to no side effects. Recently, regimens combining sofosbuvir (a nucleotide polymerase inhibitor) and ledipasvir (an NS5A inhibitor) have successfully met most of those criteria in phase II studies of patients with HCV genotype 1 infection (NEJM JW Gastroenterol Nov 15 2013 and NEJM JW Gastroenterol Mar 28 2014). Now, phase III trial results are available.

In three industry-funded, randomized, open-label studies, investigators assessed the safety and efficacy of a single-pill, daily regimen of sofosbuvir (400 mg) and ledipasvir (90 mg) with and without ribavirin in different groups of patients with HCV genotype 1 infection.

In the trial by Kowdley and colleagues, 647 treatment-naive patients without cirrhosis were treated for 8 weeks with and without ribavirin or for 12 weeks without ribavirin. In two separate trials by Afdhal and colleagues, 865 treatment-naive patients with or without cirrhosis and 440 patients who previously failed peginterferon and ribavirin with or without a protease inhibitor (telaprevir or boceprevir) were treated for 12 or 24 weeks with or without ribavirin. Among the treatment-experienced population, 20% of patients had cirrhosis and 52% had been previously treated with a protease-based regimen.

Results were as follows:

  • In the treatment-naive population without cirrhosis, the sustained virologic response (SVR) rate at 12 weeks posttreatment (SVR12) was between 93% and 95% and similar regardless of treatment duration (8 or 12 weeks) or inclusion of ribavirin.

  • In the treatment-naive population with and without cirrhosis (16% with cirrhosis, 12% black), the SVR12 ranged from 97% to 99% regardless of length of treatment (12 or 24 weeks) or inclusion of ribavirin. Response rates were high (91% to 100%) even among patients with cirrhosis and black patients.

  • In the treatment-experienced population, SVR12 ranged from 94% to 99% regardless of duration of therapy (12 or 24 weeks) or inclusion of ribavirin. Compared with patients without cirrhosis, those with cirrhosis had numerically lower SVR rates with the 12-week regimens (82%–86%) but similar rates with the 24-week regimens (99%).

  • In all three studies, no treatment-related discontinuation occurred.


A single-pill, 12-week regimen should cure hepatitis C virus infection regardless of the subpopulation treated including patients who failed protease-based regimens. Some minor “tweaking” might remain, such as assessing whether some populations may benefit from 8 or 24 weeks of therapy or the addition of ribavirin, as these studies were not specifically powered to evaluate outcomes in subpopulations. However, the bottom line is that an extremely simple, safe, effective therapy for HCV genotype 1 infection is here.

Editor Disclosures at Time of Publication

  • Disclosures for Atif Zaman, MD, MPH at time of publication Nothing to disclose


Reader Comments (1)

Samuel Richardson MD Physician, Emergency Medicine, Correctional Medicine

The number of people who have Hep C in prisons is very high. From what I observe I doubt that most will be treated. Financial reasons mainly.in one state I estimate it would require half billion $ to treat the incarcerated population who have Hep C. I would Like to discover some means to treat these human beings. It would be the noble thing to do, but where would the money come from?

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