Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response

Gastroenterology. 2016 Dec;151(6):1131-1140.e5. doi: 10.1053/j.gastro.2016.08.004. Epub 2016 Aug 24.

Abstract

Background & aims: The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure.

Methods: We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12.

Results: The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (≥3.5 g/dL), lower total bilirubin (≤1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use.

Conclusions: Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

Keywords: Antiviral; DAA; NS5A Inhibitor; NS5B Inhibitor.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / administration & dosage
  • Benzimidazoles / therapeutic use*
  • Bilirubin / blood
  • Drug Therapy, Combination
  • Female
  • Fluorenes / administration & dosage
  • Fluorenes / therapeutic use*
  • Genotype
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Liver Cirrhosis / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Prospective Studies
  • Proton Pump Inhibitors / therapeutic use
  • Ribavirin / therapeutic use
  • Risk Factors
  • Serum Albumin / metabolism
  • Sustained Virologic Response*
  • Time Factors
  • Treatment Failure
  • Uridine Monophosphate / administration & dosage
  • Uridine Monophosphate / analogs & derivatives*
  • Uridine Monophosphate / therapeutic use
  • Young Adult

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • Proton Pump Inhibitors
  • Serum Albumin
  • ledipasvir, sofosbuvir drug combination
  • Ribavirin
  • Uridine Monophosphate
  • Bilirubin

Associated data

  • ClinicalTrials.gov/NCT01474811