title: Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, California. Electronic address: norah.terrault@ucsf.edu.
authors: Norah A
authors: NA
authors: Terrault
authors: Goethe University Hospital, Frankfurt, Germany.
authors: Stefan
authors: S
authors: Zeuzem
authors: Department of Medicine, Saint Louis University School of Medicine, St Louis, Missouri.
authors: Adrian M
authors: AM
authors: Di Bisceglie
authors: Yale University School of Medicine, New Haven, Connecticut.
authors: Joseph K
authors: JK
authors: Lim
authors: Liver Disease Center, Scripps Clinic, La Jolla, California.
authors: Paul J
authors: PJ
authors: Pockros
authors: Liver Wellness Center, Little Rock, Arkansas.
authors: Lynn M
authors: LM
authors: Frazier
authors: University of California San Diego, San Diego, California.
authors: Alexander
authors: A
authors: Kuo
authors: University of Michigan Health System, Ann Arbor, Michigan.
authors: Anna S
authors: AS
authors: Lok
authors: Liver Institute of Virginia, Richmond, Virginia.
authors: Mitchell L
authors: ML
authors: Shiffman
authors: Sheba Medical Center, Ramat Gan, Israel.
authors: Ziv
authors: Z
authors: Ben Ari
authors: University of North Carolina, Chapel Hill, North Carolina.
authors: Lucy
authors: L
authors: Akushevich
authors: University of North Carolina, Chapel Hill, North Carolina.
authors: Monika
authors: M
authors: Vainorius
authors: Johns Hopkins, Baltimore, Maryland.
authors: Mark S
authors: MS
authors: Sulkowski
authors: University of North Carolina, Chapel Hill, North Carolina.
authors: Michael W
authors: MW
authors: Fried
authors: University of Florida, Gainesville, Florida.
authors: David R
authors: DR
authors: Nelson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001663:Bilirubin / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D000069474:Sofosbuvir; D000072230:Sustained Virologic Response; D013997:Time Factors; D017211:Treatment Failure; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D054328:Proton Pump Inhibitors; D012709:Serum Albumin; C000595958:ledipasvir, sofosbuvir drug combination; D012254:Ribavirin; D014542:Uridine Monophosphate; D001663:Bilirubin; D000069474:Sofosbuvir
keywords: Antiviral; DAA; NS5A Inhibitor; NS5B Inhibitor