title: The cost-effectiveness of testing for NS5a resistance-associated polymorphisms at baseline in genotype 1a-infected (treatment-naïve and treatment-experienced) subjects treated with all-oral elbasvir/grazoprevir regimens in the United States.
abstract: The presence of baseline NS5A resistance-associated variants (RAVs) impacted treatment response in HCV genotype 1a (GT1a)-infected patients treated with elbasvir/grazoprevir (EBR/GZR) for 12 weeks, but not patients treated with EBR/GZR and ribavirin (RBV) for 16 weeks.
  
  
  
  To assess the cost-effectiveness of baseline testing for NS5A RAVs in EBR/GZR-treated patients compared without testing, and with current treatments for GT1a patients.
  
  
  
  We simulated the course of treatment with EBR/GZR, ledipasvir/sofosbuvir (LDV/SOF) and ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) with or without RBV and natural history of disease of GT1a patients. Treatment-related data from clinical trials were used in a state-transition model of the natural history of chronic HCV GT1a infection and liver disease to project lifetime costs (US$2015) and quality-adjusted life years (QALY). Other clinical and economic inputs were estimated from published sources. We conducted base case and sensitivity analyses.
  
  
  
  RAVs testing-guided treatment with EBR/GZR resulted in more QALYs than EBR/GZR without testing, 3D+RBV, or LDV/SOF8. This strategy was cost-saving relative to 3D+RBV or LDV/SOF8 and was cost-effective compared with EBR/GZR without testing. LDV/SOF12 was not cost-effective compared with the EBR/GZR RAVs testing-based strategy. Treatment with EBR/GZR guided by RAVs testing is the most effective regimen among treatment-experienced patients without cirrhosis and cirrhotic patients. In sensitivity analysis, RAVs testing was cost-effective in 48-55% and 63-85% among noncirrhotic and cirrhotic patients respectively.
  
  
  
  RAVs testing before treatment with EBR/GZR is likely to be a cost-effective alternative to the use of EBR/GZR without testing, LDV/SOF, or 3D among GT1a treatment-naïve or treatment-experienced patients.
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Elbasha
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: M N
authors.initials: MN
authors.lastname: Robertson
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Nwankwo
mesh_terms: D000284:Administration, Oral; D000577:Amides; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D001572:Benzofurans / Q000008:administration & dosage* / Q000009:adverse effects; D002219:Carbamates; D003362:Cost-Benefit Analysis; D003521:Cyclopropanes; D024882:Drug Resistance, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000821:virology; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011810:Quinoxalines / Q000008:administration & dosage* / Q000009:adverse effects; D013449:Sulfonamides; D014481:United States; D017361:Viral Nonstructural Proteins / Q000235:genetics*; D014773:Virology / Q000191:economics* / Q000379:methods; D047029:Lactams, Macrocyclic; D012324:RNA-Dependent RNA Polymerase
chemical_list: D000577:Amides; D000998:Antiviral Agents; D001572:Benzofurans; D002219:Carbamates; D003521:Cyclopropanes; D007093:Imidazoles; D011810:Quinoxalines; D013449:Sulfonamides; D017361:Viral Nonstructural Proteins; C578009:grazoprevir; D047029:Lactams, Macrocyclic; C000589335:elbasvir; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase