PLoS ONE (2019-01-01)

Prevalence of resistance associated substitutions and efficacy of baseline resistance-guided chronic hepatitis C treatment in Spain from the GEHEP-004 cohort.

  • Ana Belén Pérez,
  • Natalia Chueca,
  • Juan Macías,
  • Juan Antonio Pineda,
  • Javier Salmerón,
  • Antonio Rivero-Juárez,
  • Carmen Hidalgo-Tenorio,
  • María Dolores Espinosa,
  • Francisco Téllez,
  • Miguel Ángel Von-Wichmann,
  • Mohamed Omar,
  • Jesús Santos,
  • José Hernández-Quero,
  • José Joaquin Antón,
  • Antonio Collado,
  • Ana Belén Lozano,
  • Miguel García-Deltoro,
  • Marta Casado,
  • Juan Manuel Pascasio,
  • Aida Selfa,
  • José Miguel Rosales,
  • Alberto De la Iglesia,
  • Juan Ignacio Arenas,
  • Silvia García-Bujalance,
  • María José Ríos,
  • Enrique Bernal,
  • Onofre Martínez,
  • Antonio García-Herola,
  • Mónica Vélez,
  • Pilar Rincón,
  • Federico García

DOI
https://doi.org/10.1371/journal.pone.0221231
Journal volume & issue
Vol. 14, no. 8
p. e0221231

Abstract

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Treatment guidelines differ in their recommendation to determine baseline resistance associated substitutions (RAS) before starting a first-line treatment with direct-acting antivirals (DAAs). Here we analyze the efficacy of DAA treatment with baseline RAS information. We conducted a prospective study involving 23 centers collaborating in the GEHEP-004 DAA resistance cohort. Baseline NS5A and NS3 RASs were studied by Sanger sequencing. After issuing a comprehensive resistance report, the treating physician decided the therapy, duration and ribavirin use. Sustained virological response (SVR12) data are available in 275 patients. Baseline NS5A RAS prevalence was between 4.3% and 26.8% according to genotype, and NS3 RASs prevalence (GT1a) was 6.3%. Overall, SVR12 was 97.8%. Amongst HCV-GT1a patients, 75.0% had >800,000 IU/ml and most of those that started grazoprevir/elbasvir were treated for 12 weeks. In genotype 3, NS5A Y93H was detected in 9 patients. 42.8% of the HCV-GT3 patients that started sofosbuvir/velpatasvir included ribavirin, although only 14.7% carried Y93H. The efficacy of baseline resistance-guided treatment in our cohort has been high across the most prevalent HCV genotypes in Spain. The duration of the grazoprevir/elbasvir treatment adhered mostly to AASLD/IDSA recommendations. In cirrhotic patients infected with GT-3 there has been a high use of ribavirin.