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

AuthorsPérez, Ana Belén; Chueca, Natalia; Macias, Juan; Pineda, Juan A.; Salmerón, Javier; Rivero-Juárez, Antonio; Hidalgo-Tenorio, Carmen; Espinosa, María Dolores; Téllez, Francisco; von Wichman, Miguel A.; Omar, Mohamed; Santos, Jesús; Hernández Quero, José; Antón, José Joaquín; Collado, Antonio; Lozano, Ana Belén; García-Deltoro, Miguel; Casado, Marta ; Pascasio, Juan Manuel; Selfa, Aída; Rosales-Zábal, José Miguel; Iglesia, Alberto de la; Arenas, Juan Ignacio; García-Bujalance, Silvia; Ríos-Villegas, María José; Bernal-Morell, Enrique; Martínez-Madrid, Onofre; García-Herola, Antonio; Vélez, Mónica; Rincón, Pilar; García, Federico
Issue Date30-Aug-2019
PublisherPublic Library of Science
CitationPLoS ONE 14(8): e0221231 (2019)
AbstractTreatment 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.
Publisher version (URL)https://doi.org/10.1371/journal.pone.0221231
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