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

• Published in: PloS one Vol. 14; no. 8; p. e0221231
• Main Authors: Pérez, Ana Belén, Chueca, Natalia, Macías, Juan, Pineda, Juan Antonio, Salmerón, Javier, Rivero-Juárez, Antonio, Hidalgo-Tenorio, Carmen, Espinosa, María Dolores, Téllez, Francisco, Von-Wichmann, Miguel Ángel, Omar, Mohamed, Santos, Jesús, Hernández-Quero, José, Antón, José Joaquin, Collado, Antonio, Lozano, Ana Belén, García-Deltoro, Miguel, Casado, Marta, Pascasio, Juan Manuel, Selfa, Aida, Rosales, José Miguel, De la Iglesia, Alberto, Arenas, Juan Ignacio, García-Bujalance, Silvia, Ríos, María José, Bernal, Enrique, Martínez, Onofre, García-Herola, Antonio, Vélez, Mónica, Rincón, Pilar, García, Federico
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.08.2019; Public Library of Science (PLoS)
• Subjects: Amides; Analysis; Antimicrobial agents; Antiviral agents; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Benzofurans - therapeutic use; Biology and life sciences; Carbamates; Cyclopropanes; DNA sequencing; Dosage and administration; Drug resistance; Drug Resistance, Viral - genetics; Drug therapy; Effectiveness; Female; Gastroenterology; Genotype; Genotype & phenotype; Genotypes; Hepacivirus - genetics; Hepacivirus - pathogenicity; Hepatitis; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - epidemiology; Hepatitis C, Chronic - genetics; Hepatitis C, Chronic - virology; Hepatology; Humans; Imidazoles - therapeutic use; Infections; Infectious diseases; Liver cirrhosis; Liver diseases; Male; Medicine and health sciences; Middle Aged; Mutation; People and places; Physicians; Prevalence studies (Epidemiology); Quinoxalines - therapeutic use; Ribavirin; Ribavirin - therapeutic use; Sofosbuvir - therapeutic use; Spain - epidemiology; Sulfonamides; Sustained Virologic Response; Treatment outcome; Viral Nonstructural Proteins - genetics; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0221231

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.