BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. METHODS: In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. RESULTS: A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. CONCLUSION: Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.
BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. METHODS: In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. RESULTS: A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. CONCLUSION: Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.
Authors: Jing Hong Loo; Wen Xin Flora Xu; Jun Teck Low; Wei Xuan Tay; Le Shaun Ang; Yew Chong Tam; Prem Harichander Thurairajah; Rahul Kumar; Yu Jun Wong Journal: World J Hepatol Date: 2022-06-27
Authors: Alessandra Mangia; Scott Milligan; Mandana Khalili; Stefano Fagiuoli; Stephen D Shafran; Fabrice Carrat; Denis Ouzan; George Papatheodoridis; Alnoor Ramji; Sergio M Borgia; Heiner Wedemeyer; Ruggero Losappio; Francisco Pérez-Hernandez; Nicole Wick; Robert S Brown; Pietro Lampertico; Karen Doucette; Ioanna Ntalla; Heribert Ramroth; Michael Mertens; Kim Vanstraelen; Juan Turnes Journal: Liver Int Date: 2020-06-09 Impact factor: 5.828
Authors: Peter Buggisch; Karsten Wursthorn; Albrecht Stoehr; Petar K Atanasov; Romain Supiot; Janet Lee; Jie Ting; Joerg Petersen Journal: PLoS One Date: 2019-04-04 Impact factor: 3.240
Authors: 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 Journal: PLoS One Date: 2019-08-30 Impact factor: 3.752
Authors: Elise J Smolders; Anouk M E Jansen; Peter G J Ter Horst; Jürgen Rockstroh; David J Back; David M Burger Journal: Clin Pharmacokinet Date: 2019-10 Impact factor: 6.447