RT Journal Article
T1 Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals.
A1 Howe, Anita Y M
A1 Rodrigo, Chaturaka
A1 Cunningham, Evan B
A1 Douglas, Mark W
A1 Dietz, Julia
A1 Grebely, Jason
A1 Popping, Stephanie
A1 Sfalcin, Javier Alejandro
A1 Parczewski, Milosz
A1 Sarrazin, Christoph
A1 de Salazar, Adolfo
A1 Fuentes, Ana
A1 Sayan, Murat
A1 Quer, Josep
A1 Kjellin, Midori
A1 Kileng, Hege
A1 Mor, Orna
A1 Lennerstrand, Johan
A1 Fourati, Slim
A1 Di Maio, Velia Chiara
A1 Chulanov, Vladimir
A1 Pawlotsky, Jean-Michel
A1 Harrigan, P Richard
A1 Ceccherini-Silberstein, Francesca
A1 Garcia, Federico
K1 DAA
K1 DAA, direct-acting antiviral
K1 DCV, daclatasvir
K1 DSV, dasabuvir
K1 GT, genotype
K1 HCV
K1 LDV, ledipasvir
K1 NI, nucleoside
K1 NNI, non-nucleoside
K1 NS5A
K1 NS5AI, NS5A replication complex inhibitor
K1 OR, odds ratio
K1 PI, NS3 protease inhibitor
K1 PIB, pibrentasvir
K1 RAS
K1 RASs, resistance-associated substitutions
K1 SHARED, The Surveillance of Hepatitis C Antiviral Resistance, Epidemiology and methoDologies
K1 SOF, sofosbuvir
K1 SVR, sustained virologic response
K1 VEL, velpatasvir
K1 aOR, adjusted odds ratio
K1 sFC, substitution frequency change
K1 virologic failure
AB Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.
PB Elsevier BV
YR 2022
FD 2022-02-05
LK http://hdl.handle.net/10668/22315
UL http://hdl.handle.net/10668/22315
LA en
NO Howe AYM, Rodrigo C, Cunningham EB, Douglas MW, Dietz J, Grebely J, et al. Characteristics of hepatitis C virus resistance in an international cohort after a decade of direct-acting antivirals. JHEP Rep. 2022 Feb 24;4(5):100462.
DS RISalud
RD Apr 7, 2025