Resistance‐associated substitutions after sofosbuvir/velpatasvir/voxilaprevir triple therapy failure

García-Cehic, Damir; Rando, Ariadna; Rodríguez‐Frías, Francisco; Gregori, Josep; Costa, Juan García; Carrión, J.A.; Macenlle, Ramiro; Pamplona, Javier; Castro‐Iglesias, Ángeles; Cañizares, Angelina; Tabernero, David; Campos, Carolina; Buti, María; Esteban, Juan Ignacio; Quer, Josep

doi:10.1111/jvh.13497

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…High SVR rates have been reported in patients infected with "usual" HCV genotypes/subtypes in several studies, with no or modest impact of the presence of RASs at retreatment start on virological response. [30][31][32][33] RASs Y93H and C316N have been suggested to be associated with sofosbuvir/velpatasvir/voxilaprevir failures, [34] but this was not the case in our study. Overall, our results suggest that retreatment with sofosbuvir/velpatasvir/ voxilaprevir or with glecaprevir/pibrentasvir with or without sofosbuvir is efficacious in the vast majority of patients infected with "unusual" GT-1 subtypes who failed first-line therapy.…”

Section: Discussioncontrasting

confidence: 90%

Virological characterization of treatment failures and retreatment outcomes in patients infected with “unusual” HCV genotype 1 subtypes

et al. 2023

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Background and Aims: Suboptimal rates of sustained virological response have been reported in patients infected with an “unusual,” non-1a/1b HCV genotype 1 subtype. The objectives of this study were to assess the proportion of non-1a/1b genotype 1 subtypes in a population of HCV-infected patients who failed to achieve sustained virological response after first-line direct-acting antiviral treatment, to virologically characterize their failures and to assess their outcomes on retreatment. Approach and Results: Samples addressed between January 2015 and December 2021 to the French National Reference Center for Viral Hepatitis B, C, and D were prospectively analyzed by means of Sanger and deep sequencing. Among 640 failures, 47 (7.3%) occurred in patients infected with an “unusual” genotype 1 subtype. Samples were available in 43 of them; 92.5% of these patients were born in Africa. Our results show the presence at baseline and at treatment failure of NS3 protease and/or NS5A polymorphisms conferring inherent reduced susceptibility to direct-acting antivirals in these patients, together with the presence at failure of additional resistance-associated substitutions not naturally present as dominant species, but jointly selected by first-line therapy. Conclusions: Patients infected with “unusual” HCV genotype 1 subtypes are over-represented among direct-acting antiviral treatment failures. Most of them were born and likely infected in sub-Saharan Africa. “Unusual” HCV genotype 1 subtypes naturally carry polymorphisms that confer reduced susceptibility to the drugs currently used to cure hepatitis C, in particular the NS5A inhibitors. Retreatment with sofosbuvir plus an NS3 protease and an NS5A inhibitor is generally efficacious.

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Section: Discussioncontrasting

confidence: 90%

Virological characterization of treatment failures and retreatment outcomes in patients infected with “unusual” HCV genotype 1 subtypes

et al. 2023

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“…More recently, a test for resistance-associated substitutions (RAS) has been reported. Assessment of minority variants harboring RAS makes it possible to predict their selection with specific direct acting antivirals against HCV [ 63 , 134 ]. This allows for the creation of a final report for RAS that includes recommendations for re-treatment of patients refractory to the antiviral treatments [ 135 ].…”

Section: Ngs As a Diagnostic Toolmentioning

confidence: 99%

Next-Generation Sequencing for Confronting Virus Pandemics

Quer

Colomer-Castell

Campos

et al. 2022

Viruses

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Virus pandemics have happened, are happening and will happen again. In recent decades, the rate of zoonotic viral spillover into humans has accelerated, mirroring the expansion of our global footprint and travel network, including the expansion of viral vectors and the destruction of natural spaces, bringing humans closer to wild animals. Once viral cross-species transmission to humans occurs, transmission cannot be stopped by cement walls but by developing barriers based on knowledge that can prevent or reduce the effects of any pandemic. Controlling a local transmission affecting few individuals is more efficient that confronting a community outbreak in which infections cannot be traced. Genetic detection, identification, and characterization of infectious agents using next-generation sequencing (NGS) has been proven to be a powerful tool allowing for the development of fast PCR-based molecular assays, the rapid development of vaccines based on mRNA and DNA, the identification of outbreaks, transmission dynamics and spill-over events, the detection of new variants and treatment of vaccine resistance mutations, the development of direct-acting antiviral drugs, the discovery of relevant minority variants to improve knowledge of the viral life cycle, strengths and weaknesses, the potential for becoming dominant to take appropriate preventive measures, and the discovery of new routes of viral transmission.

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“…It is active against multiple genotypes and is also useful in re-treatment regimens ( Gane et al, 2016b , 2016c ; Jacobson et al, 2017a ; Lawitz et al, 2016 , 2017 ; Rodriguez-Torres et al, 2016 ). Mutations associated with drug therapy failure include Y56F for the G1b phenotype and A166T for the G3a phenotype ( Garcia-Cehic et al, 2021 ). The side effects include fatigue, headache, nausea, and diarrhea ( Heo and Deeks, 2018 ).…”

Section: Hepatitis C Virus (Hcv) and Antiviral Therapymentioning

confidence: 99%