Accelerating Drug Development Through Collaboration: The Hepatitis C Drug Development Advisory Group

Hutchison, Courtney; Kwong, Ann D.; Ray, Stuart C.; Struble, Kimberly; Swan, Tracy; Miller, Veronica

doi:10.1038/clpt.2014.113

Cited by 16 publications

(11 citation statements)

References 5 publications

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“…This review by the Drug Resistance Working Group of the Forum for Collaborative HIV Research's HCV Drug Development Advisory Group summarizes clinically relevant HCV DAA resistance data to provide a systematic review of all resistance information available from sponsors’ trials. This report is an update from a previously published version and includes DAAs approved by regulatory bodies in the United States, the European Union, and Japan as well as drugs in phase 3 clinical trials as of November 2014 .…”

Section: Mean Fold‐change In Resistance Compared To Wild‐type Replicomentioning

confidence: 99%

Hepatitis C virus drug resistance–associated substitutions: State of the art summary

et al. 2015

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Hepatitis C virus (HCV) drug development has resulted in treatment regimens composed of interferon‐free, all‐oral combinations of direct‐acting antivirals. While the new regimens are potent and highly efficacious, the full clinical impact of HCV drug resistance, its implications for retreatment, and the potential role of baseline resistance testing remain critical research and clinical questions. In this report, we discuss the viral proteins targeted by HCV direct‐acting antivirals and summarize clinically relevant resistance data for compounds that have been approved or are currently in phase 3 clinical trials. Conclusion: This report provides a comprehensive, systematic review of all resistance information available from sponsors’ trials as a tool to inform the HCV drug development field. (Hepatology 2015;62:1623–1632)

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Section: Mean Fold‐change In Resistance Compared To Wild‐type Replicomentioning

confidence: 99%

Hepatitis C virus drug resistance–associated substitutions: State of the art summary

et al. 2015

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“…Most of the patients who do not respond to DAA‐based treatment have viral strains with drug resistance. In fact, the high error rate of the HCV polymerase coupled with a very fast virion production (100‐fold higher than the human immunodeficiency virus) results in a complex mixture of naïve viral genetic populations (termed quasi‐species) pre‐existing treatment initiation . Several investigations detected resistance‐associated substitutions (RASs) at failure of an IFN‐free DAA regimen, and several questions regarding their prevalence and relevance in re‐treatment remain unanswered.…”

Section: Introductionmentioning

confidence: 99%

Virological patterns of HCV patients with failure to interferon‐free regimens

Starace

Minichini

Pascalis

et al. 2018

Journal of Medical Virology

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The study characterized the virological patterns and the resistance-associated substitutions (RASs) in patients with failure to IFN-free regimens enrolled in the real-life setting. All 87 consecutive HCV patients with failed IFN-free regimens, observed at the laboratory of the University of Campania, were enrolled. All patients had been treated with DAA regimens according to the HCV genotype, international guidelines, and local availability. Sanger sequencing of NS3, NS5A, and NS5B regions was performed at failure by home-made protocols. Of the 87 patients enrolled, 13 (14.9%) showed a misclassified HCV genotype, probably causing DAA failure, 16 had been treated with a sub-optimal DAA regimen, 19 with a simeprevir-based regimen and 39 with an optimal DAA regimen. A major RAS was identified more frequently in the simeprevir regimen group (68.4%) and in the optimal regimen group (74.4%) than in the sub-optimal regimen group (56.3%). The prevalence of RASs in NS3 was similar in the three groups (30.8-57.9%), that in NS5A higher in the optimal regimen group (71.8%) than in the sub-optimal regimen group (12.5%, P < 0.0001) and in the simeprevir regimen group (31.6%, P < 0.0005), and that in NS5B low in all groups (0-25%). RASs in two or more HCV regions were more frequently identified in the optimal regimen group (46.6%) than in the simeprevir-based regimen group (31.6%) and sub-optimal regimen group (18.7%). In our real-life population the prevalence of RASs was high, especially in NS3 and NS5A and in those treated with suitable DAA regimens.

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“…HCV-TARGET 7 ). It is clear from clinical trials in which RAVs were assessed via amplicon sequencing that the relevance of particular mutations depends on both the drug in question and the genetic background of the virus, and attempts have been made to summarise these data as more drugs enter clinical practice 8 .…”

Section: Introductionmentioning

confidence: 99%

ve-SEQ: Robust, unbiased enrichment for streamlined detection and whole-genome sequencing of HCV and other highly diverse pathogens

Bonsall

Ansari

et al. 2015

F1000Res

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The routine availability of high-depth virus sequence data would allow the sensitive detection of resistance-associated variants that can jeopardize HIV or hepatitis C virus (HCV) treatment. We introduce ve-SEQ, a high-throughput method for sequence-specific enrichment and characterization of whole-virus genomes at up to 20% divergence from a reference sequence and 1,000-fold greater sensitivity than direct sequencing. The extreme genetic diversity of HCV led us to implement an algorithm for the efficient design of panels of oligonucleotide probes to capture any sequence among a defined set of targets without detectable bias. ve-SEQ enables efficient detection and sequencing of any HCV genome, including mixtures and intra-host variants, in a single experiment, with greater tolerance of sequence diversity than standard amplification methods and greater sensitivity than metagenomic sequencing, features that are directly applicable to other pathogens or arbitrary groups of target organisms, allowing the combination of sensitive detection with sequencing in many settings.

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Accelerating Drug Development Through Collaboration: The Hepatitis C Drug Development Advisory Group

Cited by 16 publications

References 5 publications

Hepatitis C virus drug resistance–associated substitutions: State of the art summary

Hepatitis C virus drug resistance–associated substitutions: State of the art summary

Virological patterns of HCV patients with failure to interferon‐free regimens

ve-SEQ: Robust, unbiased enrichment for streamlined detection and whole-genome sequencing of HCV and other highly diverse pathogens

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