Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

Smith, David A.; Magrì, Andrea; Bowden, Rory; Chaturvedi, Nimisha; Fellay, Jacques; McLauchlan, John; Foster, Graham; Irving, William L.; Simmonds, Peter; Pedergnana, Vincent; Barnes, Eleanor; Ansari, Azim

doi:10.1101/2020.05.05.077230

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…The rs12979860 CC genotype is related to SVR with sofosbuvir and RBV treatment. 77,78 Patients with the rs12979860 CC genotype are less likely to have virologic relapse after receiving sofosbuvir/ ledipasvir or sofosbuvir/velpatasvir/voxilaprevir therapy. [79][80][81][82]…”

Section: Therapymentioning

confidence: 99%

The Knowledge on HCV: From the Discovery to the Elimination

Guan

Ren

Wang

et al. 2022

Infectious Microbes and Diseases

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From being described as "non-A, non-B" hepatitis in 1975 and being identified in 1989, to the emergence of direct-acting antiviral drugs (DAAs), knowledge on hepatitis C virus (HCV) has achieved a qualitative leap in recent decades. Although more than 95% of HCV patients can be cured by DAAs, the high detection rate, high treatment cost, and relative high recurrence rate for some subtypes (eg, type 3b) make it still a public health problem worldwide. Due to the widespread availability of DAAs, vaccine research has received relatively little attention. The purpose of this review is to look back to the discovery of the HCV, its life cycle, innate and adaptive immune responses, and the evolution of treatment options for HCV.

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Section: Therapymentioning

confidence: 99%

The Knowledge on HCV: From the Discovery to the Elimination

Guan

Ren

Wang

et al. 2022

Infectious Microbes and Diseases

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“…To evaluate the impact of HCV subtypes and resistance associated substitutions on treatment outcome, whole genome sequencing (WGS) was additionally performed on all enrolled participants' virus at baseline, and upon virological rebound and at start of retreatment in participants failing therapy. WGS of the HCV viral genome was attained using Illumina MiSeq platform as described previously [22][23][24][25] . The de novo assemblies nucleotide sequences were translated into amino acid and were aligned to H77 HCV reference (GenBank ID: NC_038882.1) and the NS5A and NS5B protein regions were extracted.…”

Section: Virus Sequencingmentioning

confidence: 99%

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for Hepatitis C: a single arm mechanistic pilot study

Flower

Hung

McCabe

et al. 2022

Preprint

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Background: WHO has called for research into predictive factors for selecting persons who could be successfully treated with shorter durations of direct acting antiviral (DAA) therapy for Hepatitis C. We evaluated early virological response as a means of shortening treatment and explored host, viral and pharmacokinetic contributors to treatment outcome. Methods: Duration of sofosbuvir and daclatasvir (SOF/DCV) was determined according to day 2 (D2) virologic response for HCV genotype (gt) 1- or 6-infected adults in Vietnam with mild liver disease. Participants received 4 or 8 weeks treatment according to whether D2 HCV RNA was above or below 500 IU/ml (standard duration is 12 weeks). Primary endpoint was sustained virological response (SVR12). Those failing therapy were retreated with 12 weeks SOF/DCV. Host IFNL4 genotype and viral sequencing was performed at baseline, with repeat viral sequencing if virological rebound was observed. Levels of SOF, its inactive metabolite GS-331007 and DCV were measured on day 0 and 28. Results: Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and one withdrew. SVR12 was achieved in 21/34 (62%) treated for 4 weeks, and 17/17 (100%) treated for 8 weeks. Overall 38/51 (75%) were cured with first-line treatment (mean duration 37 days). Despite a high prevalence of putative NS5A-inhibitor resistance associated substitutions (RAS), all first-line treatment failures cured after retreatment (13/13). We found no evidence treatment failure was associated with host IFNL4 genotype, viral subtype, baseline RAS or DCV levels. SOF metabolite levels were higher in those failing 4-week therapy. Conclusions: Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4 weeks treatment. Funding: Funded by the Medical Research Council (grant MR/P025064/1) and The Global Challenges Research Fund (Wellcome Trust Grant 206/296/Z/17/Z).) Clinical trial number: ISRCTN17100273

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Viral genome wide association study identifies novel hepatitis C virus polymorphisms associated with sofosbuvir treatment failure

Cited by 2 publications

References 36 publications

The Knowledge on HCV: From the Discovery to the Elimination

The Knowledge on HCV: From the Discovery to the Elimination

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for Hepatitis C: a single arm mechanistic pilot study

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