Imperial College London
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ProfessorGrahamCooke

Faculty of Medicine, Department of Infectious Disease

Vice Dean (Research); Professor of Infectious Diseases
 
 
 
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Contact

 

g.cooke

 
 
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Location

 

Infectious Diseases SectionMedical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Flower:2023:10.7554/eLife.81801,
author = {Flower, B and Hung, LM and Mccabe, L and Ansari, MA and Le, Ngoc C and Vo, Thi T and Vu, Thi Kim H and Nguyen, Thi Ngoc P and Phuong, LT and Quang, VM and Dang, Trong T and Le, Thi T and Nguyen, Bao T and Kingsley, C and Smith, D and Hoglund, RM and Tarning, J and Kestelyn, E and Pett, SL and van, Doorn R and Van, Nuil JI and Turner, H and Thwaites, GE and Barnes, E and Rahman, M and Walker, AS and Day, JN and Chau, NVV and Cooke, GS},
doi = {10.7554/eLife.81801},
journal = {eLife},
pages = {1--30},
title = {Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study.},
url = {http://dx.doi.org/10.7554/eLife.81801},
volume = {12},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: World Health Organization 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-week 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 days 0 and 28. RESULTS: Of 52 adults enrolled, 34 received 4 weeks SOF/DCV, 17 got 8 weeks and 1 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 (RASs), 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, SOF or DCV levels. CONCLUSIONS: Shortened SOF/DCV therapy, with retreatment if needed, reduces DAA use in patients with mild liver disease, while maintaining high cure rates. D2 virologic response alone does not adequately predict SVR12 with 4-week treatment. FUNDING: Funded by the Medical Research Council (Grant MR/P025064/1) and The Global Challenges Research 70 Fund (Wellcome Trust Grant 206/29
AU  - Flower,B
AU  - Hung,LM
AU  - Mccabe,L
AU  - Ansari,MA
AU  - Le,Ngoc C
AU  - Vo,Thi T
AU  - Vu,Thi Kim H
AU  - Nguyen,Thi Ngoc P
AU  - Phuong,LT
AU  - Quang,VM
AU  - Dang,Trong T
AU  - Le,Thi T
AU  - Nguyen,Bao T
AU  - Kingsley,C
AU  - Smith,D
AU  - Hoglund,RM
AU  - Tarning,J
AU  - Kestelyn,E
AU  - Pett,SL
AU  - van,Doorn R
AU  - Van,Nuil JI
AU  - Turner,H
AU  - Thwaites,GE
AU  - Barnes,E
AU  - Rahman,M
AU  - Walker,AS
AU  - Day,JN
AU  - Chau,NVV
AU  - Cooke,GS
DO  - 10.7554/eLife.81801
EP  - 30
PY  - 2023///
SN  - 2050-084X
SP  - 1
TI  - Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study.
T2  - eLife
UR  - http://dx.doi.org/10.7554/eLife.81801
UR  - https://www.ncbi.nlm.nih.gov/pubmed/36622106
UR  - https://elifesciences.org/articles/81801
UR  - http://hdl.handle.net/10044/1/102638
VL  - 12
ER  -
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