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:2021:ofid/ofab267,
author = {Flower, B and McCabe, L and Le, Ngoc C and Le, Manh H and Le, Thanh P and Dang, Trong T and Vo, Thi T and Vu, Thi Kim H and Nguyen, Tat T and Phan, Thi Hong D and Nguyen, Thi Chau A and Dinh, Thi T and Tran, Thi Tuyet N and Tarning, J and Kingsley, C and Kestelyn, E and Pett, SL and Thwaites, G and Nguyen, Van VC and Smith, D and Barnes, E and Ansari, A and Turner, H and Rahman, M and Walker, AS and Day, J and Cooke, GS},
doi = {ofid/ofab267},
journal = {Open Forum Infectious Diseases},
title = {High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: the Vietnam SEARCH study},
url = {http://dx.doi.org/10.1093/ofid/ofab267},
volume = {8},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundGenotype 6 is the most genetically diverse lineage of hepatitis C virus (HCV), and predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the lowest costing treatment combination globally. In regional guidelines, longer treatment durations of SOF/DCV (24 weeks) are recommended for cirrhotic individuals, compared with other pangenotypic regimens (12 weeks), based on sparse data. Early on-treatment virological response may offer means of reducing length and cost of therapy in patients with liver fibrosis.MethodsIn this prospective trial in Vietnam, genotype 6-infected adults with advanced liver fibrosis or compensated cirrhosis were treated with SOF/DCV. Day 14 viral load was used to guide duration of therapy: participants with viral load <500 IU/ml at day 14 were treated with 12 weeks of SOF/DCV and those ≥500 IU/ml received 24 weeks. Primary endpoint was sustained virological response.FindingsOf 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a, 34% 6e. The remainder had 6h, 6k, 6l or 6o. 100% had viral load <500 IU/ml by day 14, meaning all received 12 weeks of SOF/DCV. 100% achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions (RAS) at baseline.Interpretation12 weeks of SOF/DCV achieves excellent cure rates in this population. This data supports the removal of costly genotyping in countries where genotype 3 prevalence in <5%, in keeping with WHO guidelines. NS5A-resistance associated mutations in isolation, do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.
AU  - Flower,B
AU  - McCabe,L
AU  - Le,Ngoc C
AU  - Le,Manh H
AU  - Le,Thanh P
AU  - Dang,Trong T
AU  - Vo,Thi T
AU  - Vu,Thi Kim H
AU  - Nguyen,Tat T
AU  - Phan,Thi Hong D
AU  - Nguyen,Thi Chau A
AU  - Dinh,Thi T
AU  - Tran,Thi Tuyet N
AU  - Tarning,J
AU  - Kingsley,C
AU  - Kestelyn,E
AU  - Pett,SL
AU  - Thwaites,G
AU  - Nguyen,Van VC
AU  - Smith,D
AU  - Barnes,E
AU  - Ansari,A
AU  - Turner,H
AU  - Rahman,M
AU  - Walker,AS
AU  - Day,J
AU  - Cooke,GS
DO  - ofid/ofab267
PY  - 2021///
SN  - 2328-8957
TI  - High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: the Vietnam SEARCH study
T2  - Open Forum Infectious Diseases
UR  - http://dx.doi.org/10.1093/ofid/ofab267
UR  - https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab267/6295331
UR  - http://hdl.handle.net/10044/1/89444
VL  - 8
ER  -
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