High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study
Background Genotype 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 we...
| প্রধান লেখক: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
Oxford University Press
2021
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| _version_ | 1826293221307711488 |
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| author | Flower, B McCabe, L Ngoc, CL Hung, LM Phuong, LT Trong, TD Thi, TV Kim, HVT Tat, TN Hong, DPT Chau, ANT Thi, TD Tuyet, NTT Tarning, J Kingsley, C Kestelyn, E Pett, SL Thwaites, G Chau, NVV Smith, D Barnes, E Ansair, A Turner, H Rahman, M Walker, AS Day, J Cooke, GS |
| author_facet | Flower, B McCabe, L Ngoc, CL Hung, LM Phuong, LT Trong, TD Thi, TV Kim, HVT Tat, TN Hong, DPT Chau, ANT Thi, TD Tuyet, NTT Tarning, J Kingsley, C Kestelyn, E Pett, SL Thwaites, G Chau, NVV Smith, D Barnes, E Ansair, A Turner, H Rahman, M Walker, AS Day, J Cooke, GS |
| author_sort | Flower, B |
| collection | OXFORD |
| description | Background
Genotype 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.
Methods
In 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.
Findings
Of 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.
Interpretation
12 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.
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| first_indexed | 2024-03-07T03:26:46Z |
| format | Journal article |
| id | oxford-uuid:b94bf1e7-beee-46f0-a7c7-584961a1f337 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:26:46Z |
| publishDate | 2021 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:b94bf1e7-beee-46f0-a7c7-584961a1f3372022-03-27T05:02:13ZHigh cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH StudyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b94bf1e7-beee-46f0-a7c7-584961a1f337EnglishSymplectic ElementsOxford University Press2021Flower, BMcCabe, LNgoc, CLHung, LMPhuong, LTTrong, TDThi, TVKim, HVTTat, TNHong, DPTChau, ANTThi, TDTuyet, NTTTarning, JKingsley, CKestelyn, EPett, SLThwaites, GChau, NVVSmith, DBarnes, EAnsair, ATurner, HRahman, MWalker, ASDay, JCooke, GSBackground Genotype 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. Methods In 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. Findings Of 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. Interpretation 12 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. |
| spellingShingle | Flower, B McCabe, L Ngoc, CL Hung, LM Phuong, LT Trong, TD Thi, TV Kim, HVT Tat, TN Hong, DPT Chau, ANT Thi, TD Tuyet, NTT Tarning, J Kingsley, C Kestelyn, E Pett, SL Thwaites, G Chau, NVV Smith, D Barnes, E Ansair, A Turner, H Rahman, M Walker, AS Day, J Cooke, GS High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study |
| title | High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study |
| title_full | High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study |
| title_fullStr | High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study |
| title_full_unstemmed | High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study |
| title_short | High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study |
| title_sort | high cure rates for hcv genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir the vietnam search study |
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