High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study.
cirrhosis
direct-acting antivirals
genotype 6
hepatitis C
response-guided therapy
Journal
Open forum infectious diseases
ISSN: 2328-8957
Titre abrégé: Open Forum Infect Dis
Pays: United States
ID NLM: 101637045
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
31
03
2021
accepted:
16
06
2021
entrez:
2
8
2021
pubmed:
3
8
2021
medline:
3
8
2021
Statut:
epublish
Résumé
Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive 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. 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 (SVR). Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline. Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.
Sections du résumé
BACKGROUND
BACKGROUND
Genotype 6 is the most genetically diverse lineage of hepatitis C virus, and it predominates in Vietnam. It can be treated with sofosbuvir with daclatasvir (SOF/DCV), the least expensive 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
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 (SVR).
RESULTS
RESULTS
Of 41 individuals with advanced fibrosis or compensated cirrhosis who commenced treatment, 51% had genotype 6a and 34% had 6e. The remainder had 6h, 6k, 6l, or 6o. One hundred percent had viral load <500 IU/mL by day 14, meaning that all received 12 weeks of SOF/DCV. One hundred percent achieved SVR12 despite a high frequency of putative NS5A inhibitor resistance-associated substitutions at baseline.
CONCLUSIONS
CONCLUSIONS
Prescribing 12 weeks of SOF/DCV results in excellent cure rates in this population. These data support the removal of costly genotyping in countries where genotype 3 prevalence is <5%, in keeping with World Health Organization guidelines. NS5A resistance-associated mutations in isolation do not affect efficacy of SOF/DCV therapy. Wider evaluation of response-guided therapy is warranted.
Identifiants
pubmed: 34337093
doi: 10.1093/ofid/ofab267
pii: ofab267
pmc: PMC8320300
doi:
Types de publication
Journal Article
Langues
eng
Pagination
ofab267Subventions
Organisme : Wellcome Trust
ID : 206296/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P025064/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R015600/1
Pays : United Kingdom
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
Références
Transplantation. 2018 Jan;102(1):119-126
pubmed: 28846559
Gastroenterology. 2018 Apr;154(5):1435-1448
pubmed: 29274866
Hepatol Int. 2016 Sep;10(5):681-701
pubmed: 27229718
Open Forum Infect Dis. 2019 Feb 22;6(3):ofz076
pubmed: 30949527
Hepatology. 2015 Apr;61(4):1127-35
pubmed: 25614962
F1000Res. 2015 Oct 13;4:1062
pubmed: 27092241
Can J Gastroenterol Hepatol. 2018 Nov 13;2018:3908767
pubmed: 30538973
Lancet Gastroenterol Hepatol. 2019 Feb;4(2):119-126
pubmed: 30552056
PLoS One. 2020 May 20;15(5):e0233446
pubmed: 32433676
Wellcome Open Res. 2019 Sep 6;4:132
pubmed: 31754636
Lancet Gastroenterol Hepatol. 2017 Nov;2(11):832-836
pubmed: 28802815
Liver Int. 2017 Sep;37(9):1314-1324
pubmed: 28177199
Can J Gastroenterol Hepatol. 2020 Jul 27;2020:8815829
pubmed: 32802821
Antivir Ther. 2017;22(3):263-269
pubmed: 27924779
J Hepatol. 2018 Aug;69(2):461-511
pubmed: 29650333
Antimicrob Agents Chemother. 2019 Mar 27;63(4):
pubmed: 30718256
Hepatology. 2020 Feb;71(2):686-721
pubmed: 31816111
J Clin Microbiol. 2016 Oct;54(10):2470-84
pubmed: 27385709
PLoS One. 2019 Mar 13;14(3):e0212734
pubmed: 30865664
Can J Gastroenterol Hepatol. 2020 Oct 31;2020:8872120
pubmed: 33194875
J Viral Hepat. 2020 Sep;27(9):886-895
pubmed: 32358826
J Hepatol. 2020 Nov;73(5):1170-1218
pubmed: 32956768
Lancet Gastroenterol Hepatol. 2016 Oct;1(2):97-104
pubmed: 27917405
Aliment Pharmacol Ther. 2019 Mar;49(5):492-505
pubmed: 30687952
Curr Hepat Rep. 2011 Jul 2;10(3):214-227
pubmed: 22180724
J Viral Hepat. 2019 Mar;26(3):316-322
pubmed: 30380166
J Acquir Immune Defic Syndr. 2017 May 1;75(1):97-107
pubmed: 28272163
Liver Int. 2018 Nov;38(11):1906-1910
pubmed: 30022590
BMC Bioinformatics. 2018 Dec 18;19(1):532
pubmed: 30563445
Viruses. 2019 Apr 03;11(4):
pubmed: 30987147
J Pediatr Gastroenterol Nutr. 2018 Mar;66(3):425-427
pubmed: 29135824
Mol Clin Oncol. 2020 Sep;13(3):1
pubmed: 32754315
Clin Transplant. 2018 Feb;32(2):
pubmed: 29193356
Open Forum Infect Dis. 2015 Mar 31;2(2):ofv043
pubmed: 26213689
Nat Rev Gastroenterol Hepatol. 2015 Aug;12(8):437-45
pubmed: 26122475