High cure rates for HCV genotype 6 in advanced liver fibrosis with 12 weeks sofosbuvir and daclatasvir: The Vietnam SEARCH Study

Journal article

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.

Authors: Flower, B; McCabe, L; Ngoc, CL; Hung, LM; Phuong, LT

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Open Forum Infectious Diseases
• Volume: 8
• Issue: 7
• Article number: ofab267
• Publication date: 2021-06-09
• Acceptance date: 2021-05-11
• DOI: 10.1093/ofid/ofab267
• EISSN: 2328-8957
• Language: English
• Keywords: FFR