High Cure Rates for Hepatitis C Virus Genotype 6 in Advanced Liver Fibrosis With 12 Weeks Sofosbuvir and Daclatasvir: The Vietnam SEARCH Study

Abstract

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.

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for hepatitis C in a single-arm mechanistic pilot study

“…Of 455 patients screened, 52 were enrolled and 1 subsequently withdrew ( Figure 2 ). Most exclusions were on account of either a FibroScan score of >7.1 kPa (with cirrhotic patients enrolled into a parallel study; Flower et al, 2021 ), or ineligible genotype.…”

Efficacy of ultra-short, response-guided sofosbuvir and daclatasvir therapy for Hepatitis C: a single arm mechanistic pilot study

“…Of 455 patients screened, 52 were enrolled and one subsequently withdrew (figure 2). Most exclusions were on account of a either a fibroscan score of >7.1kPa (with cirrhotic patients enrolled into a parallel study 35 ),or ineligible genotype.…”

Treatment Response and Drug Resistance Profiling of Genotype 6 of Hepatitis C Virus in HCV/HIV Co-Infected Patients: A Pilot Study from INDIA

“…In addition, Michaluk et al demonstrated that SVR attained in HCV GT4 mono-infected patients did not differ significantly from HCV/HIV co-infected patients, underlining the safety and effectiveness of current DAA therapy for HCV/HIV co-infected patients [ 23 ]. A study by Flower et al demonstrated no contribution of RAS to treatment outcomes in a cohort in Vietnam where HCV GT6 was predominant [ 24 ]. Although the existence of RAS (NS5a region) at the baseline did not influence the attainment of SVR in our analysis, we need large sample size studies to draw firm confirmations on the impact of BL-RAS on treatment response in HCV GT6 infected patients.…”