Effectiveness of sofosbuvir based direct-acting antiviral regimens for chronic hepatitis C virus genotype 6 patients: Real-world experience in Vietnam

PLoS One. 2020 May 20;15(5):e0233446. doi: 10.1371/journal.pone.0233446. eCollection 2020.

Abstract

Background: Hepatitis C virus (HCV) genotype 6 is the commonest cause of chronic hepatitis C infection in much of southeast Asia, but data on the effectiveness of direct-acting antiviral agents (DAAs) against this genotype are limited. We conducted a retrospective cohort study of patients attending the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam, to define the effectiveness of DAAs in the treatment of chronic HCV genotype 6 in actual practice.

Methods: We included all patients with genotype 6 infections attending our hospital between March 2016 and October 2017 who received treatment with sofosbuvir-based DAA treatment regimens, and compared their responses with those with genotype 1 infections.

Results: 1758 patients (1148 genotype 6, 65.4%; 610 genotype 1, 34.6%) were analyzed. The majority of patients (1480, 84.2%) received sofosbuvir/ledipasvir (SOF/LDV) ± ribavirin (RBV); 278 (15.8%) received sofosbuvir/Daclatasvir (SOF/DCV) ± RBV. The median age of the patients was 57 years, (interquartile range (IQR) 46-64 years) The baseline HCV viral load (log IU/ml) was significantly higher in patients infected with genotype 6 compared with those infected with genotype 1 (6.8, 5.3-6.6 versus 6.3, 5.3-6.5 log10 IU/ml, p = <0.001, Mann Whitney U test). A sustained virological response (SVR), defined as an undetectable viral load measured between 12 and 24 weeks after completing treatment, and indicating cure, was seen in 97.3% (1711/1758) of patients. Treatment failure, defined as HCV viral load ≥15 IU/ml ≥12 weeks after completing treatment appeared to be more frequent in patients infected with genotype 6 virus (3.2%, 37/1148) than in those infected with genotype 1 (1.7%, 10/610), p = 0.050 chi-squared test). We found no evidence that patient's age, gender, liver cirrhosis, diabetes, HBV or HIV coinfection, prior treatment failure with pegylated interferon therapy, body mass index (BMI), aspartate aminotransferase to platelet ratio index (APRI), or fibrosis 4 (FIB-4) index were associated with treatment failure.

Conclusions: Our study suggests that patients with HCV genotype 6 infection in Vietnam may respond less well to treatment with sofosbuvir based DAAs than patients with genotype 1 infections. Further studies are needed to confirm this observation and to define whether it is driven by genotype-specific mutations.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Benzimidazoles / therapeutic use
  • Fluorenes / therapeutic use
  • Genotype*
  • Hepacivirus / drug effects
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Middle Aged
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Sofosbuvir / administration & dosage*
  • Treatment Outcome
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / therapeutic use
  • Vietnam
  • Viral Load / drug effects
  • Viral Load / genetics

Substances

  • Antiviral Agents
  • Benzimidazoles
  • Fluorenes
  • ledipasvir, sofosbuvir drug combination
  • Ribavirin
  • Uridine Monophosphate
  • Sofosbuvir

Grants and funding

The author(s) received no specific funding for this work.