On-treatment HCV RNA as a predictor of sustained virological response in HCV genotype 3-infected patients treated with daclatasvir and sofosbuvir.

Abstract

BACKGROUND AND AIMS:

Many currently available direct-acting antiviral (DAA) regimens are less effective against HCV genotype 3 than against other HCV genotypes. The all-oral, pangenotypic DAA combination of daclatasvir (NS5A inhibitor) + sofosbuvir (nucleotide NS5B inhibitor) was studied in genotype 3-infected treatment-naive and -experienced patients (ALLY-3) who achieved rates of sustained virological response at post-treatment Week 12 (SVR12) of 90 and 86% respectively. In this analysis, we assessed whether on-treatment responses to daclatasvir + sofosbuvir in genotype 3-infected patients could predict treatment outcome.

METHODS:

In ALLY-3, treatment-naive and -experienced patients, with or without cirrhosis, were treated with daclatasvir + sofosbuvir for 12 weeks. HCV RNA kinetics and categorical virological responses on treatment were assessed. The proportions of responders and nonresponders by study week, and time to first undetectable HCV RNA, were analysed for utility in predicting treatment outcome.

RESULTS:

Overall, HCV RNA levels declined rapidly during Week 1 of treatment in both treatment-naive and -experienced cohorts. Although patients with cirrhosis had a slower initial virological response as measured by the proportion of patients with HCV RNA below the lower limit of quantification at Week 1, responses converged thereafter. Positive and negative predictive values calculated for on-treatment responses were generally comparable with the overall SVR12 rate and were therefore limited indicators of outcome. SVR12 rates were not impacted by time to first undetectable HCV RNA.

CONCLUSIONS:

On-treatment responses are not useful predictors of ultimate virological response to the daclatasvir + sofosbuvir regimen.

• Authors: Kris V Kowdley, David R Nelson, Jacob P Lalezari, Terry Box, Norman Gitlin, Gary Poleynard, Mordechai Rabinovitz, Natarajan Ravendhran, Aasim M Sheikh, Asma Siddique, Rafia Bhore, Stephanie Noviello, Khurram Rana
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 36 Issue 11 Pg. 1611-1618 (11 2016) ISSN: 1478-3231 [Electronic] United States
• PMID: 27188960 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Pyrrolidines
• RNA, Viral
• Valine
• daclatasvir
• Sofosbuvir

Topics

• Adult
• Aged
• Antiviral Agents (administration & dosage, adverse effects)
• Carbamates
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Imidazoles (administration & dosage, adverse effects)
• Liver Cirrhosis (blood, etiology)
• Male
• Middle Aged
• Pyrrolidines
• RNA, Viral (blood)
• Sofosbuvir (administration & dosage, adverse effects)
• Sustained Virologic Response
• Time Factors
• United States
• Valine (analogs & derivatives)
• Viral Load
• Young Adult