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Management of direct-acting antiviral agent failures

Maria Buti1, Mar Riveiro-Barciela2, Rafael Esteban1

  • 1Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.

Journal of Hepatology
|August 25, 2015
PubMed

Insights

Hepatitis C treatment failure, though low in studies, is higher in real-world settings due to resistance. Preventing drug-resistant variants early is key to successful hepatitis C virus eradication.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacology

Background:

  • Hepatitis C virus (HCV) treatment failure rates in clinical trials are low (1-7%) but higher in real-world practice, often due to compliance issues.
  • Treatment failures typically manifest as relapse rather than on-treatment viral breakthrough.
  • HCV drug-resistant variants are frequently detected in patients who do not achieve viral eradication.

Purpose of the Study:

  • To analyze the factors influencing the development and persistence of hepatitis C drug-resistant variants.
  • To evaluate the effectiveness of current and potential treatment strategies for managing HCV treatment failures.
  • To identify optimal approaches for patients with resistance to direct-acting antiviral agents.

Main Methods:

  • Review of existing literature on HCV treatment outcomes, resistance profiles, and patient characteristics.
  • Analysis of factors contributing to treatment failure, including host, viral, and drug-related elements.
  • Evaluation of the impact of different antiviral regimens and resistance-associated variants on treatment success.

Main Results:

  • The emergence of drug-resistant variants is influenced by host factors, viral properties, drug choice, and treatment strategy.
  • NS3-4A variants often resolve post-therapy, while NS5A variants can persist for over two years.
  • Combination therapies including sofosbuvir and NS5 inhibitors are effective for patients failing first-generation protease inhibitors.

Conclusions:

  • Preventing the emergence of resistant variants through potent antivirals with high genetic barriers during initial treatment is crucial for HCV eradication.
  • Optimal treatment strategies for patients failing NS5A inhibitors or those with multidrug-resistant variants require further research.
  • Continued research is essential to define effective salvage regimens for complex HCV treatment failure cases.
Keywords:
DaclatasvirDirect-acting antiviralsHepatitis C virusInterferonLedipasvirResistance-associated variantsSimeprevirSofosbuvirTreatment

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