Resistance to DAAs: When to Look and When It Matters

Curr HIV/AIDS Rep. 2017 Dec;14(6):229-237. doi: 10.1007/s11904-017-0369-5.


Purpose of review: This review provides an overview of HCV resistance-associated substitutions (RASs) with a focus on NS3 protease and NS5A inhibitor resistance. Treatment approaches for managing resistance are also covered including the use of newly approved therapies with improved resistance profiles.

Recent findings: HCV RASs are frequently selected if the patient is not cured during treatment; NS5A RASs persist for prolonged periods of time (years) after treatment failure and may adversely impact retreatment responses. Newly approved regimens with improved potency and resistance profiles are less impacted by resistance and provide the best retreatment options for patients who previously failed DAA therapy. The clinical impact of HCV RASs has been lessened significantly with the introduction of new DAA treatment regimens. Routine testing for resistance is unlikely to impact retreatment approaches if newer regimens are accessible. Knowledge of factors, such as the presence of cirrhosis and prior treatment regimens, remain as the key to optimizing retreatment approaches.

Keywords: Direct acting antivirals; HCV; Resistance-associated substitutions.

Publication types

  • Review

MeSH terms

  • Amino Acid Substitution
  • Antiviral Agents / therapeutic use
  • Drug Resistance, Viral*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / diagnosis*
  • Hepatitis C, Chronic / drug therapy
  • Humans
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / genetics*


  • Antiviral Agents
  • NS-5 protein, hepatitis C virus
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins