Resistance to DAAs: When to Look and When It Matters

• Published in: Current HIV/AIDS reports 2017-12, Vol.14 (6), p.229-237
• Main Author: Wyles, David L.
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution; Antiviral Agents - therapeutic use; Cirrhosis; Co-infections and Comorbidity (S Naggie; Drug Resistance, Viral; Hepacivirus - drug effects; Hepacivirus - genetics; Hepatitis C, Chronic - diagnosis; Hepatitis C, Chronic - drug therapy; Humans; Liver cirrhosis; Medicine; Medicine & Public Health; Section Editor; Topical Collection on Co-infections and Comorbidity; Viral Nonstructural Proteins - antagonists & inhibitors; Viral Nonstructural Proteins - genetics
• ISSN: 1548-3568; 1548-3576
• 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. Summary 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.