Hepatitis C virus resistance to the new direct-acting antivirals.

Abstract

INTRODUCTION:

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs).

AREAS COVERED:

Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted.

EXPERT OPINION:

Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

• Authors: Isabella Esposito, Julieta Trinks, Vicente Soriano
• Journal: Expert opinion on drug metabolism & toxicology (Expert Opin Drug Metab Toxicol) Vol. 12 Issue 10 Pg. 1197-209 (Oct 2016) ISSN: 1744-7607 [Electronic] England
• PMID: 27384079 (Publication Type: Journal Article, Review)

Chemical References

• Antiviral Agents

Topics

• Antiviral Agents (pharmacology)
• Drug Resistance, Viral
• Hepacivirus (drug effects, genetics, isolation & purification)
• Hepatitis C (drug therapy, virology)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Treatment Failure
• Virus Replication