Related Experiment Video

Updated: Mar 31, 2026

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings
19:57

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings

Published on: March 30, 2014

19.5K

Development and persistence of DAA resistance associated mutations in patients failing HCV treatment

Stefania Paolucci1, Loretta Fiorina1, Bianca Mariani1

  • 1Molecular Virology Unit, Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy.

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology
|October 23, 2015
PubMed
Abstract

Insights

Hepatitis C virus (HCV) resistance-associated mutations (RAMs) frequently emerge during treatment with direct-acting antiviral agents (DAAs), impacting treatment success. Genotype 1a strains showed higher failure rates, and resistance can persist post-therapy.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacogenomics

Background:

  • Standard treatment for genotype 1 Hepatitis C Virus (HCV) involves direct-acting antiviral agents (DAAs) with pegylated-interferon (PegIFN) and ribavirin (RBV).
  • Virologic response to these therapies can be compromised by pre-existing or emerging HCV resistance-associated mutations (RAMs).

Purpose of the Study:

  • To investigate the emergence and persistence of RAMs in the NS3 and NS5B genes.
  • To analyze RAMs in DAA-naïve patients experiencing treatment failure.

Main Methods:

  • Direct sequencing of the HCV NS3 gene was performed.
  • Analysis included 49 DAA-naïve patients with HCV genotype 1 infection.

Main Results:

  • Treatment failure occurred in 34.7% of patients on PegIFN/RBV/telaprevir and 22.2% on PegIFN/RBV/boceprevir.
  • RAMs at specific amino acid positions (36, 54, 80, 155) were identified in 75% of telaprevir failures and 50% of boceprevir failures.
  • Drug-resistant variants persisted for up to 3-7 months post-therapy in 60% of patients.

Conclusions:

  • Telaprevir-based regimens showed a higher failure rate compared to boceprevir-based regimens.
  • HCV genotype 1a was significantly associated with higher treatment failure rates due to resistant strains.
  • Baseline and on-treatment resistance testing is recommended for optimizing novel HCV combination therapies.
Keywords:
Drug resistanceHCV genotype 1Hepatitis C virusProtease inhibitorsSequencing

More Related Videos

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

2.6K
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors05:46

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors

Published on: April 9, 2014

18.5K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K
Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
50.6K
Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver.
37
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

1.5K
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
40.8K
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow01:26

Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow

Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
335