Related Experiment Video

Updated: Jun 3, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
05:46

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors

Published on: April 9, 2014

Treatment failure and resistance with direct-acting antiviral drugs against hepatitis C virus

Jean-Michel Pawlotsky1

  • 1Department of Virology, Hôpital Henri Mondor, Université Paris-Est Créteil, France. michel.pawlotsky@hmn.aphp.fr

Hepatology (Baltimore, Md.)
|March 5, 2011
PubMed

Insights

New hepatitis C virus (HCV) treatments combining direct-acting antivirals (DAAs) face resistance concerns. Understanding resistance patterns is key to optimizing future DAA therapies for HCV infection.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacology

Background:

  • Current chronic hepatitis C virus (HCV) treatment relies on pegylated interferon-alfa and ribavirin.
  • Direct-acting antiviral (DAA) development shows potential for HCV treatment.
  • In vitro and in vivo studies indicate that DAAs alone may select for resistant HCV strains.

Purpose of the Study:

  • To review resistance patterns of developing HCV DAA drugs.
  • To examine mechanisms of treatment failure with DAA and interferon-alfa/ribavirin combinations.
  • To discuss consequences of treatment failure and optimize future DAA therapies.

Main Methods:

  • Review of in vitro and in vivo studies on DAA resistance.
  • Analysis of treatment failure mechanisms in patients receiving DAA combinations.
  • Examination of genetic barriers to resistance for first-generation protease inhibitors.

Main Results:

  • Treatment failures in triple therapy (pegylated interferon-alfa, ribavirin, protease inhibitor) are often linked to inadequate response to interferon-alfa and ribavirin.
  • First-generation protease inhibitors exhibit a low genetic barrier to resistance.
  • DAA resistance is a significant concern that may undermine therapy efficacy.

Conclusions:

  • Resistance to DAAs can compromise HCV treatment outcomes.
  • Understanding resistance mechanisms is crucial for developing effective DAA-based therapies.
  • Optimizing future DAA therapies requires careful consideration of resistance patterns and combination strategies.

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

An Affordable HIV-1 Drug Resistance Monitoring Method for Resource Limited Settings19:57

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

Published on: March 30, 2014

Related Concept Videos

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 retrovirus to...
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. The...
Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
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 binding...
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...
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment01:08

Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

Hepatic impairment, characterized by decreased liver function, does not uniformly mandate adjustments in drug dosage. Whether dosage modifications are necessary depends on various factors related to the drug's metabolism and elimination pathways. If a drug is primarily excreted via the kidneys and bypasses significant hepatic processing, if it undergoes minimal metabolic transformation in the liver, or if it is volatile and primarily expelled through the lungs, dose adjustments may not be...