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Resistance testing for the treatment of chronic hepatitis C with direct acting antivirals: when and for how long?

Ana Belén Pérez1, Natalia Chueca1, Federico García1

  • 1PhD, Clinical Microbiology Department; Infectious Diseases & Clinical Microbiology Unit. Hospital Universitario San Cecilio, Instituto de Investigaciόn Ibs.Granada, Av. de la Innovaciόn S/N, 18016, Granada, Spain.

Germs
|March 24, 2017
PubMed

Insights

Resistance associated substitutions (RAS) testing in NS5A may help optimize treatment duration and drug choices for genotypes 1a and 3. However, new pangenotypic drugs may reduce the need for RAS testing in the future.

Area of Science:

  • Hepatology
  • Virology
  • Pharmacogenomics

Background:

  • The clinical utility of resistance associated substitutions (RAS) testing in Hepatitis C Virus (HCV) treatment is under ongoing debate.
  • Baseline RAS testing, particularly for NS5A in genotypes 1a and 3, has been considered to guide therapy and prevent overtreatment.
  • The emergence of new pangenotypic antiviral combinations with high genetic barriers to resistance may alter the role of RAS testing.

Purpose of the Study:

  • To evaluate the current and future role of resistance associated substitutions (RAS) testing in Hepatitis C Virus (HCV) management.
  • To assess the impact of RAS testing on treatment decisions, including drug selection and duration.
  • To consider how evolving treatment landscapes, including new pangenotypic regimens, influence the necessity of RAS testing.

Main Methods:

  • Review of current clinical guidelines and recent literature on HCV RAS testing.
  • Analysis of treatment outcomes in relation to baseline RAS status for specific HCV genotypes.
  • Prospective evaluation of the impact of novel pangenotypic antiviral agents on RAS testing strategies.

Main Results:

  • Baseline NS5A RAS testing can inform decisions regarding ribavirin use and treatment duration for HCV genotypes 1a and 3 in the absence of pangenotypic regimens.
  • RAS testing is valuable for guiding retreatment regimens, especially after failure of NS5A inhibitor-containing therapies.
  • Emerging pangenotypic drugs with high genetic barriers may diminish the routine need for baseline RAS testing.

Conclusions:

  • Resistance associated substitutions (RAS) testing remains a valuable tool for optimizing current Hepatitis C Virus (HCV) treatment regimens, particularly for specific genotypes and treatment failures.
  • The evolving landscape of highly effective, pangenotypic direct-acting antivirals may reduce the future reliance on baseline RAS testing.
  • Clinical decisions regarding RAS testing should adapt to the availability of new therapeutic options and their resistance profiles.
Keywords:
DAAHCVRASbaselinefailurenew drugs

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