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Hepatitis C Viral RNA Genotype 1 NS5A Drug-resistance

Test codes: 92447, 93871, 93873

NS5A inhibitors are antiviral drugs. They are classified as direct acting agents (DAAs) and work by inhibiting the HCV NS5A protein.1,2

Recommended NS5a inhibitors for treatment-naïve HCV genotype 1 include Mavyret® (glecaprevir/pibrentasvir), Harvoni® (ledipasvir/sofosbuvir), Epclusa® (sofosvubir/velpatasvir) and Zepatier® (elbasvir/grazoprevir).  The triple-drug combination Vosevi® (sofosvubir/velpatasvir/voxilaprevir) is recommended for treatment-experienced patients.3-7

Quest Diagnostics uses reverse transcription polymerase chain reaction (PCR) and DNA sequencing of genotype 1 NS5A codons 1 to 150. This method detects NS5A inhibitor resistance-associated variants (RAVs), including those identified at positions 28, 30, 31, 58, and 93 on the NS5A gene. The RAVs include Y93H, which is associated with reduced susceptibility to all FDA-approved NS5A inhibitors.8

Yes, in certain circumstances. The American Association for the Study of Liver Disease (AASLD) and the Infectious Disease Society of America (IDSA) guidelines recommend NS5A resistance testing in treatment-naive genotype 1a patients being considered for elbasvir/grazoprevir treatment; such testing should also be considered before initiating sofosbuvir/ledipasvir treatment.7

Yes, please refer to the Hepatitis C Viral RNA Genotype 3 NS5A Drug-resistance test (test code 93325, HCV RNA genotype 1 NS5A drug-resistance FAQ).

Example 1

HCV NS5A Subtype:                 1a

Daclatasvir Resistance:            PROBABLE

Ledipasvir Resistance:             PROBABLE

Ombitasvir Resistance:            PROBABLE

Elbasvir Resistance:                 PROBABLE

Velpatasvir Resistance:            PROBABLE

MUTATIONS DETECTED         Y93H

Example 2

HCV NS5A Subtype:                 1a

Daclatasvir Resistance:            PROBABLE

Ledipasvir Resistance:             PROBABLE

Ombitasvir Resistance:            NOT PREDICTED

Elbasvir Resistance:                 PROBABLE

Velpatasvir Resistance:            NOT PREDICTED

MUTATIONS DETECTED         L31M

Example 3

HCV NS5A Subtype:                 1b

Daclatasvir Resistance:            NOT PREDICTED

Ledipasvir Resistance:             NOT PREDICTED

Ombitasvir Resistance:            NOT PREDICTED

Elbasvir Resistance:                 NOT PREDICTED

Velpatasvir Resistance:            NOT PREDICTED

MUTATIONS DETECTED         NONE

Quest Diagnostics offers the following NS5A drug testing options:

  • Hepatitis C Viral RNA Genotype 1 NS5A Drug-resistance (test code 92447)
  • Hepatitis C Viral RNA Genotype, with Reflex to HCV NS5A Drug-resistance (test code 93871); if the HCV genotype is 1a, NS5A drug-resistance test will be performed at additional charge.
  • Hepatitis C Viral RNA, Quantitative Real-Time PCR with Reflexes (test code 93873); if the HCV RNA is ≥2,000 IU/mL, the genotype test will be performed at additional charge; if the HCV genotype is 1a, the NS5A drug-resistance test will be performed at additional charge.

References

  1. Rupp D, Bartenschlager R. Targets for antiviral therapy of hepatitis C. Semin Liver Dis. 2014;34:9-21. doi:10.2147/IDR.S36247.
  2. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56. doi:10.2147/IDR.S36247.
  3. MAVYRET™[package insert]. Abbvie; Chicago, IL; 8/2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209394s000lbl.pdf
  4. HARVONI® [package insert]. Foster City, CA: Gilead; 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf
  5. EPCLUSA® [package insert]. Gilead; Foster City, CA; 6/2016. http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208341s000lbl.pdf
  6. Zepatier® [package insert]. Merck Sharpe & Dohme Corp.; 2016. http://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf
  7. AASLD-IDSA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/. Accessed December 27, 2024.
  8. Lontok, E, Harrington, P, Howe, A, et al. Hepatitis C virus drug-resistance-associated substitutions: State of the art summary. Hepatology. 2015;62:1623-1632. doi:10.1002/hep.27934.

 

This FAQ is provided for informational purposes only and is not intended as medical advice. A physician’s test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

 

Document FAQS.173 Version: 4

Version 4 effective 05/19/2025 to present

Version 3 effective 08/22/2016 to 05/19/2025 
Version 2 effective 03/26/2016 to 08/22/2016
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