0-9
A B C D E F G H I J K L M N O
P Q R S T U V W X Y Z
  • No FAQs found
  • No FAQs found
  • No FAQs found
  • No FAQs found
  • No FAQs found
  • No FAQs found
  • No FAQs found

Hepatitis C Viral RNA Genotype 1 NS5A Drug Resistance

Test code(s) 92447

This is an outdated version of this FAQ. It was effective 02/12/2016 to 02/28/2016.

The current version is available here.

Question 1. What are hepatitis C virus (HCV) NS5A inhibitors?

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

Question 2. Which NS5A inhibitors are approved for clinical use?

Ledipasvir was approved by the FDA in October 2014 as a component of HARVONI®(sofosbuvir and ledipasvir).3 Ombitasvir was approved as a component of VIEKIRA PAK® (ombitasvir, paritaprevir, ritonavir and dasabuvir) in December 2014.4 Daklinza® (daclatasvir) was approved by the FDA in July 2014.5 Additional NS5A inhibitors are currently under FDA review or are undergoing clinical trials.

Question 3. Which method is available to test for HCV NS5A inhibitor resistance?

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 approved NS5A inhibitors.6

Question 4. Is HCV genotype 1 NS5A drug resistance testing recommended before prescribing an NS5A inhibitor-containing regimen to patients requiring retreatment?

Yes, in certain circumstances. The AASLD and IDSA guidelines recommend "For patients with cirrhosis or other patients who require retreatment urgently, testing for resistance-associated variants that confer decreased susceptibility to NS3 protease inhibitors and to NS5A inhibitors is recommended. The specific drugs used in the retreatment regimen should be tailored to the results of this testing as described below."7 Additionally, the guidelines suggest consultation with an expert in the treatment of HCV infection if uncertainty remains regarding the applicability of NS5A RAV testing.7

Question 5. Is HCV genotype 1 NS5A drug resistance testing recommended before prescribing an NS5A inhibitor-containing regimen to treatment-naïve patients?

The AASLD and IDSA guidelines do not currently recommend routine use of NS5A resistance testing in this circumstance.7 Naturally occuring NS5A RAVs conferring moderate to high levels of resistance have been found at a low prevalence in HCV genotype 1a and 1b patients.8,9 However, the impact of these baseline variants on treatment efficacy with combination DAA regimens may be limited and further studies are warranted.3,4,10

The guidelines suggest consultation with an expert in the treatment of HCV infection if uncertainty remains regarding the applicability of NS5A RAV testing.7

Question 6. How are HCV genotype 1 NS5A drug resistance test results reported?

 

Example 1  
HCV NS5A Subtype:   1a
Daclatasvir Resistance:   PREDICTED
Ledipasvir Resistance:   PREDICTED
Ombitasvir Resistance: PREDICTED
MUTATIONS DETECTED Y93H
   
Example 2  
HCV NS5A Subtype:   1a
Daclatasvir Resistance:   PREDICTED
Ledipasvir Resistance:   PREDICTED
Ombitasvir Resistance: NOT PREDICTED
MUTATIONS DETECTED L31M
   
Example 3  
HCV NS5A Subtype:   1b
Daclatasvir Resistance:   NOT PREDICTED
Ledipasvir Resistance:   NOT PREDICTED
Ombitasvir Resistance: NOT PREDICTED
MUTATIONS DETECTED NONE

 

References

  1. Rupp D, Bartenschlager R. Targets for antiviral therapy of hepatitis C. Semin Liver Dis. 2014;34:9-21.
  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.
  3. HARVONI® [package insert]. Foster City, CA: Gilead; 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205834s000lbl.pdf
  4. VIEKIRA PAK® [package insert]. Chicago, IL: Abbvie Incorporated; 2014. http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206619lbl.pdf.
  5. Daklinza® [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206843Orig1s000lbl.pdf.
  6. 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.
  7. American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/. Accessed December 16, 2015.
  8. McCormick AL, Wang L, Garcia-Diaz A, et al. Prevalence of baseline polymorphisms for potential resistance to NS5A inhibitors in drug-naive individuals infected with hepatitis C genotypes 1-4. Antiviral Ther. 2014;20:81-85.
  9. Dietz J, Susser S, Berkowski C, et al. Consideration of viral resistance for optimization of direct antiviral therapy of hepatitis C virus genotype 1-infected patients. PLoS One. 2015;10:e0134395.
  10. Cento V, Chevaliez S, Federico Perno C. Resistance to direct-acting antiviral agents: clinical utility and significance. Curr Opin HIV AIDS. 2015;10:381-389.
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 his/her education, clinical expertise, and assessment of the patient.
Document FAQS.173 Version: 0
 
Effective 02/12/2016 to present