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HIV-1 Integrase Genotype

Test code(s) 16868(X), 90926(X), 91691(X), 91692(X)

Question 1. What are HIV-1 integrase inhibitors?

Integrase inhibitors, also called integrase strand transfer inhibitors (INSTIs), are drugs that can inhibit integration of reverse-transcribed HIV-1 DNA into the infected patient’s genomic DNA.1,2 The integration is normally catalyzed by the HIV-1 integrase enzyme. Inhibition of the enzyme blocks viral replication.

Integrase inhibitors are effective when used as part of an antiretroviral therapy regimen.3-5

Question 2. Which HIV-1 integrase inhibitors are approved for clinical use?

As of February 2018, 4 integrase inhibitors, have been approved:

  • ISENTRESS® (raltegravir), Merck6
  • TIVICAY® (dolutegravir), ViiV Healthcare7
  • Elvitegravir, available as a component of STRIBILD® (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate), Gilead Sciences8; and GENVOYA® (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide), Gilead Sciences9
  • Bictegravir, available as a component of BIKTARVY® (bictegravir, emtricitabine and tenofovir alfenamide), Gilean Sciences10

Additional integrase inhibitors are currently undergoing clinical trials or are in development.

Question 3. What methods are available to test for HIV-1 integrase inhibitor resistance?

A genotypic assay that uses reverse transcription of HIV RNA, followed by PCR amplification and DNA sequencing of the integrase gene, can detect mutations associated with integrase inhibitor resistance. Such mutations include N155H, Y143C/H/R, and Q148H/K/R, which are associated with resistance to raltegravir and/or elvitegravir. Q148H/K/R, in combination with additional mutations, may also cause resistance to dolutegravir and bictegravir.6-12

Question 4. Is HIV-1 integrase genotyping required before prescribing an HIV-1 integrase inhibitor-containing antiretroviral regimen?

No. Integrase genotyping should be performed in people failing INSTI-based regimens, to determine whether to include a drug from this class in subsequent regimens.13 If transmitted INSTI resistance is a concern in a treatment-naive patient, the healthcare provider may wish to supplement standard genotypic resistance testing with an INSTI genotype test.13

Question 5. What is the minimum HIV-1 viral load required for integrase genotyping?

Since this test uses viral RNA extracted from the plasma of HIV-infected patients, a minimum viral load of 500 to1000 copies/mL is recommended.

Question 6. How are the results of the HIV-1 integrase genotype test reported?

The INSTI-related mutation(s) detected and the associated prediction for resistance to raltegravir, elvitegravir, and dolutegravir are reported.

Example 1

 

Raltegravir Resistance:  

PREDICTED

Elvitegravir Resistance:  

PREDICTED

Dolutegravir Resistance:   

NOT PREDICTED

Bictegravir Resistance:  

NOT PREDICTED

Mutations Detected:

N155H, E138A, D232N

 

 

Example 2

 

Raltegravir Resistance:  

NOT PREDICTED

Elvitegravir Resistance:  

NOT PREDICTED

Dolutegravir Resistance:  

NOT PREDICTED

Bictegravir Resistance:

NOT PREDICTED

Mutations Detected:

NONE

 

 

Example 3

 

Raltegravir Resistance:   

PREDICTED

Elvitegravir Resistance:    

PREDICTED

Dolutegravir Resistance:  

PROBABLE

Bictegravir Resistance:

PROBABLE

Mutations Detected:

Q148K, G140A/S

 

References

  1. Quashie PK, Sloan RD, Wainberg MA. Novel therapeutic strategies targeting HIV integrase. BMC Med. 2012;10:34. doi:10.1186/1741-7015-10-34
  2. Hazuda DJ. HIV integrase as a target for antiretroviral therapy. Curr Opin HIV AIDS. 2012;7(5):383-389. doi:10.1097/COH.0b013e3283567309
  3. Jegede O, Babu J, Di Santo R, et al. HIV type 1 integrase inhibitors: from basic research to clinical implications. AIDS Rev. 2008;10(3):172-189.
  4. Powderly WG. Integrase inhibitors in the treatment of HIV-1 infection. J Antimicrob Chemother. 2010;65(12):2485-2488. doi:10.1093/jac/dkq350
  5. Messiaen P, Wensing AMJ, Fun A, et al. Clinical use of HIV integrase inhibitors: a systematic review and meta-analysis. PLoS One. 2013;8(1):e52562. doi:10.1371/journal.pone.0052562
  6. Isentress® (raltegravir). Prescribing information. Merck Sharp & Dohme Corp; 2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022145s018lbl.pdf
  7. Tivicay®(dolutegravir). Prescribing information. ViiV Healthcare; 2013.  http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf
  8. Stribild®. Prescribing information. Gilead Sciences Inc; 2012.  http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203100s000lbl.pdf
  9. Genvoya®. Prescribing information. Gilead Sciences Inc; 2015. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207561s000lbl.pdf
  10. BIKTARVY®. Prescribing information. Gilead Sciences Inc; 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210251s000lbl.pdf
  11. Mesplède T, Quashie PK, Wainberg MA. Resistance to HIV integrase inhibitors. Curr Opin HIV AIDS. 2012;7(5):401-408. doi:10.1097/COH.0b013e328356db89
  12. Geretti AM, Armenia D, Ceccherini-Silberstein F. Emerging patterns and implications of HIV-1 integrase inhibitor resistance. Curr Opin Infect Dis. 2012;25(6):677-686. doi:10.1097/QCO.0b013e32835a1de7
  13. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. Department of Health and Human Services. Updated June 4, 2021. Accessed June 8, 2021. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf
This FAQ is provided for informational purposes only and is not intended as medical advice. A clinician’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.135 Version: 2
 
Version 2 effective 06/28/2021 to present
Version 1 effective 02/04/2016 to 06/28/2021
Version 0 effective 02/17/2014 to 02/03/2016