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Quest Diagnostics

HIV-1 Integrase Genotype

Test codes: 16868, 90926, 91691, 91692

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 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

As of September 2023, 5 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), Gilead Sciences10
  • Cabotegravir, available as a component of CABENUVA® (cabotegravir and rilpivirine extended-release injectable suspensions), ViiV Healthcare11

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

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.6-15 In addition, the R263K mutation may cause reduced susceptibility to dolutegravir, bictegravir, and cabotegravir.15-17

Integrase genotyping should be performed in people failing INSTI-based regimens to determine whether to include a drug from this class in subsequent regimens.18 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.18  Integrase genotyping is also recommended before treatment initiation for people with HIV and a history of using long-acting cabotegravir as PrEP.18

Since this test uses viral RNA extracted from the plasma of HIV-infected patients, a minimum viral load of 500 to 1000 copies/mL is recommended.

The INSTI-related mutation(s) detected and the associated prediction for resistance to raltegravir, elvitegravir, and dolutegravir are reported as shown in the following examples:

Example 1

 

Raltegravir Resistance:  

PREDICTED

Elvitegravir Resistance:  

PREDICTED

Dolutegravir Resistance:   

NOT PREDICTED

Bictegravir Resistance:  

NOT PREDICTED

Cabotegravir 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

Cabotegravir Resistance:

NOT PREDICTED

Mutations Detected:

NONE

Example 3

 

Raltegravir Resistance:   

NOT PREDICTED

Elvitegravir Resistance:    

 NOT PREDICTED

Dolutegravir Resistance:  

PROBABLE

Bictegravir Resistance:

PROBABLE
Cabotegravir Resistance: PROBABLE

Mutations Detected:

R263K

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; 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/210251s007lbl.pdf
  11. CABENUVA. Prescribing information. ViiV Healthcare Inc; 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212888s005s006lbl.pdf
  12. 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
  13. 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
  14. Oliveira M, Ibanescu RI, Anstett K, et al. Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Retrovirology. 2018;15(1):56. doi:10.1186/s12977-018-0440-3
  15. Anstett K, Brenner B, Mesplede T, et al. HIV drug resistance against strand transfer integrase inhibitors. Retrovirology. 2017;14(1):36. doi:10.1186/s12977-017-0360-7
  16. Underwood M, Horton J, Nangle K, Hopking J, Smith K, Aboud M, Wynne B, Sievers J, Stewart EL, Wang R. Integrase Inhibitor Resistance Mechanisms and Structural Characteristics in Antiretroviral Therapy-Experienced, Integrase Inhibitor-Naive Adults with HIV-1 Infection Treated with Dolutegravir plus Two Nucleoside Reverse Transcriptase Inhibitors in the DAWNING Study. Antimicrob Agents Chemother. 2022;66(1):e0164321. doi:10.1128/AAC.01643-21. Erratum in: Antimicrob Agents Chemother. 2023;67(3):e0032622.
  17. Vavro C, Ruel T, Wiznia A, et al. Emergence of Resistance in HIV-1 Integrase with Dolutegravir Treatment in a Pediatric Population from the IMPAACT P1093 Study. Antimicrob Agents Chemother. 2022;66(1):e0164521. doi: 10.1128/AAC.01645-21
  18. 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. Published March 23, 2023. Accessed August 8, 2023. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv

 

This FAQ is provided for informational purposes only and is not intended as medical advice. 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.135 Version: 3

Version 3 effective 12/29/2023 to present

Version 2 effective 06/28/2021 to 12/29/23

Version 1 effective 02/04/2016 to 06/28/2021

Version 0 effective 02/17/2014 to 02/03/2016

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