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Abacavir hypersensitivity screening

Summary

Abacavir hypersensitivity screening can help to identify people who are at high risk for a serious adverse reaction to the anti-HIV drug abacavir (Ziagen, ABC) or any drug containing abacavir. This test is meant to be used in people living with HIV who have never been exposed to abacavir. If the test is positive, you should not use abacavir or any drug containing abacavir. If the test is negative, there is a relatively low risk that you will have a reaction to abacavir, although a reaction is still possible. If you take abacavir or any drug containing abacavir, it is important for you to know how to recognize the symptoms of a hypersensitivity reaction.

What is abacavir?

Abacavir (Ziagen, ABC) is a nucleoside analogue commonly used as part of combination therapy for HIV. Abacavir is also found in the following medicines:

  • Kivexa—which contains two anti-HIV drugs in one tablet: abacavir and 3TC (lamivudine)
  • Trizivir—which contains three anti-HIV drugs in one tablet: abacavir, 3TC and AZT (Retrovir, zidovudine)
  • Triumeq—which contains three anti-HIV drugs in one tablet: abacavir, 3TC and dolutegravir (Tivicay)

Symptoms of abacavir hypersensitivity

In up to 8% of people with HIV who use abacavir, an exaggerated reaction against abacavir by the immune system—abacavir hypersensitivity—can occur. This reaction is very serious and can be fatal.

Although the hypersensitivity reaction can occur at any time while a person is taking abacavir, on average it occurs within the first six weeks of use. The manufacturer, ViiV Healthcare, states that you should stop using abacavir if you have signs or symptoms from two or more of the following groups:

  1. Fever
  2. Rash
  3. Gastrointestinal symptoms (including nausea, vomiting, diarrhea or belly pain)
  4. General symptoms (including fatigue, lack of energy, achiness)
  5. Respiratory symptoms (sore throat, shortness of breath, cough, unusual findings on X-rays of the chest)

If you develop symptoms from two or more of these groups while you are taking abacavir or any drug containing abacavir, you should stop taking this medicine and contact your doctor right away. If a hypersensitivity reaction to abacavir has indeed occurred, then abacavir should never be restarted, as a fatal reaction could occur within hours. You should also never take any other drug that contains abacavir.

What is abacavir hypersensitivity screening?

Abacavir has been available since the late 1990s. Several years ago, a screening tool for abacavir hypersensitivity became available in most HIV clinics in Canada. 

The likelihood of developing hypersensitivity to abacavir can now be assessed with a simple blood test. This test is meant to be used in people living with HIV who have never previously been exposed to abacavir. The test should not be used in people with HIV who have received a diagnosis of abacavir hypersensitivity reaction in the past.

A small sample of blood is drawn and sent to a lab. The test checks for the presence of specific genetic material, called HLA-B*5701, which has been associated with the abacavir hypersensitivity reaction.

What the test results mean

The results of the blood test are sent to the physician's office after two or three weeks. The results can be negative or positive:

  • Negative—This does not mean that you will never get a hypersensitivity reaction. But it does mean that you are at a relatively low risk (less than 1%) of developing an abacavir hypersensitivity reaction should your doctor prescribe abacavir.
  • Positive—There is a high risk of having a hypersensitivity reaction to abacavir and you should not use this drug or any other drug that contains abacavir.

The availability of this test should greatly reduce the concerns of both doctors and their patients when the use of abacavir is being discussed. However, education about the symptoms of the hypersensitivity reaction remains important in the unlikely case that there is a reaction.

Genes and abacavir hypersensitivity screening

When abacavir hypersensitivity testing was introduced, researchers in Australia who pioneered this screening used HIV-positive people whose ancestors were mainly from northwest Europe and found that HLA-B*5701 (genetic material) was relatively common. However, studies done in the United States, Quebec, Asia and elsewhere have found that abacavir hypersensitivity screening is very useful and works in people from various ethno-racial backgrounds.

Access to abacavir hypersensitivity screening in Canada

Before using abacavir, it is a very good idea to get screened for abacavir hypersensitivity. Speak to your doctor or nurse about ordering this test.

Acknowledgements

CATIE would like to thank the following researchers for their time and effort in helping us to produce this fact sheet:

  • Richard Harrigan, PhD, University of British Columbia
  • John Gill, MD, Southern Alberta Clinic, Calgary
  • Jonathan Angel, MD, Ottawa Hospital
  • Anita Rachlis, MD, University of Toronto
  • Richard Lalonde, MD, Montreal Chest Institute
  • Annalise Martin, PhD, Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital, Perth, Australia
  • Elizabeth Phillips, MD, Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital, Perth, Australia

References

  1. ViiV Healthcare ULC. Ziagen: abacavir sulfate tablets. Product Monograph. 20 January, 2021.
  2. Mallal S, Nolan D, Witt C et al. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1-reverse-transcriptase inhibitor abacavir. Lancet. 2002 Mar 2;359(9308):727-32.
  3. Ostrov DA, Grant BJ, Pompeu YA et al. Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proceedings of the National Academy of Sciences USA. 2012 Jun 19;109(25):9959-64.
  4. Lalonde RG, Thomas R, Rachlis A et al. Successful implementation of a national HLA-B*5701 genetic testing service in Canada. Tissue Antigens. 2010 Jan;75(1):12-8.
  5. Puthanakit T, Bunupuradah T, Kosalaraksa P et al. Prevalence of HLA-B*5701 among HIV-infected children in Thailand and Cambodia: implications for abacavir use. Pediatric Infectious Disease Journal. 2012 Sept 17.
  6. Berka N, Gill JM, Liacini A et al. Human leukocyte antigen (HLA) and pharmacogenetics: screening for HLA-B*57:01 among human immunodeficiency virus-positive patients from southern Alberta. Human Immunology. 2012 Feb;73(2):164-7.
  7. Pavlos R, Mallal S, Phillips E. HLA and pharmacogenetics of drug hypersensitivity. Pharmacogenomics. 2012 Aug;13(11):1285-306.
  8. Illing PT, Vivian JP, Dudek NL et al. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature. 2012 Jun 28;486(7404):554-8.
  9. Martin MA, Klein TE, Dong BJ et al. Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing. Clinical Pharmacology and Therapeutics. 2012 Apr;91(4):734-8.
  10. Phillips EJ, Chung WH, Mockenhaupt M et al. Drug hypersensitivity: pharmacogenetics and clinical syndromes. Journal of Allergy and Clinical Immunology. 2011 Mar;127(3 Suppl):S60-6.
  11. Saag M, Balu R, Phillips E et al. High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients. Clinical Infectious Diseases. 2008 Apr 1;46(7):1111-8.
  12. Mallal S, Phillips E, Carosi G et al. HLA-B*5701 screening for hypersensitivity to abacavir. New England Journal of Medicine. 2008 Feb 7;358(6):568-79.
  13. Hammond E, Almeida CA, Mamotte C et al. External quality assessment of HLA-B*5701 reporting: an international multicentre survey. Antiviral Therapy. 2007;12(7):1027-32.
  14. Martin AM, Nolan D, Gaudieri S et al. Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant. Proceedings of the National Academy of Sciences USA. 2004 Mar 23;101(12):4180-5.
  15. Rauch A, Nolan D, Martin A et al. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clinical Infectious Diseases. 2006 Jul 1;43(1):99-102.

Author(s): Hosein SR

Published: 2021