Abacavir pharmacogenetics--from initial reports to standard of care

Pharmacotherapy. 2013 Jul;33(7):765-75. doi: 10.1002/phar.1278. Epub 2013 May 3.

Abstract

Abacavir is a nucleoside analogue reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus infection as part of a multidrug, highly active antiretroviral therapy regimen. Despite its efficacy, approximately 5% of individuals who receive abacavir develop an immune-mediated hypersensitivity reaction (HSR) that warrants immediate discontinuation of abacavir and switching to an alternative antiretroviral regimen. Abacavir HSR is associated with individuals who carry the *57:01 variant in the human leukocyte antigen B (HLA-B) gene. There is a large volume of evidence to show that those who carry HLA-B*57:01 are at significantly increased risk of developing HSR and should not receive abacavir. Pharmacogenetic screening to ensure individuals who carry HLA-B*57:01 do not receive abacavir can reduce the incidence of HSR and is now considered the standard of care before prescribing abacavir. Genetic testing to prevent abacavir HSR is currently one of the best examples of integrating pharmacogenetic testing into clinical practice.

Keywords: AIDS; HIV; HLA; abacavir; drug hypersensitivity; genetic testing; pharmacogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • Dideoxynucleosides / administration & dosage
  • Dideoxynucleosides / adverse effects
  • Dideoxynucleosides / therapeutic use*
  • Drug Hypersensitivity / etiology
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / virology
  • HLA-B Antigens / genetics
  • Humans
  • Pharmacogenetics / methods
  • Reverse Transcriptase Inhibitors / administration & dosage
  • Reverse Transcriptase Inhibitors / adverse effects
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Standard of Care

Substances

  • Anti-HIV Agents
  • Dideoxynucleosides
  • HLA-B Antigens
  • HLA-B*57:01 antigen
  • Reverse Transcriptase Inhibitors
  • abacavir