HLA-B*5701 Screening for Hypersensitivity to Abacavir

N Engl J Med. 2008 Feb 7;358(6):568-79. doi: 10.1056/NEJMoa0706135.

Abstract

Background: Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir.

Methods: This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701-positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir.

Results: The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001).

Conclusions: HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug. (ClinicalTrials.gov number, NCT00340080.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Dideoxynucleosides / adverse effects*
  • Dideoxynucleosides / therapeutic use
  • Double-Blind Method
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / genetics
  • Drug Hypersensitivity / prevention & control
  • Female
  • Genetic Markers
  • Genetic Testing*
  • Genotype
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • HIV-1
  • HLA-B Antigens / genetics*
  • Humans
  • Male
  • Middle Aged
  • Patch Tests*
  • Reverse Transcriptase Inhibitors / adverse effects*
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • Dideoxynucleosides
  • Genetic Markers
  • HLA-B Antigens
  • HLA-B*57:01 antigen
  • Reverse Transcriptase Inhibitors
  • abacavir

Associated data

  • ClinicalTrials.gov/NCT00340080