External quality assessment of HLA-B*5701 reporting: an international multicentre survey

Antivir Ther. 2007;12(7):1027-32.

Abstract

Objectives: HLA-B*5701 strongly predicts abacavir hypersensitivity (HSR), but implementation of effective routine screening into clinical practice requires testing be practical and accurate. We tested the proficiency of HLA-B*5701 typing among laboratories using sequence-specific primer PCR.

Design and methods: DNA panels (1 and 2) were distributed to seven laboratories (A to G) for blinded typing of the HLA-B*5701 allele. Panel 1 (n = 10 samples; n = 7 laboratories) included 3 positives and other closely related B17 subtypes (B*5702, B*5703, B*5704 and B*5801). Panel 2 (n = 96 samples; n = 4 laboratories) included 36 positives among a broad spectrum of other B alleles. Two laboratories (A and B) also submitted 96 routine samples, typed by the same methodology, to the reference centre for additional analysis by sequence-based typing.

Results: All laboratories correctly typed panel 1 for HLA-B*5701 carriage. Laboratories A, B and C identified HLA-B*5701 alleles in panel 2 with 100% sensitivity and 100% specificity. Laboratory D reported one false negative, reportedly due to a sampling error. The results obtained for routine samples typed by laboratories A and B and those generated by the reference laboratory using sequencing were fully concordant.

Conclusions: Detection of HLA-B*5701 alleles among laboratories was 100% specific and 99.4% sensitive, indicating that participating HIV testing laboratories were currently offering effective primary screening to identify individuals at high risk of abacavir HSR. Accurate reporting of HLA-B*5701 status is critical for the safe administration of this drug and participation in quality assurance programmes by all sites who report HLA-B*5701 status should be promoted.

Publication types

  • Evaluation Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Anti-HIV Agents / adverse effects
  • Anti-HIV Agents / therapeutic use
  • DNA Primers
  • DNA Probes, HLA
  • Dideoxynucleosides / adverse effects*
  • Dideoxynucleosides / therapeutic use
  • Drug Hypersensitivity / genetics
  • Genetic Testing / standards*
  • HLA-B Antigens / genetics*
  • Humans
  • Polymerase Chain Reaction
  • Quality Control
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Anti-HIV Agents
  • DNA Primers
  • DNA Probes, HLA
  • Dideoxynucleosides
  • HLA-B Antigens
  • HLA-B*57:01 antigen
  • abacavir