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


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.
Hammond
Emma
E
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Western Australia, Australia. E.Hammond@murdoch.edu.au
Almeida
Coral-Ann
CA
Mamotte
Cyril
C
Nolan
David
D
Phillips
Elizabeth
E
Schollaardt
Tineke Asma
TA
Gill
M John
MJ
Angel
Jonathan B
JB
Neurath
Doris
D
Li
Jianping
J
Giulivi
Tony
T
McIntyre
Cathy
C
Koultchitski
Galina
G
Wong
Betty
B
Reis
Marciano
M
Rachlis
Anita
A
Cole
David E
DE
Chew
Choo Beng
CB
Neifer
Stefan
S
Lalonde
Richard
R
Roger
Michel
M
Jeanneau
Annie
A
Mallal
Simon
S
D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D017931:DNA Primers; D015343:DNA Probes, HLA; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000235:genetics; D005820:Genetic Testing / Q000592:standards*; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D016133:Polymerase Chain Reaction; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000099227:Abacavir
D019380:Anti-HIV Agents; D017931:DNA Primers; D015343:DNA Probes, HLA; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C484830:HLA-B*57:01 antigen