Human leukocyte antigen (HLA) and pharmacogenetics: screening for HLA-B*57:01 among human immunodeficiency virus-positive patients from southern Alberta

Abstract

The field of pharmacogenetics is witnessing a growing interest in the role of the human leukocyte antigen (HLA) in manifestation of adverse drug reactions (ADR). Here we report a retrospective analysis of the association of HLA-B*5701 with abacavir hypersensitivity syndrome (AHS) in a large Canadian cohort of 489 human immunodeficiency virus-1-positive patients exposed to abacavir. A total of 3.7% of abacavir-exposed patients had developed AHS. Using polymerase chain reaction sequence-specific primer-based genotyping, the HLA-B*5701 allele was observed in 20 patients (4.1%). Of the 20 HLA-B*5701(+) abacavir-treated patients, 18 (90%) had developed AHS. Carriage of the HLA-B*5701 allele indicated a strong association with abacavir hypersensitivity (p < 0.0001; odds ratio = 6,934; 95% confidence interval = 321-149,735). HLA-B*5701 genotyping demonstrated high sensitivity, specificity, and positive and negative predictive values. The data derived from the study highlight the importance of engaging histocompatibility and immunogenetics laboratories in taking a lead in mapping other less characterized HLA and immunogenetic markers associated with ADRs.