title: 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.
authors.affiliation: Alberta Health Services, Calgary Laboratory Services, 9, Calgary, Alberta T2L 2K8, Canada. Noureddine.Berka@cls.ab.ca
authors.forename: Noureddine
authors.initials: N
authors.lastname: Berka
authors.forename: John M
authors.initials: JM
authors.lastname: Gill
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Liacini
authors.forename: Tyler
authors.initials: T
authors.lastname: O'Bryan
authors.forename: Faisal M
authors.initials: FM
authors.lastname: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000416:Alberta; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000150:complications* / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D012189:Retrospective Studies; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C103707:HLA-B57 antigen