title: High sensitivity of human leukocyte antigen-b*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients.
abstract: BACKGROUND
  Although the human leukocyte antigen (HLA)-B*5701 is highly associated with a hypersensitivity reaction (HSR) to abacavir (ABC), variable sensitivities have been reported when clinical data alone have been used to define an ABC HSR. This study evaluated the sensitivity of detection of the HLA-B*5701 allele as a marker of ABC HSRs in both white and black patients, using skin patch testing to supplement clinical diagnosis.
  
  
  METHODS
  White and black patients, identified through chart review, were classified as having received a diagnosis of an ABC HSR based on clinical findings only (a clinically suspected ABC HSR) or based on clinical findings and a positive skin patch test result (an immunologically confirmed [IC] ABC HSR). Control subjects were racially matched subjects who tolerated ABC for >/=12 weeks without experiencing an ABC HSR. Patients and control subjects were tested for the presence of HLA-B*5701. Sensitivity, specificity, and odds ratios for the detection of HLA-B*5701 as a marker for an ABC HSR were calculated for white and black participants.
  
  
  RESULTS
  Forty-two (32.3%) of 130 white patients and 5 (7.2%) of 69 black patients who met the criteria for clinically suspected HSRs had IC HSRs. All 42 white patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 1945; 95% confidence interval, 110-34,352). Among all white patients with clinically suspected HSRs, sensitivity was 44% (57 of 130 patients tested positive for HLA-B*5701); specificity among white control subjects was 96%. Five of 5 black patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 900; 95% confidence interval, 38-21,045). Among black patients with clinically suspected HSRs, the sensitivity was 14% (10 of 69 tested positive for HLA-B*5701); specificity among black control subjects was 99%.
  
  
  CONCLUSIONS
  Although IC ABC HSRs are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for IC ABC HSRs in both US white and black patients suggests similar implications of the association between HLA-B*5701 positivity and risk of ABC HSRs in both races.
authors.affiliation: Center for AIDS Research, University of Alabama at Birmingham, Birmingham, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Saag
authors.forename: Rukmini
authors.initials: R
authors.lastname: Balu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
authors.forename: Philip
authors.initials: P
authors.lastname: Brachman
authors.forename: Claudia
authors.initials: C
authors.lastname: Martorell
authors.forename: William
authors.initials: W
authors.lastname: Burman
authors.forename: Britt
authors.initials: B
authors.lastname: Stancil
authors.forename: Michael
authors.initials: M
authors.lastname: Mosteller
authors.forename: Cindy
authors.initials: C
authors.lastname: Brothers
authors.forename: Paul
authors.initials: P
authors.lastname: Wannamaker
authors.forename: Arlene
authors.initials: A
authors.lastname: Hughes
authors.forename: Denise
authors.initials: D
authors.lastname: Sutherland-Phillips
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Mark
authors.initials: M
authors.lastname: Shaefer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects*; D044383:Black People; D015224:Dideoxynucleosides / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D012680:Sensitivity and Specificity; D012882:Skin Tests; D014481:United States; D044465:White People; D001741:Black or African American; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C484830:HLA-B*57:01 antigen