title: HLA-B*5701 screening for hypersensitivity to abacavir.
abstract: BACKGROUND
  Hypersensitivity reaction to abacavir is strongly associated with the presence of the HLA-B*5701 allele. This study was designed to establish the effectiveness of prospective HLA-B*5701 screening to prevent the hypersensitivity reaction to abacavir.
  
  
  METHODS
  This double-blind, prospective, randomized study involved 1956 patients from 19 countries, who were infected with human immunodeficiency virus type 1 and who had not previously received abacavir. We randomly assigned patients to undergo prospective HLA-B*5701 screening, with exclusion of HLA-B*5701-positive patients from abacavir treatment (prospective-screening group), or to undergo a standard-of-care approach of abacavir use without prospective HLA-B*5701 screening (control group). All patients who started abacavir were observed for 6 weeks. To immunologically confirm, and enhance the specificity of, the clinical diagnosis of hypersensitivity reaction to abacavir, we performed epicutaneous patch testing with the use of abacavir.
  
  
  RESULTS
  The prevalence of HLA-B*5701 was 5.6% (109 of 1956 patients). Of the patients receiving abacavir, 72% were men, 84% were white, and 18% had not previously received antiretroviral therapy. Screening eliminated immunologically confirmed hypersensitivity reaction (0% in the prospective-screening group vs. 2.7% in the control group, P<0.001), with a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reaction was clinically diagnosed in 93 patients, with a significantly lower incidence in the prospective-screening group (3.4%) than in the control group (7.8%) (P<0.001).
  
  
  CONCLUSIONS
  HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir. In predominantly white populations, similar to the one in this study, 94% of patients do not carry the HLA-B*5701 allele and are at low risk for hypersensitivity reaction to abacavir. Our results show that a pharmacogenetic test can be used to prevent a specific toxic effect of a drug. (ClinicalTrials.gov number, NCT00340080.)
authors.affiliation: Royal Perth Hospital and Murdoch University, Perth, Australia. s.mallal@murdoch.edu.au
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
authors.forename: Giampiero
authors.initials: G
authors.lastname: Carosi
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Cassy
authors.initials: C
authors.lastname: Workman
authors.forename: Janez
authors.initials: J
authors.lastname: Tomazic
authors.forename: Eva
authors.initials: E
authors.lastname: Jägel-Guedes
authors.forename: Sorin
authors.initials: S
authors.lastname: Rugina
authors.forename: Oleg
authors.initials: O
authors.lastname: Kozyrev
authors.forename: Juan Flores
authors.initials: JF
authors.lastname: Cid
authors.forename: Phillip
authors.initials: P
authors.lastname: Hay
authors.forename: David
authors.initials: D
authors.lastname: Nolan
authors.forename: Sara
authors.initials: S
authors.lastname: Hughes
authors.forename: Arlene
authors.initials: A
authors.lastname: Hughes
authors.forename: Susanna
authors.initials: S
authors.lastname: Ryan
authors.forename: Nicholas
authors.initials: N
authors.lastname: Fitch
authors.forename: Daren
authors.initials: D
authors.lastname: Thorborn
authors.forename: Alastair
authors.initials: A
authors.lastname: Benbow
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology; D015497:HIV-1; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010328:Patch Tests; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000099227:Abacavir
chemical_list: D015224:Dideoxynucleosides; D005819:Genetic Markers; D015235:HLA-B Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C484830:HLA-B*57:01 antigen