title: Novel sensitive, specific and rapid pharmacogenomic test for the prediction of abacavir hypersensitivity reaction: HLA-B*57:01 detection by real-time PCR.
abstract: OBJECTIVE
  International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B*57:01 detection has been developed in the present study.
  
  
  METHODS
  Two sets of sequence-specific primers were designed, and amplification rapidly detected by real-time PCR.
  
  
  RESULTS
  A total of 108 samples were analyzed in a single-blind fashion, and 41 samples were identified as positive. Complete agreement, with κ = 1 (standard error = 0.0962, p < 0.0001), was found, with a validated methodology used in the EPI109367 clinical trial funded by GlaxoSmithKline, and consisting of low-resolution sequence-specific oligonucleotide PCR, followed by high-resolution sequence-specific oligonucleotide PCR carried out on the HLA-B*57-positive samples.
  
  
  CONCLUSIONS
  We provided a detailed characterization of a novel HLA-B*57:01 screening test, which can be easily implemented by those laboratories already involved in the detection of viral load and virus genotyping. Original submitted 26 October 2010; Revision submitted 13 December 2010.
authors.affiliation: Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Dello Russo
authors.forename: Lucia
authors.initials: L
authors.lastname: Lisi
authors.forename: Alessia
authors.initials: A
authors.lastname: Lofaro
authors.forename: Simona
authors.initials: S
authors.lastname: Di Giambenedetto
authors.forename: Bruno
authors.initials: B
authors.lastname: Federico
authors.forename: Giordano
authors.initials: G
authors.lastname: Madeddu
authors.forename: Marianna
authors.initials: M
authors.lastname: Salerno
authors.forename: Maria Stella
authors.initials: MS
authors.lastname: Mura
authors.forename: Antonella
authors.initials: A
authors.lastname: Pirazzoli
authors.forename: Andrea
authors.initials: A
authors.lastname: de Luca
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Navarra
mesh_terms: D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001483:Base Sequence; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy; D015235:HLA-B Antigens / Q000097:blood / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D010597:Pharmacogenetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C484830:HLA-B*57:01 antigen