title: Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity.
abstract: OBJECTIVE
  Abacavir, a human immunodeficiency virus-1 (HIV-1) nucleoside-analogue reverse transcriptase inhibitor, causes severe hypersensitivity in 4-8% of patients. HLA B*5701 is a known genetic risk factor for abacavir hypersensitivity in Caucasians. Our aim was to confirm the presence of this genetic factor in our patients, and to determine whether genotyping for HLA B*5701 would be a cost-effective use of healthcare resources.
  
  
  METHODS
  Patients with and without abacavir hypersensitivity were identified from a UK HIV clinic. Patients were genotyped for HLA B*5701, and pooled data used for calculation of test characteristics. The cost-effectiveness analysis incorporated the cost of testing, cost of treating abacavir hypersensitivity, and the cost and selection of alternative antiretroviral regimens. A probabilistic decision analytic model (comparing testing versus no testing) was formulated and Monte Carlo simulations performed.
  
  
  RESULTS
  Of the abacavir hypersensitive patients, six (46%) were HLA B*5701 positive, compared to five (10%) of the non-hypersensitive patients (odds ratio 7.9 [95% confidence intervals 1.5-41.4], P = 0.006). Pooling of our data on HLA B*5701 with published data resulted in a pooled odds ratio of 29 (95% CI 6.4-132.3; P < 0.0001). The cost-effectiveness model demonstrated that depending on the choice of comparator, routine testing for HLA B*5701 ranged from being a dominant strategy (less expensive and more beneficial than not testing) to an incremental cost-effectiveness ratio (versus no testing) of Euro 22,811 per hypersensitivity reaction avoided.
  
  
  CONCLUSIONS
  Abacavir hypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L69 3GE, UK.
authors.forename: Dyfrig A
authors.initials: DA
authors.lastname: Hughes
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Vilar
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Ward
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
authors.forename: B Kevin
authors.initials: BK
authors.lastname: Park
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
mesh_terms: D000328:Adult; D003362:Cost-Benefit Analysis; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000191:economics*; D004342:Drug Hypersensitivity / Q000191:economics* / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000191:economics* / Q000276:immunology; D015497:HIV-1; D015235:HLA-B Antigens / Q000191:economics* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000191:economics; D009010:Monte Carlo Method; D016017:Odds Ratio; D010597:Pharmacogenetics / Q000191:economics; D019095:Point-of-Care Systems / Q000191:economics; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000191:economics*; D012307:Risk Factors; D000099227:Abacavir
chemical_list: D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C484830:HLA-B*57:01 antigen