title: Economic efficiency of genetic screening to inform the use of abacavir sulfate in the treatment of HIV.
abstract: BACKGROUND
  Abacavir sulfate (abacavir) is associated with a hypersensitivity reaction (HSR) that affects 5-8% of patients. While serious complications are rare, failure to identify it, or abacavir re-challenge following HSR, can be fatal. Genetic screening for HLA-B*5701 can identify patients who are likely to experience an HSR and reduces the incidence of the reaction.
  
  
  OBJECTIVE
  We assessed the intrinsic and practical value, from the US healthcare system perspective, of prospective HLA-B*5701 screening among a population of antiretroviral-naive patients without elevated risk factors for cardiovascular disease, plasma HIV RNA >100,000 copies/mL, or pre-existing renal insufficiency.
  
  
  METHODS
  Two approaches were used to evaluate the costs and benefits of prospective screening. First, the efficiency of HLA-B*5701 screening compared with no screening prior to abacavir initiation (intrinsic value of screening) was evaluated using a 60-day decision-tree model. Next, the practical value of screening was assessed using a lifetime discrete-event simulation model that compared HLA-B*5701 screening prior to abacavir use versus initiation with a tenofovir-containing regimen. Screening-effectiveness parameters were taken from an open-label trial that incorporated screening prior to abacavir initiation and other published studies. Treatment efficacy was derived from clinical trials. Modelling assumptions, costs ($US, year 2007 values) and other parameters were derived from published sources, primary data analysis and expert opinion. Multiple one-way sensitivity and scenario analyses were performed to assess parameter uncertainty. The primary outcome measure for the short-term screening versus no screening analysis was cost per patient. For the long-term analysis, outcomes were presented as QALYs. Costs and effects were discounted at 3% per year.
  
  
  RESULTS
  Over the first 60 days of treatment, prospective screening prior to abacavir initiation cost an additional $US17 per patient and avoided 537 HSRs per 10,000 patients. The per-patient cost of screening was sensitive to the cost of the genetic test, HSR costs and screening performance. In the lifetime model, screening-informed abacavir use was more effective and less costly than initiation with a tenofovir-containing regimen in the base case and in sensitivity analyses.
  
  
  CONCLUSIONS
  Our results suggest that prospective HLA-B*5701 screening prior to abacavir initiation produces cost savings and should become a standard component of HIV care.
authors.affiliation: University of Florida, Gainesville, Florida, USA. tkauf@ufl.edu
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Kauf
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Farkouh
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Earnshaw
authors.forename: Maria E
authors.initials: ME
authors.lastname: Watson
authors.forename: Penny
authors.initials: P
authors.lastname: Maroudas
authors.forename: Mike G
authors.initials: MG
authors.lastname: Chambers
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000191:economics / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000191:economics; D003198:Computer Simulation; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000191:economics / Q000627:therapeutic use*; D004342:Drug Hypersensitivity / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000191:economics / Q000628:therapy; D005820:Genetic Testing / Q000191:economics*; D015658:HIV Infections / Q000188:drug therapy* / Q000191:economics*; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D018803:Models, Economic; D063065:Organophosphonates / Q000191:economics / Q000627:therapeutic use; D019057:Quality-Adjusted Life Years; D000068698:Tenofovir; D014481:United States; D000099227:Abacavir
chemical_list: D000225:Adenine; D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D063065:Organophosphonates; D000068698:Tenofovir; D000099227:Abacavir; C484830:HLA-B*57:01 antigen