title: Cost-effectiveness analysis of UGT1A1 genetic testing to inform antiretroviral prescribing in HIV disease.
abstract: BACKGROUND
  Homozygosity for UGT1A1*28/*28 has been reported to be associated with atazanavir-associated hyperbilirubinaemia and premature atazanavir discontinuation. We assessed the potential cost-effectiveness of UGT1A1 testing to inform the choice of an initial protease-inhibitor-containing regimen in antiretroviral therapy (ART)-naive individuals.
  
  
  METHODS
  We used the Cost-Effectiveness of Preventing AIDS Complications computer simulation model to project quality-adjusted life years (QALYs) and lifetime costs (2009 USD) for atazanavir-based ART with or without UGT1A1 testing, using darunavir rather than atazanavir when indicated. We assumed the UGT1A1-associated atazanavir discontinuation rate reported in the Swiss HIV Cohort Study (a *28/*28 frequency of 14.9%), equal efficacy and cost of atazanavir and darunavir and a genetic assay cost of $107. These parameters, as well as the effect of hyperbilirubinaemia on quality of life and loss to follow up, were varied in sensitivity analyses. Costs and QALYs were discounted at 3% annually.
  
  
  RESULTS
  Initiating atazanavir-based ART at CD4(+) T-cell counts <500 cells/μl without UGT1A1 testing had an average discounted life expectancy of 16.02 QALYs and $475,800 discounted lifetime cost. Testing for UGT1A1 increased QALYs by 0.49 per 10,000 patients tested and was not cost-effective (>$100,000/QALY). Testing for UGT1A1 was cost-effective (<$100,000/QALY) if assay cost decreased to $10, or if avoiding hyperbilirubinaemia by UGT1A1 testing reduced loss to follow-up by 5%. If atazanavir and darunavir differed in cost or efficacy, testing for UGT1A1 was not cost-effective under any scenario.
  
  
  CONCLUSIONS
  Testing for UGT1A1 may be cost-effective if assay cost is low and if testing improves retention in care, but only if the comparator ART regimens have the same drug cost and efficacy.
authors.affiliation: Department of Public Health, Weill Cornell Medical College, New York, NY, USA. brs2006@med.cornell.edu
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Schackman
authors.forename: David W
authors.initials: DW
authors.lastname: Haas
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Becker
authors.forename: Bethany K
authors.initials: BK
authors.lastname: Berkowitz
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sax
authors.forename: Eric S
authors.initials: ES
authors.lastname: Daar
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ribaudo
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Freedberg
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000191:economics; D003362:Cost-Benefit Analysis; D005260:Female; D005820:Genetic Testing / Q000191:economics; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019057:Quality-Adjusted Life Years
chemical_list: D014453:Glucuronosyltransferase