Purpose: We assessed the potential cost-effectiveness of UGT1A1 genetic testing to inform choice of the initial protease inhibitor-containing regimen in antiretroviral therapy (ART)-naïve HIV-infected individuals. Homozygosity for UGT1A1*28/*28 (Gilbert's variant) has been reported to predict abnormal liver tests and mild jaundice (hyperbilirubinemia) associated with the protease inhibitor drug atazanavir and premature atazanavir discontinuation.
Methods: The Cost-Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model projected quality-adjusted life years (QALYs) and lifetime costs (2009 US dollars) for atazanavir-based ART with or without UGT1A1 testing, using the protease inhibitor darunavir rather than atazanavir when indicated. We assumed UGT1A1-associated atazanavir discontinuation rates as reported in the Swiss HIV Cohort study, a *28/*28 frequency of 14.9%, equal efficacy and cost of atazanavir and darunavir, and genetic assay cost of $107. Sensitivity analyses varied these inputs, hyperbilirubinemia impact on quality of life, and loss to follow-up (LTFU). Costs and QALYs were discounted at 3% annually.
Results: Initiating atazanavir-based ART among patients eligible for ART (<500 CD4 cells/mm3) without UGT1A1 testing had an average discounted life expectancy of 16.02 QALYs and $530,700 discounted lifetime cost. Testing for UGT1A1 increased QALYs by 0.49 per 10,000 patients tested, and was not cost-effective (>$100,000/QALY) in the base case. Testing for UGT1A1 was cost-effective (<$100,000/QALY) if assay cost was reduced to $10 (Figure) or if avoiding toxicity by UGT1A1 testing reduced LTFU 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 regimens have the same drug cost and efficacy.