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 preexisting 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.
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Acknowledgements
This study was funded by GlaxoSmithKline, Inc. (Research Triangle Park, NC, USA).
Dr Kauf is an Associate Professor of Pharmaceutical Outcomes and Policy at the University of Florida. She received funding for this and other studies from GlaxoSmithKline and other pharmaceutical companies that market drugs for use in the treatment of HIV patients. Drs Earnshaw and Farkouh are employees of RTI Health Solutions, an independent contract research organization that has received research funding for this and other studies from GlaxoSmithKline and other pharmaceutical companies that market drugs for use in HIV patients and other medical conditions. Dr Watson, Ms Maroudas and Mr Chambers are full-time employees of GlaxoSmithKline, which manufacturers abacavir sulfate, zidovudine, lamivudine and various fixed-dose combinations of these drugs.
The individual authors’ contributions to the work are as follows: Dr Kauf led the study design, interpretation of results and writing and takes full responsibility for the content of the manuscript. Dr Farkouh conducted all data analysis and contributed to the interpretation of results and writing. Dr Earnshaw assisted with data management and analysis. Dr Watson, Ms Maroudas and Mr Chambers contributed to the interpretation of results and writing.
The authors would like to extend their thanks to the members of the expert panel, Dr Benjamin Young, Dr Trevor Hawkins, Dr Princy Kumar, Dr Edwin DeJesus and Dr Charles Hicks, for their invaluable contributions to this study.
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Kauf, T.L., Farkouh, R.A., Earnshaw, S.R. et al. Economic Efficiency of Genetic Screening to Inform the Use of Abacavir Sulfate in the Treatment of HIV. Pharmacoeconomics 28, 1025–1039 (2010). https://doi.org/10.2165/11535540-000000000-00000
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DOI: https://doi.org/10.2165/11535540-000000000-00000