Cost-effectiveness analysis of HLA B*5701 genotyping in... : Pharmacogenetics and Genomics (original) (raw)

ORIGINAL ARTICLES

Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity

Hughes, Dyfrig Aa; Vilar, F Javierb; Ward, Charlotte Ca; Alfirevic, Anaa; Park, B Kevina; Pirmohamed, Munira

aDepartment of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L69 3GE, UK and bDepartment of Infectious Diseases, North Manchester General Hospital, Manchester, M8 6RL, UK.

Correspondence and requests for reprints to Prof Munir Pirmohamed, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, L69 3GE, UK. Tel: +44 (0)151 794 5549; fax: +44 (0)151 794 5540; e-mail: [email protected]

Received 5 January 2004 Accepted 5 March 2004

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 €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.

© 2004 Lippincott Williams & Wilkins, Inc.

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