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 Euro 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.
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 abacavirhypersensitivity 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 abacavirhypersensitivity 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 abacavirhypersensitivity, 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 abacavirhypersensitivepatients, six (46%) were HLA B*5701 positive, compared to five (10%) of the non-hypersensitivepatients (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 Euro 22,811 per hypersensitivity reaction avoided. CONCLUSIONS:Abacavirhypersensitivity is associated with HLA B*5701, and pre-prescription pharmacogenetic testing for this appears to be a cost-effective use of healthcare resources.
Authors: Hugues Aschard; Jinbo Chen; Marilyn C Cornelis; Lori B Chibnik; Elizabeth W Karlson; Peter Kraft Journal: Am J Hum Genet Date: 2012-05-24 Impact factor: 11.025
Authors: Mark McCormack; Ana Alfirevic; Stephane Bourgeois; John J Farrell; Dalia Kasperavičiūtė; Mary Carrington; Graeme J Sills; Tony Marson; Xiaoming Jia; Paul I W de Bakker; Krishna Chinthapalli; Mariam Molokhia; Michael R Johnson; Gerard D O'Connor; Elijah Chaila; Saud Alhusaini; Kevin V Shianna; Rodney A Radtke; Erin L Heinzen; Nicole Walley; Massimo Pandolfo; Werner Pichler; B Kevin Park; Chantal Depondt; Sanjay M Sisodiya; David B Goldstein; Panos Deloukas; Norman Delanty; Gianpiero L Cavalleri; Munir Pirmohamed Journal: N Engl J Med Date: 2011-03-24 Impact factor: 91.245
Authors: D F Heitjan; D A Asch; Riju Ray; Margaret Rukstalis; Freda Patterson; C Lerman Journal: Pharmacogenomics J Date: 2008-03-18 Impact factor: 3.550