1. Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART.
- Author
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Munderi P, Snowden WB, Walker AS, Kityo C, Mosteller M, Kabuye G, Thoofer NK, Ssali F, Gilks CF, and Hughes AR
- Subjects
- Adult, Anti-HIV Agents therapeutic use, Dideoxynucleosides therapeutic use, Double-Blind Method, Drug Hypersensitivity etiology, Gene Frequency, Genetic Predisposition to Disease, Genotype, HIV Infections drug therapy, Humans, Nevirapine adverse effects, Nevirapine therapeutic use, Uganda, Anti-HIV Agents adverse effects, Dideoxynucleosides adverse effects, Drug Hypersensitivity genetics, HIV Infections genetics, HLA-B Antigens genetics
- Abstract
Objectives: To determine the frequencies of HLA-B alleles in Ugandan patients in the NORA substudy of the DART trial and to compare HLA-B allele frequencies in those with and without clinically diagnosed hypersensitivity reaction (HSR)., Methods: DNA-based HLA-B genotyping was used to determine HLA alleles in 247 participants who received abacavir, including all six participants ('cases') with clinically diagnosed abacavir HSR., Results: The incidence of clinical abacavir HSR in this double-blinded study was 2.0% (6/300) in the abacavir group. As HLA-B*5701 was absent throughout the entire cohort, including the six HSR 'cases', an association could not be established between HLA-B*5701 and clinically diagnosed abacavir HSR. No other HLA-B*57 alleles were present among the six 'cases'. HLA-B*5703 was the most frequent HLA-B*57 allele among the abacavir-tolerant participants., Conclusion: The rate of clinical HSR was low, which may reflect the expected 2-3% clinical false-positive rate seen in previous double-blind randomized studies. The presumption that these cases may be false-positive abacavir HSR is supported by the fact that no HLA-B*5701 alleles were found in the abacavir group. Implementation of prospective HLA-B*5701 screening must be based on benefit/risk considerations within local practice. Clinical risk management remains paramount., (© 2010 Blackwell Publishing Ltd.)
- Published
- 2011
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