Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART

Munderi, Paula, Snowden, Wendy B., Walker, Ann Sarah, Kityo, Cissy, Mosteller, Michael, Kabuye, Geoffrey, Thoofer, Navdeep K., Ssali, Francis, Gilks, Charles F. and Hughes, Arlene R. (2011) Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART. Tropical Medicine and International Health, 16 2: 200-204. doi:10.1111/j.1365-3156.2010.02688.x


Author Munderi, Paula
Snowden, Wendy B.
Walker, Ann Sarah
Kityo, Cissy
Mosteller, Michael
Kabuye, Geoffrey
Thoofer, Navdeep K.
Ssali, Francis
Gilks, Charles F.
Hughes, Arlene R.
Title Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART
Journal name Tropical Medicine and International Health   Check publisher's open access policy
ISSN 1360-2276
1365-3156
Publication date 2011-02
Year available 2011
Sub-type Article (original research)
DOI 10.1111/j.1365-3156.2010.02688.x
Open Access Status
Volume 16
Issue 2
Start page 200
End page 204
Total pages 5
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing Ltd.
Collection year 2011
Language eng
Formatted 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. 
Keyword Aids
Pharmacogenetics
Drug hypersensitivity
African Continental Ancestry Group
Human Leukocyte Antigen B Asterisk 5701
Abacavir Hypersensitivity
Antiretroviral Therapy
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Public Health Publications
 
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