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

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.

• Authors: Paula Munderi, Wendy B Snowden, Ann Sarah Walker, Cissy Kityo, Michael Mosteller, Geoffrey Kabuye, Navdeep K Thoofer, Francis Ssali, Charles F Gilks, Arlene R Hughes, DART Trial Team
• Journal: Tropical medicine & international health : TM & IH (Trop Med Int Health) Vol. 16 Issue 2 Pg. 200-4 (Feb 2011) ISSN: 1365-3156 [Electronic] England
• PMID: 21091860 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 Blackwell Publishing Ltd.

Chemical References

• Anti-HIV Agents
• Dideoxynucleosides
• HLA-B Antigens
• HLA-B*57:01 antigen
• Nevirapine
• abacavir

Topics

• Adult
• Anti-HIV Agents (adverse effects, therapeutic use)
• Dideoxynucleosides (adverse effects, therapeutic use)
• Double-Blind Method
• Drug Hypersensitivity (etiology, genetics)
• Gene Frequency
• Genetic Predisposition to Disease
• Genotype
• HIV Infections (drug therapy, genetics)
• HLA-B Antigens (genetics)
• Humans
• Nevirapine (adverse effects, therapeutic use)
• Uganda