Journal article
A simple screening approach to reduce B*5701-associated abacavir hypersensitivity on the basis of sequence variation in HIV reverse transcriptase
Clinical Infectious Diseases, Vol.44(11), pp.1503-1508
2007
Abstract
Background. Abacavir hypersensitivity is strongly associated with the human leukocyte antigen (HLA)–B*5701 allele; however, the cost of routine high-resolution HLA typing before initiation of therapy remains prohibitive. We propose a simple approach to reduce B*5701-associated abacavir hypersensitivity based on the screening of human immunodeficiency virus (HIV) reverse transcriptase (RT) for a signature B*5701-associated cytotoxic T lymphocyte escape mutation at RT codon 245.
Methods. The correlation between HLA-B*5701 and RT codon 245 variation was investigated in 392 HIV-infected, antiretroviral-naive adults who were initiating highly active antiretroviral therapy. The relationship between codon 245 variation and premature abacavir discontinuation was investigated in a larger cohort of treated individuals (n = 982). Associations between HLA-B*5701 and codon 245 variants were determined using Fisher's exact test or the χ2 test.
Results. A very strong association between HLA-B*5701 and RT codon 245 variation was observed. Only 1 (4.2%) of 24 subjects with B*5701 harbored virus with the clade B “wild-type” amino acid 245V, compared with 278 (75.5%) of 368 who did not have B*5701 (P < .001). The sensitivity and specificity of codon 245 substitutions for predicting HLA-B*5701 were 96% and 75%, respectively, and the positive and negative predictive values were 20% and 99.6%, respectively. This association remained robust even after antiretroviral treatment was administered (negative predictive value, 100%; n = 269). In abacavir-treated individuals (n = 982), codon 245 substitutions were predictive of premature abacavir discontinuation (P = .02).
Conclusions. As HIV RT sequence is incidentally obtained as a part of routine drug-resistance testing, the examination of sequence variation at RT codon 245 could be adopted as a simple, low-cost screening method to identify individuals who could be safely treated with abacavir and/or who could benefit from HLA characterization.
Details
- Title
- A simple screening approach to reduce B*5701-associated abacavir hypersensitivity on the basis of sequence variation in HIV reverse transcriptase
- Authors/Creators
- C.K.S. Chui (Author/Creator)Z.L. Brumme (Author/Creator)C.J. Brumme (Author/Creator)B. Yip (Author/Creator)E.J. Phillips (Author/Creator)J.S.G. Montaner (Author/Creator)P.R. Harrigan (Author/Creator)
- Publication Details
- Clinical Infectious Diseases, Vol.44(11), pp.1503-1508
- Publisher
- University of Chicago Press
- Identifiers
- 991005543425107891
- Copyright
- 2007 Infectious Diseases Society of America
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.265 Dermatology - Skin Allergies
- 1.265.1140 Drug Hypersensitivity
- Web Of Science research areas
- Immunology
- Infectious Diseases
- Microbiology
- ESI research areas
- Immunology