ArticleProceedings of the National Academy of Sciences of the United States of America2004
Predisposition to abacavir hypersensitivity conferred by HLA-B*5701 and a haplotypic Hsp70-Hom variant.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 9 of them syntheses that pooled it.
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Who cites it
112 citing papers in PubMed, 9 syntheses or guidelines pooled it, 442 citations in OpenAlex.
- Diagnostic Test Criteria for HLA Genotyping to Prevent Drug Hypersensitivity Reactions: A Systematic Review of Actionable HLA Recommendations in CPIC and DPWG Guidelines.Frontiers in pharmacology · 2020Pooled it
- Genetic testing for prevention of severe drug-induced skin rash.The Cochrane database of systematic reviews · 2019Pooled it
- Associations between human leukocyte antigen polymorphisms and hypersensitivity to antiretroviral therapy in patients with human immunodeficiency virus: a meta-analysis.BMC infectious diseases · 2019Pooled it
- Abacavir Hypersensitivity Reaction Reporting Rates During a Decade of HLA-B*5701 Screening as a Risk-Mitigation Measure.Pharmacotherapy · 2019Pooled it
- Improving the Efficiency and Quality of the Value Assessment Process for Companion Diagnostic Tests: The Companion test Assessment Tool (CAT).Journal of managed care & specialty pharmacy · 2015Pooled it
- Clinical Pharmacogenetics Implementation Consortium guidelines for HLA-B genotype and carbamazepine dosing.Clinical pharmacology and therapeutics · 2013Guideline
- A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci.Nature genetics · 2013Pooled it
- Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitization.Nature genetics · 2013Pooled it
- Clinical pharmacogenetics implementation consortium guidelines for HLA-B genotype and abacavir dosing.Clinical pharmacology and therapeutics · 2012Guideline
- Pharmacogenomics of antibacterial and antiviral therapies: Clinical actionability, evidence gaps, and future directions.Pharmacological reviews · 2026Review
- Advances in HIV Treatment and Vaccine Development: Emerging Therapies and Breakthrough Strategies for Long-Term Control.AIDS research and treatment · 2025Review
- HLA-B*57:01-dependent intracellular stress in keratinocytes triggers dermal hypersensitivity reactions to abacavir.PNAS nexus · 2024Article
- High-throughput, targeted MHC class I immunopeptidomics using a functional genetics screening platform.Nature biotechnology · 2023Article
- Allopurinol non-covalently facilitates binding of unconventional peptides to HLA-B*58:01.Scientific reports · 2023Article
- A Landscape of CRISPR/Cas Technique for Emerging Viral Disease Diagnostics and Therapeutics: Progress and Prospects.Pathogens (Basel, Switzerland) · 2022Review
- The Potential ofNutrients · 2022Review
- Modern developments in germline pharmacogenomics for oncology prescribing.CA: a cancer journal for clinicians · 2022Review
- Article
- Unravelling the Proteomics of HLA-B*57:01Journal of personalized medicine · 2022Article
- Distribution ofFrontiers in pharmacology · 2022Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Susceptibility to a clinically significant drug hypersensitivity syndrome associated with abacavir use seems to have a strong genetic component. We have previously shown that the presence of HLA-B*5701 strongly predicts abacavir hypersensitivity and have identified a potential susceptibility locus within a 300-kb region between the MEGT1 and C4A6 loci in the central MHC. We now report the results of fine recombinant genetic mapping in an expanded patient population of 248 consecutive, fully ascertained, abacavir-exposed individuals in the Western Australian HIV Cohort Study, in which 18 cases of definite abacavir hypersensitivity (7.3%) and 230 tolerant controls were identified. Haplotype mapping within patients with allelic markers of the 57.1 ancestral haplotype suggests a susceptibility locus within the 14-kb Hsp70 gene cluster. HLA-B*5701 was present in 94.4% of hypersensitive cases compared with 1.7% of controls (odds ratio, 960; P < 0.00001). A haplotypic nonsynonymous polymorphism of Hsp70-Hom (HspA1L, resulting from the substitution of residue M493T in the peptide-binding subunit) was found in combination with HLA-B*5701 in 94.4% of hypersensitive cases and 0.4% of controls (odds ratio, 3,893; P < 0.00001). Individuals with abacavir hypersensitivity demonstrated increased monocyte tumor necrosis factor expression in response to ex vivo abacavir stimulation, which was abrogated with CD8(+) T cell depletion. These data indicate that the concurrence of HLA-B*5701 and Hsp70-Hom M493T alleles is necessary for the development of abacavir hypersensitivity, which is likely to be mediated by an HLA-B*5701-restricted immune response to abacavir.
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