ArticleThe Journal of antimicrobial chemotherapy2017
Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- A resource for integrated genomic analysis of the human liver.Scientific reports · 2022Pooled it
- Introduction to Pharmacogenomics: Role of the Histocompatibility and Immunogenetics Laboratory in Personalised Medicine-Current Status and Future Prospects.International journal of immunogenetics · 2026Review
- Stevens-Johnson syndrome induced by fluoroquinolones in a patient with colon cancer: A case report and literature review.Experimental and therapeutic medicine · 2026Article
- Human leukocyte antigen pharmacogenetics in infectious diseases: anti-infective drug toxicity and host immune response.Frontiers in pharmacology · 2026Review
- Implementing health economics for pharmacogenomics research translation in Africa.Communications medicine · 2025Review
- The role of corticosterone in nevirapine-induced idiosyncratic drug-induced liver injury.Toxicological sciences : an official journal of the Society of Toxicology · 2024Article
- HLA-B*57:01-dependent intracellular stress in keratinocytes triggers dermal hypersensitivity reactions to abacavir.PNAS nexus · 2024Article
- Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases.Journal of personalized medicine · 2023Article
- Pharmacogenomics: current status and future perspectives.Nature reviews. Genetics · 2023Review
- Delayed Drug Hypersensitivity Reactions: Molecular Recognition, Genetic Susceptibility, and Immune Mediators.Biomedicines · 2023Review
- Article
- Practical Implementation of Genetics: New Concepts in Immunogenomics to Predict, Prevent, and Diagnose Drug Hypersensitivity.The journal of allergy and clinical immunology. In practice · 2022Article
- The Immunogenetics of Cutaneous Drug Reactions.Advances in experimental medicine and biology · 2022Article
- Evolution ofFrontiers in pharmacology · 2022Article
- Immunopharmacogenomics: Mechanisms of HLA-Associated Drug Reactions.Clinical pharmacology and therapeutics · 2021Review
- ERAPs Reduce In Vitro HIV Infection by Activating Innate Immune Response.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Genomic Risk Factors Driving Immune-Mediated Delayed Drug Hypersensitivity Reactions.Frontiers in genetics · 2021Review
- Review on Databases and Bioinformatic Approaches on Pharmacogenomics of Adverse Drug Reactions.Pharmacogenomics and personalized medicine · 2021Review
- Genetics of Severe Cutaneous Adverse Reactions.Frontiers in medicine · 2021Review
- Clinical and pathogenic aspects of the severe cutaneous adverse reaction epidermal necrolysis (EN).Journal of the European Academy of Dermatology and Venereology : JEADV · 2020Review
Corrections and comments
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Authors and funding
24 authors at 11 institutions in 7 countries.
Funding
Abstract
Background: The antiretroviral nevirapine is associated with hypersensitivity reactions in 6%-10% of patients, including hepatotoxicity, maculopapular exanthema, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Objectives: To undertake a genome-wide association study (GWAS) to identify genetic predisposing factors for the different clinical phenotypes associated with nevirapine hypersensitivity. Methods: A GWAS was undertaken in a discovery cohort of 151 nevirapine-hypersensitive and 182 tolerant, HIV-infected Malawian adults. Replication of signals was determined in a cohort of 116 cases and 68 controls obtained from Malawi, Uganda and Mozambique. Interaction with ERAP genes was determined in patients positive for HLA-C*04:01 . In silico docking studies were also performed for HLA-C*04:01 . Results: Fifteen SNPs demonstrated nominal significance ( P < 1 × 10 -5 ) with one or more of the hypersensitivity phenotypes. The most promising signal was seen in SJS/TEN, where rs5010528 ( HLA-C locus) approached genome-wide significance ( P < 8.5 × 10 -8 ) and was below HLA -wide significance ( P < 2.5 × 10 -4 ) in the meta-analysis of discovery and replication cohorts [OR 4.84 (95% CI 2.71-8.61)]. rs5010528 is a strong proxy for HLA-C*04:01 carriage: in silico docking showed that two residues (33 and 123) in the B pocket were the most likely nevirapine interactors. There was no interaction between HLA-C*04:01 and ERAP1 , but there is a potential protective effect with ERAP2 [ P = 0.019, OR 0.43 (95% CI 0.21-0.87)]. Conclusions: HLA-C*04:01 predisposes to nevirapine-induced SJS/TEN in sub-Saharan Africans, but not to other hypersensitivity phenotypes. This is likely to be mediated via binding to the B pocket of the HLA-C peptide. Whether this risk is modulated by ERAP2 variants requires further study.
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