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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population
Clinical Infectious Diseases, Volume 56, No. 9, Year 2013
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Description
Background. The nonnucleoside reverse transcriptase inhibitor nevirapine is the cornerstone of treatment for human immunodeficiency virus (HIV) in many sub-Saharan African countries. However, nevirapine is associated with a 6%-10% risk of developing a hypersensitivity reaction, with different phenotypes, including the blistering conditions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Our aim was to identify predictive human leukocyte antigen (HLA) markers that are associated with nevirapine hypersensitivity. Methods. We identified 117 HIV-infected Malawian adults with nevirapine hypersensitivity (15 drug-induced liver injury [DILI], 33 SJS/TEN, 20 hypersensitivity syndrome, and 46 nevirapine-induced rash plus 3 with both DILI and SJS phenotype) and 155 age-, sex-and ethnicity-matched nevirapine-exposed controls. HLA typing for 5 loci (A, B, C, DRB1, and DQB1) was undertaken using a sequence-based high-resolution protocol. Logistic regression analysis included CD4+ cell count as a covariate.Results. HLA-C*04:01 was found to markedly increase the risk for SJS (odds ratio [OR] = 17.52; 95% confidence interval, 3.31-92.80) and all hypersensitivity phenotypes (OR = 2.64; 95% CI, 1.13-6.18) when compared to the baseline rare allele group in a binary logistic regression model. The OR for absolute risk of SJS/TEN associated with carriage of HLA-C*04:01 was 5.17 (95% CI, 2.39-11.18). Positive predictive value was 2.6% and negative predictive value was 99.2%. In addition, a number of alleles within the HLA-DQB1 loci protected against nevirapine-induced hypersensitivity phenotypes.Conclusions. Our study has identified HLA-C*04:01 carriage as a risk factor for nevirapine-induced SJS/TEN in a Malawian HIV cohort. Validation of these findings in a larger cohort of patients and mechanistic investigation of the pathogenesis are required. © 2012 The Author.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3616517/bin/supp_56_9_1330__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3616517/bin/supp_cit021_cit021supp.doc
Authors & Co-Authors
Carr, Daniel F.
United Kingdom, Liverpool
University of Liverpool
Chaponda, Mas E.
United Kingdom, Liverpool
University of Liverpool
Malawi, Blantyre
Malawi-liverpool-wellcome Trust Clinical Research Programme
Jorgensen, Andrea Lyn
United Kingdom, Liverpool
University of Liverpool
Castro, Elena Cornejo
United Kingdom, Liverpool
University of Liverpool
van Oosterhout, Joep J.G.
Malawi, Blantyre
Malawi-liverpool-wellcome Trust Clinical Research Programme
Malawi, Zomba
University of Malawi
Khoo, Saye Hock
United Kingdom, Liverpool
University of Liverpool
Lalloo, David G.
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Heyderman, Robert Simon
Malawi, Blantyre
Malawi-liverpool-wellcome Trust Clinical Research Programme
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Alfirevic, Ana
United Kingdom, Liverpool
University of Liverpool
Pirmohamed, Munir
United Kingdom, Liverpool
University of Liverpool
Statistics
Citations: 97
Authors: 10
Affiliations: 4
Identifiers
Doi:
10.1093/cid/cit021
ISSN:
10584838
e-ISSN:
15376591
Research Areas
Environmental
Genetics And Genomics
Infectious Diseases
Violence And Injury
Study Design
Cross Sectional Study
Cohort Study
Case-Control Study
Study Approach
Quantitative