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Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population.


ABSTRACT:

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.

SUBMITTER: Carr DF 

PROVIDER: S-EPMC3616517 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Association of human leukocyte antigen alleles and nevirapine hypersensitivity in a Malawian HIV-infected population.

Carr Daniel F DF   Chaponda Mas M   Jorgensen Andrea L AL   Castro Elena Cornejo EC   van Oosterhout Joep J JJ   Khoo Saye H SH   Lalloo David G DG   Heyderman Robert S RS   Alfirevic Ana A   Pirmohamed Munir M  

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20130129 9


<h4>Background</h4>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  ...[more]

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