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Association of Human Leukocyte Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected Population

Carr, DF, Chaponda, M, Jorgenen, A, Castro, EC, van Oosterhout, JJ, Khoo, S, Lalloo, David ORCID:, Heyderman, Robert, Alfirevic, A and Pirmohamed, M (2013) 'Association of Human Leukocyte Antigen Alleles and Nevirapine Hypersensitivity in a Malawian HIV-Infected Population'. Clinical Infectious Diseases, Vol 56, Issue 9, pp. 1330-1339.

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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.
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.
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.
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.

Item Type: Article
Subjects: WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Metabolic Diseases > General Metabolic Diseases > WD 320 Drug hypersensitivity
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 200 Leukocytes. Leukocyte disorders (General)
WR Dermatology > WR 140 Skin diseases (General)
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
Depositing User: Annmarie Hand
Date Deposited: 19 Dec 2013 11:59
Last Modified: 15 Jun 2018 14:44


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