CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations

Carr, DF, Chaponda, M, Cornejo Castro, EM, Jorgensen, AL ORCID: 0000-0002-6977-9337, Khoo, S ORCID: 0000-0002-2769-0967, Van Oosterhout, JJ, Dandara, C, Kampira, E, Ssali, F, Munderi, P
et al (show 3 more authors) (2014) CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations. Journal of Antimicrobial Chemotherapy, 69 (12). pp. 3329-3334.

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Background Nevirapine, an NNRTI used in HIV treatment, can cause hypersensitivity reactions in 6%–10% of patients. In the most serious cases (1.3%) this can manifest as Stevens–Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). Methods DNA samples were obtained and analysed from a total of 209 adult patients with nevirapine hypersensitivity (57 from a prospective cohort and 152 routine clinic patients) and compared with 463 control patients on nevirapine without any hypersensitivity. The case group included 70 patients with SJS/TEN. All individuals were genotyped for two SNPs in the CYP2B6 gene [c.516G>T (CYP2B6*9) and c.983T>C (CYP2B6*18)] using the TaqMan real-time genotyping platform. The replication cohort comprised 29 controls and 55 nevirapine hypersensitive patients, including 8 SJS/TEN cases. Results An association between the CYP2B6 c.983T>C polymorphism and nevirapine-induced SJS/TEN was observed. In the SJS/TEN group, 30% of individuals possessed at least one c.983T>C versus 16% in the tolerant group [P = 0.006; OR (95% CI) 2.24 (1.27–3.94)]. This association was not significant in the replication cohort [P = 0.075; OR (95% CI) 4.33 (0.80–23.57)]. Combined analysis resulted in an OR of 2.52 (95% CI 1.48–4.20; P = 0.0005) for the association of c.983T>C with SJS/TEN. No association was observed for c.983T>C with other hypersensitivity phenotypes and for CYP2B6 c.516G>T with any hypersensitivity phenotypes. Conclusions Our data show an association between the c.983T>C polymorphism and nevirapine-induced SJS/TEN. CYP2B6 c.983T>C has a frequency of 5%–10% in a variety of African populations, but is not observed in Caucasians, thus representing an ethnic-specific predisposing factor.

Item Type: Article
Uncontrolled Keywords: pharmacogenetics, adverse drug reactions, Stevens-Johnson syndrome, antiretroviral
Depositing User: Symplectic Admin
Date Deposited: 02 Dec 2014 11:04
Last Modified: 15 Dec 2022 11:29
DOI: 10.1093/jac/dku315
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