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dc.contributor.authorReay, Riaan
dc.contributor.authorViljoen, Michelle
dc.contributor.authorRheeders, Malie
dc.contributor.authorDandara, Collet
dc.date.accessioned2017-09-05T06:14:26Z
dc.date.available2017-09-05T06:14:26Z
dc.date.issued2017
dc.identifier.citationReay, R. et al. 2017. CYP2B6 haplotype predicts efavirenz plasma concentration in black South African HIV-1-infected children: a longitudinal pediatric pharmacogenomic study. Omics: a journal of integrative biology, 21(8):465-473. [https://doi.org/10.1089/omi.2017.0078]en_US
dc.identifier.issn1536-2310
dc.identifier.issn1557-8100 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/25490
dc.identifier.urihttp://online.liebertpub.com/doi/abs/10.1089/omi.2017.0078
dc.identifier.urihttps://doi.org/10.1089/omi.2017.0078
dc.description.abstractSouth Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa. We characterized the HIV-1-infected children (n = 60) for the CYP2B6 c.516G>T, c.785A>G, c.983T>C, and c.1459C>T single nucleotide polymorphisms (SNPs). These SNPs were determined using polymerase chain reaction/restricted fragment length polymorphism and SNaPshot genotyping. Longitudinal mid-dose EFV plasma concentrations were determined by LC-MS/MS and association analyses with genotypes and haplotypes at 1, 3, and 24 months were performed. The CYP2B6 c.516T/T genotype showed significantly higher EFV plasma concentrations (p < 0.001) compared to non 516T-allele carriers at all three time points. The minor allele frequencies (MAF) for CYP2B6 c.516T, c.785G, c.983C, and c.1459T were 0.410, 0.408, 0.110, and 0.000 respectively. Haplotypes were constructed using CYP2B6 c.516G>T,–c.785A>G and c.983T>C. The haplotype T-G-T presented with significantly increased EFV plasma concentrations compared to the reference G-A-T haplotype at 1, 3, and 24 months (p = 0.009; p = 0.003; p = 0.001), suggesting that the T-G-T haplotype predisposes a risk of EFV plasma concentrations >4 μg/mL. The clinical implications of these pharmacogenomics observations for EFV toxicity and treatment resistance warrant further future researchen_US
dc.language.isoenen_US
dc.publisherMary Ann Lieberten_US
dc.subjectEfavirenzen_US
dc.subjectPediatricsen_US
dc.subjectCYP2B6en_US
dc.subjectHaplotypesen_US
dc.subjectPharmacogenomicsen_US
dc.titleCYP2B6 haplotype predicts efavirenz plasma concentration in black South African HIV-1-infected children: a longitudinal pediatric pharmacogenomic studyen_US
dc.typeArticleen_US
dc.contributor.researchID10064117 - Rheeders, Malie
dc.contributor.researchID10215344 - Viljoen, Michelle
dc.contributor.researchID12529524 - Reay, Riaan


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