An Expanded Analysis of Pharmacogenetics Determinants of Efavirenz Response that Includes 3'-UTR Single Nucleotide Polymorphisms among Black South African HIV/AIDS Patients

Frontiers in Genetics
Marelize SwartCollet Dandara

Abstract

Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor prescribed as part of first-line highly active antiretroviral therapy (HAART) in South Africa. Despite administration of fixed doses of EFV, inter-individual variability in plasma concentrations has been reported. Poor treatment outcomes such as development of adverse drug reactions or treatment failure have been linked to EFV plasma concentrations outside the therapeutic range (1-4 μg/mL) in some studies. The drug metabolizing enzyme (DME), CYP2B6, is primarily responsible for EFV metabolism with minor contributions by CYP1A2, CYP2A6, CYP3A4, CYP3A5, and UGT2B7. DME coding genes are also regulated by microRNAs through targeting the 3'-untranslated region. Expanded analysis of 30 single nucleotide polymorphisms (SNPs), including those in the 3'-UTR, was performed to identify pharmacogenetics determinants of EFV plasma concentrations in addition to CYP2B6 c.516G>T and c.983T>C SNPs. SNPs in CYP1A2, CYP2B6, UGT2B7, and NR1I2 (PXR) were selected for genotyping among 222 Bantu-speaking South African HIV-infected patients receiving EFV-containing HAART. This study is a continuation of earlier pharmacogenetics studies emphasizing the role of genetic variation in the ...Continue Reading

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Citations

Sep 15, 2016·Omics : a Journal of Integrative Biology·Collen MasimirembwaPeter Derek Christian Leutscher
Dec 2, 2017·Journal of Personalized Medicine·Julie-Anne Tanner, Rachel F Tyndale
Mar 28, 2019·Expert Review of Clinical Pharmacology·Ramón CacabelosJuan C Carril
Feb 21, 2021·British Journal of Clinical Pharmacology·Ngah Kuan ChowAmer Hayat Khan

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis

Software Mentioned

Graphpad Prism
STATA
SHEsis
GraphPad
GeneMapper ©

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