English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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.   Methods:  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 3′-UTR of genes which products are either pharmacokinetic or pharmacodynamic targets of EFV.   Results:  Despite evaluating thirty SNPs,  CYP2B6 c.516G > T  and  c.983T > C  SNPs remain the most prominent predictors of EFV plasma concentration.   Conclusion:  We have shown that  CYP2B6 c.516G > T  and  c.983T > C  SNPs are the most important predictors of EFV plasma concentration after taking into account all other SNPs, including genetic variation in the 3′-UTR, and variables affecting EFV metabolism.

frontiers in genetics

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