Presence of the CYP2B6 516G>T polymorphism and increased plasma Efavirenz concentrations in South African HIV infected patients
Date
2011-03-31
Authors
Gounden, Verena
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Abstract
Introduction
The 516G>T polymorphism in exon 4 of the CYP2B6 gene has been linked to
increased plasma Efavirenz (EFV) levels. EFV levels can predict therapeutic
efficacy and are related to the likelihood of developing adverse central nervous
system (CNS) effects. The aims of this study were to a) determine the presence of
the 516G>T and other possible CYP2B6 exon 4 polymorphisms in a South African
group of HIV-infected individuals and b) to investigate the relationship between the
EFV plasma concentrations, the CYP2B6 516G>T polymorphism and the
occurrence of CNS related side effects in this group of patients.
Methods
Data from 80 patients are presented. Genetic polymorphisms in exon 4 of the
CYP2B6 gene were identified using PCR amplification of this region followed by
sequencing of the amplification products. EFV levels were analysed by Ultra
performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).
Assessment of the presence of CNS related side effects following EFV initiation were
elicited with the use of a questionnaire together with physical examination.
Results
Plasma EFV concentrations displayed high inter-individual variability amongst
subjects with levels ranging from 94 μg /l to 23227 μg/l. 23 % of patients were TT
homozygous for the 516G>T polymorphism. These patients had significantly higher
EFV levels vs. those with the wild (GG) genotype (p <0.05). Those who experienced
no side effects had significantly lower EFV plasma concentrations vs. the group
which experienced the most severe side effects (p< 0.05).
iv
Conclusion
The significant association between the 516G>T polymorphism and plasma EFV
concentrations has been demonstrated in a South African cohort. A rapid and
sensitive method for the measurement of plasma EFV was developed and validated.
Description
MMed, Chemical Pathology, Faculty of Health Sciences, University of the Witwatersrand
Keywords
HIV, polymorphism, plasma Efavirenz concentrations