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1. Ther Drug Monit. 2012 Feb 17. [Epub ahead of print]

Associations Between ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 Alleles in
Relation to Efavirenz and Nevirapine Pharmacokinetics in HIV-Infected

Heil SG, van der Ende ME, Schenk PW, van der Heiden I, Lindemans J, Burger D, van
Schaik RH.

From the Departments of *Clinical Chemistry (AKC); †Internal Medicine, Erasmus MC
University Medical Center Rotterdam, Rotterdam; ‡Department of Clinical Pharmacy,
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

BACKGROUND:: Human immunodeficiency virus (HIV)-infected individuals show large
interindividual variation in response to antiretroviral therapy. Efavirenz (EFV)
and nevirapine (NVP) are nonnucleoside reverse transcriptase inhibitors, which
are prescribed in combination with other antiretroviral therapy in so-called
highly active antiretroviral therapy. Recent studies provide evidence for the
role of cytochrome P450 (CYP) genes, in particular CYP2B6, in relation to EFV and
NVP pharmacokinetics. In this study, the authors investigated whether common
ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles are associated with plasma
concentrations of EFV and NVP in HIV-infected individuals. METHODS:: Plasma drug
concentrations were quantified by high-performance liquid chromatography in 143
HIV-infected individuals receiving either EFV or NVP. Genotyping for common
alleles was performed by restriction fragment length polymorphism and Taqman
assays. Individuals were genotyped for 11 single-nucleotide polymorphisms in 5
genes. CYP2B6 haplotypes were reconstructed by PHASE. RESULTS:: Plasma EFV
concentrations were positively associated with CYP2B6 c.516G>T, c.785A>G, and
c.983A>G single-nucleotide polymorphisms in HIV-infected individuals. Increased
plasma concentrations of EFV and NVP were present in individuals with the
CYP2B6*6/*6 or *6/*18 haplotype compared with CYP2B6*1/*1 [increase of 62% (95%
confidence interval, 44.0-80.1) and 24% (95% confidence interval, 7.0-40.0),
respectively, P < 0.01]. No significant association with other genes in relation
to EFV or NVP concentrations was found. CONCLUSIONS:: In this study, a strong
association of CYP2B6*6 and CYP2B6*18 alleles in relation to EFV and NVP plasma
concentrations was found, which confirmed previous studies.

PMID: 22354160 [PubMed - as supplied by publisher]