WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Interindividual variability in efavirenz plasma concentrations is associated with CYP2B6 genetic polymorphisms.
• Twenty-nine different alleles of the CYP2B6 gene are listed. CYP2B6*6, *9, *16, *26, *27 and *28 carriers are reported to be associated with slower efavirenz oral clearance.
• The allelic variant 516G>T is associated with diminished activity of CYP2B6 and high efavirenz plasma concentrations are associated with an increase risk of neuropsychological toxicity.
WHAT THIS STUDY ADDS
• This study identified three SNPs in the CYP2B6 gene which could potentially act as additional independent predictors of efavirenz plasma concentrations beyond that provided by the CYP2B6 c.516G>T polymorphism.
• The GAC-CYP2B6 haplotype (G516T/A785G/C21563T) is associated with higher plasma efavirenz concentrations in HIV-infected Thai adults.
• The CYP2B6 g.18492 T>C polymorphism was significantly associated with lower efavirenz concentrations than those with the homozygous wild-type.
To investigate the frequency of CYP2B6 polymorphisms and the influence of haplotype structure on plasma efavirenz concentrations in Thai adults with HIV-1 infection.
Genotyping of nine single nucleotide polymorphisms (SNPs, c.64C>T, c.499C>G, c.516G>T, c.785A>G, c.1375A>G, c.1459C>T, g.3003T>C, g.18492C>T and g.21563C>T) of CYP2B6 were performed using real-time PCR-based allelic discrimination on blood samples from 52 HIV-infected adults who had received an efavirenz-based regimen. Plasma efavirenz concentrations were measured by high performance liquid chromatography.
The minor allele frequencies for c.64C>T, c.516G>T, c.785A>G, g.3003C>T, g.18492T>C and g.21563C>T were 0.087, 0.365, 0.413, 0.308 and 0.356, respectively. However, no variant alleles were identified for three SNPs (c.499 C>G, c.1375 A>G and c.1459 C>T). Efavirenz plasma concentrations were significantly associated with c.516G>T (P= 0.0095), c.785A>G (P= 0.0017), g.21563C>T (P= 0.0036) and g.18492C>T (P= 0.0011). The composite CYP2B6 of three SNPs (c.516G ≥ T, c.785A ≥ G and g.21563C ≥ T) genotypes were significantly associated with higher efavirenz concentrations.
Our data indicate that the GAC-CYP2B6 haplotype is associated with higher plasma efavirenz concentrations in HIV-infected Thai adults.