DOI: 10.1097/fpc.0000000000000542 ISSN: 1744-6872

Prenatal efavirenz exposure is independently associated with maternal, but not fetal CYP2B6 genotype

Oluwasegun Eniayewu, Abdulafeez Akinloye, Babajide Shenkoya, Uche Azuka, Oluseye Bolaji, Ebunoluwa Adejuyigbe, Andrew Owen, Adeniyi Olagunju
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Objectives

Understanding the influence of fetal and maternal genetics on prenatal drug exposure could potentially improve benefit-risk evaluation. In this study, we investigated the impact of two functional polymorphisms in CYP2B6 on prenatal exposure to efavirenz.

Methods

Dried blood spot (DBS) samples were collected from HIV-positive pregnant women (n = 112) and their newborns (n = 107) at delivery. They were genotyped for single nucleotide polymorphisms in CYP2B6. Efavirenz was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results

Significant correlations were observed in efavirenz concentration between maternal and newborn (r = 0.46, R 2 = 0.21, P < 0.001), and maternal and cord (r = 0.83, R 2 = 0.68, P < 0.001) samples. Median (interquartile range) newborn plasma-to-maternal plasma and cord-to-maternal plasma ratios were 0.85 (0.03–3.49) and 0.78 (0.23–1.96), respectively. Newborn efavirenz concentration in DBS varied significantly based on composite maternal CYP2B6 genotype: fast (CYP2B6 516GG and 983TT, n = 26), 747 ng/ml (602–1060); intermediate (CYP2B6 516GT or 983TC n = 50), 1177 ng/ml (898–1765); and slow (CYP2B6 516GT and 983TC or 516TT or 983CC, n = 14), 3094 ng/ml (2126–3812). Composite newborn CYP2B6 genotype was, however, not significantly associated with prenatal exposure. Efavirenz concentration in newborn stratified as fast (n = 25), intermediate (n = 36), and slow metabolizers (n = 19) from prenatal exposure was 999.7 (774–1285), 1240 (709–1984), and 1792 ng/ml (1201–3188), respectively.

Conclusion

The clinical relevance of the observed influence of maternal genetics on prenatal efavirenz exposure requires further investigation.

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