CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans.

OBJECTIVE

Efavirenz, an antiretroviral medicine, is extensively metabolized by cytochrome P450 2B6 (CYP2B6), UDP-glucuronosyltransferase 2B7 (UGT2B7), and CYP2A6. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean human immunodeficiency virus (HIV)-positive patients treated with efavirenz.

METHODS

The exon regions of the CYP2B6, CYP2A6, and UGT2B7 genes were re-sequenced in 49 HIV-infected Zimbabwean patients treated with a combination therapy including efavirenz. Associations of SNPs in these three genes with efavirenz plasma concentrations 11-16 h after the administration of treatment were evaluated.

RESULTS

Eight patients carrying CYP2B6*6/18 showed the highest plasma efavirenz levels, with a fourfold higher concentration than patients who carried CYP2B61/1. Patients with CYP2B66/6 also showed higher efavirenz plasma concentrations than those with CYP2B61/*1. Among the 17 and 12 SNPs identified in CYP2A6 and UGT2B7, respectively, no SNP showed a significant association with the plasma efavirenz concentration.

CONCLUSION

Although based on only a limited number of subjects, our results suggest that the CYP2B66 and CYP2B618 alleles should affect hepatic metabolic activity and elevate the systemic circulation level of efavirenz, which may lead to toxicity in Zimbabwean HIV patients.