Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients

Abstract

This is the first report that the 983T>C genotype (part of the CYP2B6*18 haplotype) impacts on nevirapine plasma concentrations and the first study to assess the impact of 983C homozygosity on efavirenz concentrations. These data have implications for administration of non-nucleoside reverse transcriptase inhibitors to Black patients.

Over Exposure to Efavirenz Plasma Concentrations among Beninese HIV Patients Treated by A 600 mg Daily Dose

“…Plasma concentration average of our population was 6,360 µg/L ± 539 µg/L. It is definitely higher than those found by Poeta and Wyen, which were respectively 2,200 and 2,077µg/L [15][16]. In the studies preceding ours, plasma concentrations averages were included in the therapeutic index described [1,000-4,000 µg/L].…”

African Genetic Diversity: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

“…The functional significance of most of these variants is not yet known (131). However, recent studies have shown that two polymorphisms (983T>C and 516G>T), found at a higher frequency in African populations relative to non-Africans, are associated with a reduction in CYP2B6 protein expression as well as a large increase in levels of the antiretroviral drug efavirenz in the plasma of African HIV patients (130,145,239).…”

The Pharmacogenetics of HIV Treatment: A Practical Clinical Approach

“…Subjects homozygous for the CYP2B6*6 allele, that contains both 516G>T and the 785A>G polymorphisms, display significantly higher EFV plasma levels than heterozygous subjects or those with the common genotype [10]. The 983T>C polymorphism, a less frequent polymorphism only described in Hispanic and black populations, has been shown to impact in EFV exposure as well [11,12]. In a recent study, Ribaudo et al [13] established that the CYP2B6*18 allele, that harbours the 516G>T and 983T>C polymorphisms, better predict EFV pharmacokinetics and also, slow-metabolizer genotypes were associated with increased CNS events among white patients and decreased virologic failure among black patients.…”

“…Several studies have reported that the polymorphisms 516G>T and 983T>C in the CYP2B6 gene are associated with variations in NVP pharmacokinetics in ethnically diverse populations [32][33][34][35][36], although the clinical impact remains uncertain since an association between greater NVP exposure and toxic effects has not been fully demonstrated.…”