Influence of 516G&gt;T Polymorphisms at the Gene Encoding the CYP450-2B6 Isoenzyme on Efavirenz Plasma Concentrations in HIV-Infected Subjects

Rodrı́guez-Nóvoa, Sonia; Barreiro, Pablo; Rendón, Ana; Jiménez-Nácher, Inmaculada; González-Lahoz, Juan; Soriano, Vincent

doi:10.1086/429327

Cited by 172 publications

(124 citation statements)

References 12 publications

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“…Several studies [8][9][10][11][12][13][14] reported an association between the CYP2B6 G516T and A785G single nucleotide polymorphisms (SNPs) and the rate of plasma clearance of efavirenz and occurrence of related ADRs.…”

Section: Cyp2b6mentioning

confidence: 99%

A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups

Gebhardt

et al. 2009

J Hum Genet

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South Africa, like many other Southern African countries, has one of the highest HIV infection rates in the world and many individuals consequently receive antiretroviral therapy (ART). However, knowledge regarding (i) the prevalence of functional single nucleotide polymorphisms (SNPs) in pharmacologically relevant genes, and (ii) variance in pharmacotherapy both within and between different populations and ethnic groups is limited. The aim of this study was to determine whether selected polymorphisms in cytochrome P450 (CYP) genes (CYP2B6 and CYP3A4) and the multidrug-resistance 1 (ABCB1) gene underlie altered antiretroviral (ARV) drug response in two South African populations. DNA samples from 182 HIV-positive individuals of Mixed-Ancestry and Xhosa ethnicity on ART were genotyped for the A-392G SNP in CYP3A4, the G516T and A785G SNPs in CYP2B6, and the T-129C, C1236T, G2677T/A and C3435T SNPs in ABCB1. Univariate two-way analysis of variance (ANOVA) testing revealed no apparent effect of ethnicity on immune recovery (in terms of CD4-cell count) in response to ART. Univariate one-way ANOVA testing revealed a discernible effect of genotype on immune recovery in the cases of the T-129C (P¼0.03) and G2677A (Po0.01) polymorphisms in the ABCB1 gene. This study serves as a basis for better understanding and possible prediction of pharmacogenetic risk profiles and drug response in individuals and ethnic groups in South Africa.

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Section: Cyp2b6mentioning

confidence: 99%

A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups

Gebhardt

et al. 2009

J Hum Genet

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“…Efavirenz-Several studies have identified a relationship between CYP2B6-G516T gene polymorphisms and plasma EFV pharmacokinetics in HIV-infected adults [13][14][15][16][17][18][19][20] and children [21] (Table 1). All available data have shown that the subjects with the CYP2B6-516-T/T genotype (homozygous variants) have consistently higher EFV concentrations compared to those with the CYP2B6-516-G/T (heterozygous variant) and G/ G genotype (wild type).…”

Section: Cyp2b6 Genotypes and Nnrti Pharmacokineticsmentioning

confidence: 99%

“…All available data have shown that the subjects with the CYP2B6-516-T/T genotype (homozygous variants) have consistently higher EFV concentrations compared to those with the CYP2B6-516-G/T (heterozygous variant) and G/ G genotype (wild type). Additional research also identified differences in EFV pharmacokinetics in subjects with the CYP2B6-516-G/T and those with the CYP2B6-516-G/ G genotypes [14,16,19,20].…”

Section: Cyp2b6 Genotypes and Nnrti Pharmacokineticsmentioning

confidence: 99%

“…Although there are a number of reasons for these differential responses, recent pharmacogenetic studies suggest that at least some of these variable responses to NNRTI containing regimens are predictable based on variants in genes responsible for metabolizing and transporting antiretrovirals including PIs, NNRTIs and NRTIs [12]. Compelling data, confirmed by several cohorts, demonstrate that the single nucleotide polymorphism (SNP) in CYP2B6 (CYP2B6-G516T or CYP2B6*6) significantly alters EFV pharmacokinetics in HIV-infected patients [13][14][15][16][17][18][19][20][21]. In addition, other studies have shown the importance of the CYP2B6 SNP on central nervous system (CNS) adverse effects related to EFV use [14,15] and NVP pharmacokinetics [15,22,23].…”

Section: Introductionmentioning

confidence: 99%

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Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of Nnrtis

Saitoh

Spector

2007

Future HIV Ther.

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Non-nucleoside reverse transcriptase inhibitors (NNRTIs) have been used widely for treating human immunodeficiency virus type 1 (HIV-1) infected patients as a component of highly active antiretroviral therapy (HAART) and for the prevention of mother-to-child transmission (MTCT). Cytochrome P450 (CYP) 2B6 is an important hepatic isoenzyme responsible for the metabolism of NNRTIs including efavirenz and nevirapine. Recent pharmacogenetic studies have shown that CYP2B6 genetic variants alter hepatic CYP2B6 protein expression and function, and the pharmacokinetics of several CYP2B6 substrates. In particular, the CYP2B6-G516T polymorphism in exon 4 affects the pharmacokinetics of efavirenz. Other studies have shown associations of the CYP2B6-G516T genotype with nevirapine pharmacokinetics and central nervous system adverse effects related to efavirenz use. In total, CYP2B6 genetic variants are important determinants of efavirenz and nevirapine pharmacokinetics . Further studies are needed to identify the associations of CYP2B6 genetic variants with the development of NNRTI resistant viruses.

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“…Likewise, studies have also been done in African populations to evaluate the clinical implications of the CYP2B6*6 allele in the use of efavirenz [15][16][17][18], and nevirapine [19][20][21]. CYP2B6*6 has been associated with higher efavirenz plasma concentrations due to lower clearance rates, which may lead to CNS side effects [22,23].…”

Section: Introductionmentioning

confidence: 99%

CYP2B6*6 Screening; Potential Benefits and Challenges in HIV Therapy in Sub-Saharan Africa

Dhoro¹

2017

J Clin Cell Immunol

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CYP2B6*6 genotyping appears to be a promising approach towards the prediction of efavirenz toxicity and risk of developing resistant mutations to nevirapine. The use of cost-effective technologies to screen for the allele may therefore become part of routine clinical practice, for which benefits in terms of cost reduction for governments and patients are evident. However, pharmacogenomics has not yet lived up to its hype and benefits in both the developed and developing worlds in particular sub-Saharan Africa where access to basic healthcare services is limited. Although numerous reports have advocated for the implementation of CYP2B6*6-guided drug therapy in HIV patients receiving efavirenz or nevirapine, this has not been effected yet. The reasons require both practical and clinical considerations.

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Influence of 516G>T Polymorphisms at the Gene Encoding the CYP450-2B6 Isoenzyme on Efavirenz Plasma Concentrations in HIV-Infected Subjects

Cited by 172 publications

References 12 publications

A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups

A pharmacogenetic study of CD4 recovery in response to HIV antiretroviral therapy in two South African population groups

Effect of Host Genetic Variation on the Pharmacokinetics and Clinical Response of Nnrtis

CYP2B6*6 Screening; Potential Benefits and Challenges in HIV Therapy in Sub-Saharan Africa

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