Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV‐infected patients in Uganda

Objectives Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV‐infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this p...

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Published in:HIV medicine 2007-03, Vol.8 (2), p.86-91
Main Authors: Penzak, SR, Kabuye, G, Mugyenyi, P, Mbamanya, F, Natarajan, V, Alfaro, RM, Kityo, C, Formentini, E, Masur, H
Format: Article
Language:English
Subjects:
Adult
Africa
Aryl Hydrocarbon Hydroxylases - genetics
Cohort Studies
CYP2B6
Cytochrome P-450 CYP2B6
Female
Genotype
HIV
HIV Infections - blood
HIV Infections - drug therapy
HIV Infections - epidemiology
Humans
Male
Middle Aged
nevirapine
Nevirapine - blood
Nevirapine - therapeutic use
Oxidoreductases, N-Demethylating - genetics
pharmacogenomics
Pilot Projects
Polymorphism, Genetic
Reverse Transcriptase Inhibitors - blood
Reverse Transcriptase Inhibitors - therapeutic use
Sex Distribution
Uganda - epidemiology
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Summary:Objectives Polymorphisms in the cytochrome P450 (CYP) 2B6 gene have been shown to influence nevirapine plasma concentrations in HIV‐infected European Caucasians. Although nevirapine is used extensively in Africa, the influence of CYP2B6 genotype on nevirapine exposure has not been assessed in this population. We aimed to determine the influence of CYP2B6 genotype at position 516 on nevirapine trough concentrations in HIV‐infected patients in Kampala, Uganda. Additional polymorphisms in the CYP and multidrug resistance protein‐1 (MDR‐1) genes were also assessed for their impact on nevirapine concentrations. Methods The following genotypes were determined in all subjects using polymerase chain reaction–restriction fragment length polymorphism: CYP2B6 G516T, MDR‐1 C3435T and G2677T, CYP3A4*1B and CYP3A5*3. Nevirapine plasma concentrations were determined using high‐performance liquid chromatography in 23 HIV‐infected patients who were generally healthy and had been taking nevirapine 200 mg twice daily for at least 14 days. Analysis of variance with post hoc testing was used to compare nevirapine concentrations among CYP2B6 genotype groups. Results The median nevirapine trough concentration in individuals homozygous for the variant allele (TT) was 7607 ng/mL vs 4181 and 5559 ng/mL for GG and GT individuals, respectively (GG vs TT median ratio=1.82; P=0.011). The mean ratio for TT vs GG individuals (95% confidence interval) was 1.51 (1.18, 1.84). No associations were observed between the other polymorphisms studied and nevirapine concentrations. Conclusions CYP2B6 G516T significantly influenced nevirapine trough concentrations in HIV‐infected patients in Uganda. Additional studies in larger patient populations are necessary to further define the potential clinical impact of these preliminary findings.
ISSN:1464-2662
1468-1293
DOI:10.1111/j.1468-1293.2007.00432.x