presence of the cyp2b6 516g t polymorphism, increased plasma efavirenz concentrations and early neuropsychiatric side effects in south african hiv-infected patientscyp2b6 516 g t多态性,增加依法韦伦血浆浓度和早期神经副作用在南非艾滋病病毒感染者.pdfVIP

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2017-09-11 发布于上海
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presence of the cyp2b6 516g t polymorphism, increased plasma efavirenz concentrations and early neuropsychiatric side effects in south african hiv-infected patientscyp2b6 516 g t多态性,增加依法韦伦血浆浓度和早期神经副作用在南非艾滋病病毒感染者.pdf

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presence of the cyp2b6 516g t polymorphism, increased plasma efavirenz concentrations and early neuropsychiatric side effects in south african hiv-infected patientscyp2b6 516 g t多态性,增加依法韦伦血浆浓度和早期神经副作用在南非艾滋病病毒感染者

Gounden et al. AIDS Research and Therapy 2010, 7:32 /content/7/1/32 RESEARCH Open Access Presence of the CYP2B6 516G T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients Verena Gounden 1,2*, Chantal van Niekerk1,2, Tracy Snyman1,2, Jaya A George1,2 Abstract Background: The 516G T polymorphism in exon 4 of the CYP2B6 gene has been associated with increased plasma Efavirenz (EFV) concentrations. EFV concentrations greater than the recommended therapeutic range have been associated with the increased likelihood of developing adverse CNS effects. The aims of this study were to a) determine the presence of the 516G T and other CYP2B6 exon 4 polymorphisms in a South African group of HIV- infected individuals b) investigate the relationship between the EFV plasma concentrations, the CYP2B6 516G T polymorphism and the occurrence of CNS related side effects in this group of patients and c) develop and validate a rapid method for determination of EFV in plasma. Method: Data from 80 patients is presented. Genetic polymorphisms in exon 4 of the CYP2B6 gene were identified using PCR amplification of this region followed by sequencing of the amplification products. EFV concentrations were analysed by UPLC-MS/MS. Assessment of the presence of CNS related side effects following EFV initiation were elicited with the use of a questionnaire together with physical examination. Results: Plasma EFV concentrations displayed high inter-individual variability amongst subjects with concentrations ranging from 94 μg/l to 23227 μg/l at 2 weeks post initiation of treatment. For the 516G T polymorphism the following frequencies were observed 23% of patients were TT homozygous, 36% GG and 41% GT. The TT homozygous patients had significantly higher