Document Detail


The relationships of ABCB1 3435C>T and CYP2B6 516G>T with high-density lipoprotein cholesterol in HIV-infected patients receiving Efavirenz.
MedLine Citation:
PMID:  19474786     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are associated with a favorable increase in high-density lipoprotein cholesterol (HDL-c) level. Isolated studies have found a direct correlation between efavirenz (EFV) exposure and HDL-c level changes. Here we explore the impact that drug disposition variants associated with EFV exposure have on changes in HDL-c level. Seventy-six patients on first-line EFV-based regimens were genotyped for CYP2B6 516G>T and ABCB1 3435C>T. There was a 37% increase (+0.32 mmol/l, P < 0.001) in mean HDL-c level over 48 weeks, and this was univariately associated with gender (male +0.26 mmol/l, female +0.55 mmol/l; P = 0.03), ABCB1 3435C>T (CC +0.26 mmol/l, CT +0.16 mmol/l, TT +0.54 mmol/l; P(ANOVA) = 0.003) and CYP2B6 516 G>T (GG +0.27 mmol/l, GT +0.29 mmol/l, TT +0.72 mmol/l; P(ANOVA) = 0.08). There was a significant association between the cumulative number of predictive genotypes (CYP2B6 516TT or ABCB1 3435TT) and mean HDL-c level change: (group 0 +0.20 mmol/l, group 1 +0.47 mmol/l, group 2 +1.00 mmol/l; P(ANOVA) < 0.0001). These findings need to be validated in independent cohorts.
Authors:
T W Mahungu; D Nair; C J Smith; D Egan; M Youle; M A Johnson; S H Khoo; D J Back; A Owen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-27
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  86     ISSN:  1532-6535     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-07-21     Completed Date:  2009-08-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  204-11     Citation Subset:  AIM; IM    
Affiliation:
Department of HIV Medicine, Royal Free NHS Trust, London, UK. wambura@gmail.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Anti-HIV Agents / blood,  pharmacology*,  therapeutic use
Aryl Hydrocarbon Hydroxylases / genetics*
Benzoxazines / blood,  pharmacology*,  therapeutic use
Cholesterol, HDL / blood*
Female
Genotype
HIV Infections / blood*,  drug therapy*,  ethnology
Humans
Male
Middle Aged
Multivariate Analysis
Oxidoreductases, N-Demethylating / genetics*
P-Glycoprotein / genetics*
Polymorphism, Single Nucleotide*
Reverse Transcriptase Inhibitors / blood,  pharmacology*,  therapeutic use
Sex Factors
Time Factors
Chemical
Reg. No./Substance:
0/ABCB1 protein, human; 0/Anti-HIV Agents; 0/Benzoxazines; 0/Cholesterol, HDL; 0/P-Glycoprotein; 0/Reverse Transcriptase Inhibitors; 154635-17-3/efavirenz; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/S-mephenytoin N-demethylase; EC 1.5.-/Oxidoreductases, N-Demethylating

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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