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The Relationships of ABCB1 3435C>T and CYP2B6 516G>T With High‐Density Lipoprotein Cholesterol in HIV‐Infected Patients Receiving Efavirenz
Author(s) -
Mahungu TW,
Nair D,
Smith CJ,
Egan D,
Youle M,
Johnson MA,
Khoo SH,
Back DJ,
Owen A
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.78
Subject(s) - efavirenz , cyp2b6 , medicine , high density lipoprotein , pharmacology , reverse transcriptase inhibitor , human immunodeficiency virus (hiv) , cholesterol , endocrinology , chemistry , gastroenterology , metabolism , antiretroviral therapy , virology , viral load , cytochrome p450 , cyp3a4
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. Clinical Pharmacology & Therapeutics (2009); 86 , 2, 204–211 doi: 10.1038/clpt.2009.78