Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
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Adult
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Alkynes
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Anti-HIV Agents / blood
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Anti-HIV Agents / pharmacology*
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Anti-HIV Agents / therapeutic use
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Aryl Hydrocarbon Hydroxylases / genetics*
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Benzoxazines / blood
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Benzoxazines / pharmacology*
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Benzoxazines / therapeutic use
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Cholesterol, HDL / blood*
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Cyclopropanes
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Cytochrome P-450 CYP2B6
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Female
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Genotype
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HIV Infections / blood*
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HIV Infections / drug therapy*
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HIV Infections / ethnology
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Humans
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Male
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Middle Aged
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Multivariate Analysis
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Oxidoreductases, N-Demethylating / genetics*
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Polymorphism, Single Nucleotide*
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Reverse Transcriptase Inhibitors / blood
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Reverse Transcriptase Inhibitors / pharmacology*
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Reverse Transcriptase Inhibitors / therapeutic use
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Sex Factors
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Time Factors
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Alkynes
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Anti-HIV Agents
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Benzoxazines
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Cholesterol, HDL
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Cyclopropanes
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Reverse Transcriptase Inhibitors
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Aryl Hydrocarbon Hydroxylases
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CYP2B6 protein, human
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Cytochrome P-450 CYP2B6
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Oxidoreductases, N-Demethylating
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efavirenz