Abstract
We performed a prospective comparative study to examine, from a pharmacogenetics perspective, the effect of rifampicin (RIF) on long-term efavirenz (EFV) autoinduction and kinetics. In a study population of patients with HIV receiving EFV with RIF (arm 2, n = 54) or without RIF (arm 1, n = 128 controls), intraindividual and interindividual plasma EFV and 8-hydroxyefavirenz levels were compared at weeks 4 and 16 of EFV therapy. In arm 2, RIF was initiated 4 weeks before starting EFV. In controls (arm 1), the plasma EFV was significantly lower whereas 8-hydroxyefavirenz was higher at week 16 as compared to week 4. By contrast, there were no significant differences in plasma EFV and 8-hydroxyefavirenz concentrations over time in arm 2. At week 4, the plasma EFV concentration was significantly lower in arm 2 as compared to arm 1, but no significant differences were observed by week 16. When stratified by CYP2B6 genotype, significant differences were observed only with respect to CYP2B6*1/*1 genotypes. Ours is the first report of the CYP2B6 genotype-dependent effect of RIF on long-term EFV autoinduction.
Publication types
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Comparative Study
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Controlled Clinical Trial
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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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Alkynes
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Alleles
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Anti-HIV Agents / blood
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Anti-HIV Agents / metabolism
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Anti-HIV Agents / therapeutic use
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Antibiotics, Antitubercular / blood
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Antibiotics, Antitubercular / therapeutic use*
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Antiretroviral Therapy, Highly Active
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Aryl Hydrocarbon Hydroxylases / genetics*
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Benzoxazines / blood*
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Benzoxazines / metabolism
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Benzoxazines / therapeutic use
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Cyclopropanes
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Cytochrome P-450 CYP2B6
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Cytochrome P-450 CYP3A / genetics
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Drug Interactions
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Enzyme Induction
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Female
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Genotype
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HIV Infections / drug therapy
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HIV Infections / genetics
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HIV-1 / drug effects
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HIV-1 / genetics
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Humans
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Male
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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 / metabolism
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Reverse Transcriptase Inhibitors / therapeutic use
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Rifampin / blood
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Rifampin / therapeutic use*
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Tuberculosis / drug therapy
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Tuberculosis / genetics
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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Antibiotics, Antitubercular
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Benzoxazines
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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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CYP3A5 protein, human
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Cytochrome P-450 CYP2B6
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Cytochrome P-450 CYP3A
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Oxidoreductases, N-Demethylating
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efavirenz
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Rifampin