title: Effect of rifampicin and CYP2B6 genotype on long-term efavirenz autoinduction and plasma exposure in HIV patients with or without tuberculosis.
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.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Ngaimisi
authors.forename: S
authors.initials: S
authors.lastname: Mugusi
authors.forename: O
authors.initials: O
authors.lastname: Minzi
authors.forename: P
authors.initials: P
authors.lastname: Sasi
authors.forename: K-D
authors.initials: KD
authors.lastname: Riedel
authors.forename: A
authors.initials: A
authors.lastname: Suda
authors.forename: N
authors.initials: N
authors.lastname: Ueda
authors.forename: M
authors.initials: M
authors.lastname: Janabi
authors.forename: F
authors.initials: F
authors.lastname: Mugusi
authors.forename: W E
authors.initials: WE
authors.lastname: Haefeli
authors.forename: L
authors.initials: L
authors.lastname: Bertilsson
authors.forename: J
authors.initials: J
authors.lastname: Burhenne
authors.forename: E
authors.initials: E
authors.lastname: Aklillu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000480:Alkynes; D000483:Alleles; D019380:Anti-HIV Agents / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000097:blood / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D004347:Drug Interactions; D004790:Enzyme Induction; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018894:Reverse Transcriptase Inhibitors / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use; D012293:Rifampin / Q000097:blood / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; C510164:CYP3A5 protein, human; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz; D012293:Rifampin