title: CYP2B6 genotype, but not rifampicin-based anti-TB cotreatments, explains variability in long-term efavirenz plasma exposure.
abstract: OBJECTIVE
  We investigated the effects of rifampicin-based anti-TB treatment on plasma efavirenz exposure and the implications of CYP2B6 genotype.
  
  
  METHODS
  Antiretroviral therapy-naive Ugandan HIV patients without (n = 157) or with TB coinfection (n = 106) were enrolled and treated with efavirenz-based highly active antiretroviral therapy alone or with rifampicin-based anti-TB therapy, respectively. Efavirenz plasma concentration was determined on day 3 and weeks 1, 2, 8, 12, 16, 20, 24, 28 and 32.
  
  
  RESULTS
  Rifampicin-based anti-TB cotreatment reduced plasma efavirenz exposure during the first 2 weeks (p < 0.05), but no significant effect was observed afterwards. Although not significant, rifampicin-based anti-TB cotreatment inconsistently increased efavirenz exposure over time, which was reduced immediately after completing anti-TB therapy. CYP2B6*6, *11 and ABCB1 c.4036A>G genotypes were significant predictors of efavirenz plasma exposure.
  
  
  CONCLUSIONS
  Plasma efavirenz exposure is mainly influenced by CYP2B6 genotype, but not by rifampicin cotreatment. Therefore, no efavirenz dosage adjustment during rifampicin cotreatment is required in Ugandans.
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, C-168 SE-141 86 Stockholm, Sweden.
authors.forename: Jackson K
authors.initials: JK
authors.lastname: Mukonzo
authors.forename: Sarah
authors.initials: S
authors.lastname: Nanzigu
authors.forename: Paul
authors.initials: P
authors.lastname: Waako
authors.forename: Jasper
authors.initials: J
authors.lastname: Ogwal-Okeng
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafson
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000097:blood / Q000627:therapeutic use*; D060085:Coinfection / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use*; D014376:Tuberculosis / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz; D012293:Rifampin
keywords: ABCB1; CYP2B6; HIV; Ugandans; efavirenz; induction; inhibition; isoniazid; pharmacokinetics; rifampicin