title: CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population.
abstract: OBJECTIVE
  To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment outcomes and provide genotype-based EFV doses recommendations during for tuberculosis (TB)-HIV-1 cotreatment.
  
  
  METHODS
  EFV concentrations from 158 HIV-TB co-infected patients treated with EFV/lamivudine/zidovidine and rifampicin were analyzed. Genotype and CD4 and viral load data were analyzed using a population PK model.
  
  
  RESULTS
  Simulated AUCs for 600 mg EFV dose were 1.2- and 2.4-times greater than the product label for Ugandans in general and CYP2B6*6/*6 genotypes respectively. EFV daily doses of 450 and 250 mg for Ugandans and CYP2B6*6/*6 genotypes, respectively, yielded simulated exposures comparable to the product label.
  
  
  CONCLUSIONS
  Around 450 and 250 mg daily doses might meet EFV dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6/*6 genotypes, respectively.
authors.affiliation: Department of Pharmacology & Therapeutics, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
authors.forename: Jackson K
authors.initials: JK
authors.lastname: Mukonzo
authors.affiliation: Department of Pharmacology & Therapeutics, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Bisaso
authors.affiliation: Department of Pharmacology & Therapeutics, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
authors.forename: Jasper
authors.initials: J
authors.lastname: Ogwal-Okeng
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, Karolinska Institutet, SE - 141 86 Stockholm, Sweden.
authors.forename: Lars L
authors.initials: LL
authors.lastname: Gustafsson
authors.affiliation: School of Pharmacy, Union University, 1050 Union University Drive, Jackson, TN 38305, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Owen
authors.affiliation: Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, Karolinska Institutet, SE - 141 86 Stockholm, Sweden.
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara; D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000995:Antitubercular Agents / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage*; D060085:Coinfection / Q000188:drug therapy; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D012293:Rifampin / Q000008:administration & dosage*; D014376:Tuberculosis / Q000188:drug therapy*; D019562:Viral Load / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; C098320:efavirenz; D012293:Rifampin
keywords: African population; HIV-TB; cotreatment; dose recommendations; efavirenz