1. CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population.
- Author
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Mukonzo JK, Bisaso RK, Ogwal-Okeng J, Gustafsson LL, Owen JS, and Aklillu E
- Subjects
- Adult, Africa South of the Sahara, Alkynes, Anti-HIV Agents administration & dosage, Coinfection drug therapy, Cyclopropanes, Female, Genotype, HIV-1 drug effects, Humans, Lamivudine administration & dosage, Male, Viral Load drug effects, Zidovudine administration & dosage, Antitubercular Agents administration & dosage, Benzoxazines administration & dosage, Cytochrome P-450 CYP2B6 genetics, HIV Infections drug therapy, Reverse Transcriptase Inhibitors administration & dosage, Rifampin administration & dosage, Tuberculosis drug therapy
- Abstract
Aim: To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment outcomes and provide genotype-based EFV doses recommendations during for tuberculosis (TB)-HIV-1 cotreatment., Materials & 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.
- Published
- 2016
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