Jackson K Mukonzo1, Ronald K Bisaso1, Jasper Ogwal-Okeng1, Lars L Gustafsson2, Joel S Owen3, Eleni Aklillu2. 1. Department of Pharmacology & Therapeutics, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda. 2. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital-Huddinge, Karolinska Institutet, SE - 141 86 Stockholm, Sweden. 3. School of Pharmacy, Union University, 1050 Union University Drive, Jackson, TN 38305, USA.
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.
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-infectedpatients 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: Immaculate M Langmia; Katja S Just; Sabrina Yamoune; Jürgen Brockmöller; Collen Masimirembwa; Julia C Stingl Journal: Front Genet Date: 2021-07-12 Impact factor: 4.599