CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population. (April 2016)

• Record Type: Journal Article
• Authors: Mukonzo, Jackson K; Bisaso, Ronald K; Ogwal-Okeng, Jasper; Gustafsson, Lars L; Owen, Joel S; Aklillu, Eleni
• Is Part Of: Pharmacogenomics. Volume 17:Number 6(2016)
• Page Start: 603
• Page End: 613
• Publication Date: 2016-04
• Subjects: African population -- cotreatment -- dose recommendations -- efavirenz -- HIV-TB; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.16.7
• Languages: English
• ISSNs: 1462-2416

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.