Optimization of Efavirenz Dosing During Treatment of HIV-1 Infected Adults in an African Population
by Open Science Repository Pharmaceutics
Efavirenz is the currently recommended first choice NNRTI for HIV patients receiving rifampicin TB co-treatment. While efavirenz exhibits a narrow therapeutic window, with plasma drug > 4 µg/ml and < 1 µg/ml being associated with central nervous system symptoms and increased virological failure respectively, it also exhibits significant inter-individual pharmacokinetic and pharmacodynamic variability.
Africans, a population that is uniquely different in terms of frequency of SNPs relevant for efavirenz pharmacokinetics and treatment outcome is also most affected by both HIV and TB, therefore requiring rifampicin-efavirenz co-treatment. Genes known to predict efavirenz pharmacokinetics include CYP2B6 and ABCB1. Rifampicin is an enzyme inducer for CYP2B6. While CYPB6 SNP frequencies differ greatly for Africans compared to other populations, efavirenz dosing has not been optimized for the population. We aim to use pharmacokinetic-pharmacogenetic–pharmacodynamic modeling in NONMEM to predict efavirenz optimal doses for Uganda patients.Keywords:
efavirenz, dosing, African, HIV patients.
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