The impact of host pharmacogenetics on antiretroviral drug disposition.
The ability to predict efficacy and toxicity during antiretroviral therapy for HIV would be of obvious advantage. The substantial variability between patients in terms of bioavailability and distribution of current regimens is likely driven by genetic and environmental factors. Protease inhibitors and nucleoside/nucleotide reverse transcriptase inhibitors are metabolized by cytochrome P450 enzymes. Their bioavailability and excretion may also be affected by variability in drug transporters of the ABC and SLC families. In pharmacokinetics and efficacy studies, issues are complicated by multiple loci effects (driven by the large number of proteins contributing to disposition) and heterogeneity in both study populations and the virus (ie, the target). Some of these issues are now being tackled, but studies need to be sufficiently powered and the phenotype carefully characterized. This review aims to summarize the current understanding of pharmacogenetic determinants of antiretroviral disposition.
Owen
Andrew
A
Department of Pharmacology and Therapeutics, University of Liverpool, 70 Pembroke Place, Liverpool L69 3GF, UK. aowen@liverpool.ac.uk