ADME pathway approach for pharmacogenetic studies of anti-HIV therapy

Abstract

Pharmacogenetics holds promise in HIV treatment because of the complexity and potential toxicity of multidrug therapies that are prescribed for long periods. However, there has been limited success with the current approach where one or few candidate genes are examined for a limited number of allelic variants. A change in paradigm emerges from the availability of the HapMap, the wealth of data on less common genetic polymorphisms, and new genotyping technology. We present a comprehensive review of functional and putative functional variants in genes encoding absorption, distribution, metabolism and excretion (ADME) proteins relevant to HIV therapy. We propose an analytical array based on our review of the literature, web resources and use of bioinformatic analysis. We identified 126 genes with proven or potential role in HIV therapy. Variation in these genes can be characterized by 2428 SNPs (in Caucasians). On average, a gene is covered by 20 SNPs. This review compiles information for future analysis of the role of specific genes/variants in the exposure and response to antiretroviral therapy to generate a ranked list of new genetic variants for future studies.