Host determinants of antiretroviral drug activity

Abstract

As physicians are confronted with a diversity of adverse events and variability in response to medication among patients, this review will focus on the available evidence regarding the impact of genetic variation on drug response. Specifically, variation in drug metabolizing enzymes such as the cytochrome P450s, drug transporters and human leucocyte antigen (for idiosyncratic drug reactions). The potential role of pharmacogenetics in the management of HIV-1 infected individuals and drug discovery will be discussed. Wide inter-individual variability of antiretroviral therapy efficacy and toxicity in HIV-infected patients has been extensively reported in the literature. Since treatment involves multiple drugs and drug classes with the potential for significant variability in drug-host as well as drug-drug interactions, antiretroviral drug therapy represents a significant challenge. Despite this inherent complexity, considerable recent advances have led to a greater understanding of interactions between genetic and host factors that influence the efficacy and toxicity of these agents. The goal of pharmacogenetics in antiretroviral therapy is to outline differences within a given population that influence drug efficacy and toxicity. Although to date, despite the numerous studies available in the literature, conclusions on how the analysis of the relationship between single nucleotide polymorphisms and drug efficacy may not always be clinically useful. Further studies are warranted to clarify the role of pharmacogenetics and antiretroviral drug management.