Pharmacogenomics and Antiretroviral Therapy: Pharmacogenomics of HIV-1 Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors - Implications for Personalized Antiretroviral Therapy

Recent developments in the pharmacogenomics of antiretroviral therapy have provided new prospects for the prediction of treatment efficacy and adverse effects. Current antiretroviral treatment has limitations such as high rates of adverse drug reactions and the development of resistance in a significant proportion of patients. HIV- 1 protease inhibitors and non-nucleoside reverse transcriptase inhibitors are particularly suitable for genomic investigations since drug exposure/concentration and treatment response can be quantified and adverse effects can be assessed with validated measures. Additionally, there is an extensive knowledge of the pharmacokinetics of these agents, and candidate genes implicated in metabolism, transport and adverse effects have been identified. Although no unifying conclusions have been reached regarding the association of genetic variants with pharmacokinetics and adverse drug reactions, this chapter attempts to review the most recently published research and summarize the state of research in this area. Future directions for research in individualizing these agents are discussed.

Keywords: Pharmacogenomics, Personalized ART, Antiretoviral Therapy, Protease Inhibitors, Non-nucleoside Reverse Transcriptase Inhibitors, HLAB* 5701, HIV Genetics, Protease Inhibitors, NNRTI, CYP3A4/5, Hyperbilirubinemia.