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20 - Pharmaco-genomics of antiretroviral drugs

from Part IV - Next-generation sequencing technology and pharmaco-genomics

Published online by Cambridge University Press:  18 December 2015

By
Chonlaphat Sukasem ,
Apichaya Puangpetch  and
Sadeep Medhasi
Edited by
Krishnarao Appasani
Foreword by
Stephen W. Scherer  and
Peter M. Visscher
Chonlaphat Sukasem
Affiliation:
Mahidol University Faculty of Medicine
Apichaya Puangpetch
Affiliation:
Mahidol University Faculty of Medicine
Sadeep Medhasi
Affiliation:
Mahidol University Faculty of Medicine
Krishnarao Appasani
Affiliation:
GeneExpression Systems, Inc., Massachusetts
Stephen W. Scherer
Affiliation:
University of Toronto
Peter M. Visscher
Affiliation:
University of Queensland
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Summary

Introduction

Currently several million people take chronic combination antiretroviral (ARV) therapy to suppress human immunodeficiency virus (HIV) infection. There are around 34 million people living with the HIV infection, most of whom reside in developing or under-developed nations. The combined antiretroviral therapy (cART) has prolonged life and prevented the progression of the disease. The cART has lessened the burden of the disease worldwide (Verma et al., 2014). Because of the long-term and multi-drug therapy, several complexities may arise which might affect adherence and tolerability in patients. Serious efforts must be made in order to make the pharmacotherapy of HIV infection efficacious with minimal adverse events. The use of ARV drugs has been associated with different types of toxicities including hypersensitivity reactions, metabolic disturbances, peripheral neuropathy, hyperbilirubinemia, neuropsychiatry disorders, and myelosupression (Subbaraman et al., 2007). Among several variables, such as age, sex, disease state, and drug–drug interactions influencing inter-patient variability in the spectrum of effectiveness and toxic effects of ARV drugs, host genetic factors may have a significant role in predisposing the patient to the variation in treatment outcome (Vidal et al., 2010). Polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and other targets make the patient susceptible to variation in drug response. It is imperative to predict the genetic markers to optimize the therapy and select the best combination of drugs to avoid toxicity. The application of pharmacogenomics in clinical practice might help us to develop the notion of personalized medicine. Pharmacogenetic tests can provide the data on genetically determined inter-individual differences in pharmacokinetics and genotype–phenotype associations (Shah and Shah, 2012).

This chapter reviews the pharmaco-genetic aspects of variation in ARV drug response in HIV-infected patients. The most overlapping examples of the heterogeneity in the efficacy and toxic effects of ARV drugs as found between populations will be discussed here.

Antiretroviral drugs

ARV drugs are commonly used to prevent transmission or acquisition of HIV-1 infection. Current practice uses a combination of at least three drugs referred to as “highly active antiretroviral therapy” (HAART) in the standard-of-care therapy for HIV infection. Zidovudine was the first drug to be approved by Food and Drug Administration (FDA) to treat HIV infection in 1987. There has been remarkable improvement in the prognosis of HIV infection since 1995 with the use of HAART (Pirmohamed and Back, 2001).

Type
Chapter
Information
Genome-Wide Association Studies
From Polymorphism to Personalized Medicine
 , pp. 297 - 312
Publisher: Cambridge University Press
Print publication year: 2016

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