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Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs

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Abstract

Background

Antiretroviral treatment is highly effective in enhancing HIV-positive patients' survival and quality of life. Despite an increased tolerability in recent years, a substantial amount of patients experience side effects. Antiretrovirals' efficacy and tolerability have been associated with plasma concentrations and single nucleotide polymorphisms in selected genes involved in drug disposition.

Objective

Our aim was to review the current knowledge in genetic polymorphisms affecting plasma, intracellular or compartmental concentrations of antiretrovirals.

Methods

A search of the PubMed database was conducted to identify relevant articles, using the following terms: ‘pharmacogenetics’ or ‘pharmacogenomics’ or ‘single nucleotide polymorphisms’ or ‘genetic/allelic variants’ and ‘pharmacokinetics’ or ‘concentrations’ and ‘HIV’ or ‘antiretroviral’. Abstracts from the main HIV conferences during 2015 and 2016 were also searched using the same keywords. Abstracts were manually checked and, if relevant, full papers were obtained. Only articles published in English were selected.

Results

Several genetic polymorphisms in genes coding enzymes involved in drug metabolism (cytochrome P450 isoenzymes and uridine diphosphate glucuronosyltransferases) and transport (P-glycoprotein, anionic and cationic transporters, other transporters), as well as nuclear receptors (pregnane X receptor and the constitutive androstane receptor), have been associated with concentrations of antiretrovirals. The extent of such influence, the conflicting data, and the potential clinical relevance are discussed in the main section of this article.

Conclusion

Genetic polymorphisms may affect antiretroviral disposition, as well as both efficacy and toxicity. Despite a large amount of data, such precious knowledge has seldom been applied in patients. Studies on the clinical relevance and cost effectiveness of tailoring antiretroviral regimens to patients’ genetic assets are lacking, but their importance may grow with the increasing age and complexity of persons living with HIV/AIDS.

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Authors and Affiliations

  1. Unit of Infectious Diseases, Department of Medical Sciences, University of Torino, c/o Ospedale Amedeo di Savoia, C.so Svizzera 164, 10159, Torino, Italy

    Andrea Calcagno, Jessica Cusato, Antonio D’Avolio & Stefano Bonora

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  1. Andrea Calcagno
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  2. Jessica Cusato
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Correspondence to Andrea Calcagno.

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Andrea Calcagno has received travel grants or speaker’s honoraria from Abbott, Bristol–Myers Squibb (BMS), Merck Sharp & Dohme (MSD) and Janssen-Cilag. Stefano Bonora has received grants, travel grants and consultancy fees from Abbott, Boehringer–Inghelheim, BMS, Gilead-Sciences, GlaxoSmithKline, MSD, Pfizer and Janssen-Cilag. Jessica Cusato and Antonio D’Avolio have no conflicts of interest to declare.

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Calcagno, A., Cusato, J., D’Avolio, A. et al. Genetic Polymorphisms Affecting the Pharmacokinetics of Antiretroviral Drugs. Clin Pharmacokinet 56, 355–369 (2017). https://doi.org/10.1007/s40262-016-0456-6

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