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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 1/2017

01-01-2017 | Review Article

Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors

Authors: Anthony T. Podany, Kimberly K. Scarsi, Courtney V. Fletcher

Published in: Clinical Pharmacokinetics | Issue 1/2017

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Abstract

Dolutegravir (DTG), elvitegravir (EVG) and raltegravir (RAL) are members of the latest class of antiretrovirals (ARVs) that have become available to treat human immunodeficiency virus (HIV) infection: integrase strand transfer inhibitors (INSTIs). INSTIs are potent inhibitors of the HIV integrase enzyme, with protein binding–adjusted concentration inhibiting viral replication by 90/95 % [IC90/95] values in the low nanogram per millilitre range, and they retain antiviral activity against strains of HIV with acquired resistance to other classes of ARVs. Each of the INSTIs has unique pharmacokinetic/pharmacodynamic properties, influencing its role in clinical use in specific subsets of patients. RAL and DTG have minimal drug–drug interaction profiles, as their metabolism has minimal cytochrome P450 (CYP) involvement. Conversely, EVG metabolism occurs primarily via CYP3A4 and requires pharmacokinetic boosting to achieve systemic exposures amenable to once-daily dosing. EVG and DTG have the added benefit of availability of fixed-dose combination tablets, allowing for convenient and simplified ARV regimens. RAL is the only INSTI to be listed as a preferred agent in the current US perinatal treatment guidelines. All three INSTIs are recommended regimens for treatment-naïve individuals in the US adult and adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the INSTIs, and describes specific pharmacokinetic considerations for special patient conditions: hepatic impairment, renal dysfunction, pregnancy and co-infections.
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Metadata
Title
Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors
Authors
Anthony T. Podany
Kimberly K. Scarsi
Courtney V. Fletcher
Publication date
01-01-2017
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 1/2017
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-016-0424-1

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