How recent findings on the pharmacokinetics and pharmacodynamics of integrase inhibitors can inform clinical use.

Elliot, Emilie, Chirwa, Mimie and Boffito, Marta (2017) How recent findings on the pharmacokinetics and pharmacodynamics of integrase inhibitors can inform clinical use. Current opinion in infectious diseases, 30 (1). pp. 58-73.

Text How recent findings on the pharmacokinetics and pharmacodynamics of integrase inhibitors can inform clinical use_final version post review.docx - Author Accepted Manuscript Download (120kB)

Abstract

<h4>Purpose of review</h4>This review of recent published literature and data presented at scientific meetings on integrase stand transfer inhibitors (InSTIs) examines how these findings may impact on their future clinical use.<h4>Recent findings</h4>Elvitegravir (EVG), raltegravir (RAL) and dolutegravir (DTG) are InSTIs recommended as first-line options for treatment naive patients by the European AIDS Clinical Society, British HIV Association, International AIDS Society-USA and DHHS. InSTIs have gained a leading role in the management of HIV-1 because of increased viral suppression and maintaining undetectability with fewer side-effects.RAL 1200 mg once-daily (QD) has been shown to be noninferior to 400 mg BD, and the European Medicines Agency has approved QD RAL for review. RAL and DTG are not metabolized via cytochrome P450 (CYP) resulting in fewer drug interactions and less toxicity risk in patients receiving direct-acting antivirals and other coadministered medications.EVG is currently available as a single tablet regimen and requires cobisistat, a pharmacokinetic booster and CYP3A inhibitor to allow QD dosing. EVG will soon be available in combination with tenofovir alfenamide, which is as efficacious as tenofovir disoproxil fumarate, but offers better renal and bone outcomes.DTG has a high genetic barrier to resistance and has been the subject of a number of simplification and treatment failure trials and shown promise. There are some emerging reports of neuropsychiatric and gastrointestinal side-effects associated with DTG, which were not reported in clinical trials emphasizing the importance of real-life data.Carbotegravir, a long-acting InSTI, is currently in the pipeline of development.<h4>Summary</h4>All three InSTIs have impressive data on efficacy, tolerability and safety. The unique differences of each InSTI's pharmacokinetics and pharmacodynamics lend themselves to various clinical scenarios, enabling us as clinicians to provide better patient-centred care.

Item Type:	Article
Uncontrolled Keywords:	Humans, HIV-1, HIV Infections, Oxazines, Piperazines, Pyridones, Quinolones, Heterocyclic Compounds, 3-Ring, HIV Integrase Inhibitors, Viral Load, Drug Interactions, Raltegravir Potassium, Cobicistat
Depositing User:	Symplectic Admin
Date Deposited:	05 Mar 2020 15:14
Last Modified:	19 Jan 2023 00:00
DOI:	10.1097/qco.0000000000000327
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3076611