Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2024-01-01 Epub Date: 2024-12-19 DOI:10.1080/14622416.2024.2441104

Lisanne A H Bevers, Rebecca L Jensen, Andrew Owen, Angela Colbers, Daniel F Carr, David M Burger

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引用次数: 0

Abstract

Background: Dolutegravir (DTG) is an antiviral agent used for the treatment of HIV, however, there is uncertainty over the influence of genetic variation on DTG exposure, and whether it has clinical implications for the efficacy or toxicity in different populations. This systematic review aims to create an overview of the impact of pharmacogenomics (PGx) on DTG exposure, efficacy, and toxicity.

Methods: Publications up to 14 November 2023 were searched and articles were selected on the following criteria: original research articles providing data on people with HIV, data on PGx and either PK or PD or both PD and PGx.

Results: 711 records were identified, and after screening 10 articles were included. Commonly analyzed genes across the articles were UGT1A1, ABCB1, ABCG2, and NR1I2. The most reported variant associated with PD variability was in SLC22A2, with carriers at higher risk of neuropsychiatric adverse events.

Conclusions: This review concludes that while PGx testing may help explain some variability in DTG pharmacokinetics when combined with therapeutic drug monitoring (TDM), current evidence is insufficient to support its routine clinical use. The role of PGx research for DTG remains relevant, especially in specific patient populations where interindividual PK variations are still unexplained.

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多替格拉韦药代动力学的遗传变异及其与安全性和有效性结果的关系：系统综述。

背景：多替格拉韦（Dolutegravir， DTG）是一种用于治疗HIV的抗病毒药物，然而，遗传变异对多替格拉韦暴露的影响，以及它在不同人群中是否具有疗效或毒性的临床意义尚不确定。本系统综述旨在概述药物基因组学（PGx）对DTG暴露、疗效和毒性的影响。方法：检索截至2023年11月14日的出版物，并根据以下标准选择文章：提供HIV患者数据的原创研究文章，PGx和PK或PD的数据或PD和PGx的数据。结果：共纳入711篇文献，经筛选纳入10篇文献。文章中常见的分析基因为UGT1A1、ABCB1、ABCG2和NR1I2。与PD变异性相关的变异最多的是SLC22A2，其携带者有较高的神经精神不良事件风险。结论：本综述得出结论，虽然PGx检测可能有助于解释与治疗药物监测（TDM）联合使用时DTG药代动力学的一些变异性，但目前的证据不足以支持其常规临床应用。PGx研究在DTG中的作用仍然是相关的，特别是在个体间PK变化仍然无法解释的特定患者群体中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.