Accumulation of Multiple Mutations In Vivo Confers Cross-Resistance to New and Existing Integrase Inhibitors

被引：32

作者：

Zhang, Wendy W. ^{[1
,2
]}

Cheung, Peter K. ^{[2
]}

Oliveira, Natalia ^{[2
]}

Robbins, Marjorie A. ^{[2
,3
]}

Harrigan, P. Richard ^{[1
]}

Shahid, Aniqa ^{[2
]}

机构：

[1] Univ British Columbia, Vancouver, BC, Canada

[2] British Columbia Ctr Excellence HIV AIDS, Vancouver, BC, Canada

[3] BC Childrens Hosp Res Inst, Vancouver, BC, Canada

来源：

JOURNAL OF INFECTIOUS DISEASES | 2018年 / 218卷 / 11期

基金：

加拿大健康研究院;

关键词：

integrase inhibitors; bictegravir; cabotegravir; dolutegravir; integrase resistance testing; phenotype; RALTEGRAVIR; DOLUTEGRAVIR; BICTEGRAVIR;

D O I：

10.1093/infdis/jiy428

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Bictegravir (BIC) and cabotegravir (CAB) are the latest available HIV integrase inhibitors in clinical trials. The combination of major integrase inhibitor substitutions G140S/Q148H has been shown to confer high-level resistance to the approved integrase inhibitors raltegravir (RAL) and elvitegravir (EVG) but not necessarily dolutegravir (DTG). We assayed recombinant viruses made from patient-derived RNA extracts for resistance phenotype for a panel of viruses containing G140S/Q148H with additional accessory substitutions. The accumulation of multiple integrase substitutions confers high-level resistance to all 5 integrase inhibitors. There is extensive cross-resistance between DTG, BIC, and CAB (r = 0.96-0.97).

引用

页码：1773 / 1776

页数：4

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