体内多种突变的积累赋予了对新型和现有整合酶抑制剂的交叉耐药性。
Accumulation of Multiple Mutations In Vivo Confers Cross-Resistance to New and Existing Integrase Inhibitors.
机构信息
University of British Columbia, Vancouver, Canada.
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
出版信息
J Infect Dis. 2018 Oct 20;218(11):1773-1776. doi: 10.1093/infdis/jiy428.
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).
比替格瑞韦（BIC）和卡替拉韦（CAB）是临床试验中最新的可用的 HIV 整合酶抑制剂。主要整合酶抑制剂取代 G140S/Q148H 的组合已被证明对已批准的整合酶抑制剂拉替拉韦（RAL）和艾维雷韦（EVG）具有高度耐药性，但不一定对多替拉韦（DTG）具有耐药性。我们对来自患者衍生 RNA 提取物的重组病毒进行了抗药性表型检测，这些病毒包含了具有附加辅助取代的 G140S/Q148H。多种整合酶取代的积累赋予了对所有 5 种整合酶抑制剂的高度耐药性。DTG、BIC 和 CAB 之间存在广泛的交叉耐药性（r = 0.96-0.97）。
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