Surveillance of HIV-1 transmitted integrase strand transfer inhibitor resistance in the UK.

Surveillance of HIV-1 transmitted integrase strand transfer inhibitor resistance in the UK.
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DOI:
10.1093/jac/dkaa309
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发表时间:
2020-11-01
期刊:
The Journal of antimicrobial chemotherapy
影响因子:
--
通讯作者:
Geretti AM
Geretti AM
中科院分区:
其他
文献类型:
--
作者:
Mbisa JL;Ledesma J;Kirwan P;Bibby DF;Manso C;Skingsley A;Murphy G;Brown A;Dunn DT;Delpech V;Geretti AM

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艾滋病毒治疗指南传统上建议在开始抗逆转录病毒治疗之前对所有艾滋病毒阳性个人进行抗药性证据测试。对逆转录酶抑制剂和PI的耐药性测试在常规护理中得到了很好的证实。然而,对整合酶链转移抑制物(INSTI)耐药性的测试不太一致。通过确定全国新近感染人群中Insti耐药性的流行率,为治疗指南提供信息。最近(在4个 月内)艾滋病毒-1感染是使用英国新诊断的艾滋病毒-1感染测试算法确定的。通过超深测序检测整合酶、蛋白酶和逆转录酶中的耐药相关突变(RAM),从而能够灵敏地估计样本中每个耐药变异体的频率。该分析包括在2014年至2016年期间随机选择的655名被确定为最近感染的个人(中位年龄33岁,男性,83% =  ,78%白人)。这些样本分别来自2014年、2015年和2016年的320、138和197个样本。所有样本中没有一例出现高变异频率(≥为20%)的主要INSTI RAM。一个亚组(25/640,3.9%)的主要Insti Ram仅作为低频变异出现(2%-20%)。相反,47/588(8.0%)存在主要的逆转录酶抑制物和高频PI-RAMS。在2014至2016年间,主要的Insti Ram在最近感染HIV-1的成年人中并不常见,只作为临床意义值得怀疑的低频变异出现。建议对新诊断的患者继续监测传播的INSTI耐药证据,以便为临床实践提供信息。
HIV treatment guidelines have traditionally recommended that all HIV-positive individuals are tested for evidence of drug resistance prior to starting ART. Testing for resistance to reverse transcriptase inhibitors and PIs is well established in routine care. However, testing for integrase strand transfer inhibitor (InSTI) resistance is less consistent. To inform treatment guidelines by determining the prevalence of InSTI resistance in a national cohort of recently infected individuals. Recent (within 4 months) HIV-1 infections were identified using a Recent Infection Testing Algorithm of new HIV-1 diagnoses in the UK. Resistance-associated mutations (RAMs) in integrase, protease and reverse transcriptase were detected by ultradeep sequencing, which allows for the sensitive estimation of the frequency of each resistant variant in a sample. The analysis included 655 randomly selected individuals (median age = 33 years, 95% male, 83% MSM, 78% white) sampled in the period 2014 to 2016 and determined to have a recent infection. These comprised 320, 138 and 197 samples from 2014, 2015 and 2016, respectively. None of the samples had major InSTI RAMs occurring at high variant frequency (≥20%). A subset (25/640, 3.9%) had major InSTI RAMs occurring only as low-frequency variants (2%–20%). In contrast, 47/588 (8.0%) had major reverse transcriptase inhibitor and PI RAMs at high frequency. Between 2014 and 2016, major InSTI RAMs were uncommon in adults with recent HIV-1 infection, only occurring as low-frequency variants of doubtful clinical significance. Continued surveillance of newly diagnosed patients for evidence of transmitted InSTI resistance is recommended to inform clinical practice.
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期刊: PloS one
影响因子: 3.7
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