Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
Transmitted HIV-1 drug resistance in a large international cohort using next-generation sequencing: results from the Strategic Timing of Antiretroviral Treatment (START) study.
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DOI：
10.1111/hiv.13038
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发表时间：
2021-05
期刊：
影响因子：
3
通讯作者：
INSIGHT START Study Group
中科院分区：
文献类型：
--
作者：
Baxter JD;Dunn D;Tostevin A;Marvig RL;Bennedbaek M;Cozzi-Lepri A;Sharma S;Kozal MJ;Gompels M;Pinto AN;Lundgren J;INSIGHT START Study Group
本分析的目的是通过下一代测序（NGS）（一种能够检测低频变异的敏感检测方法）来表征抗逆转录病毒治疗战略时机（START）研究参与者中的传播性耐药（TDR）。NGS（Illumina MiSeq）分析了输入HIV RNA > 1000拷贝/mL的参与者的储存血浆。TDR基于WHO 2009年监测定义，添加了逆转录酶（RT）突变T215 N和E138 K以及整合酶链转移抑制剂（HIVI）监测突变（斯坦福大学HIVdb）。报告了在三个阈值下检测到的耐药突变（DRM）：> 2%、5%和20%的病毒群体。2009年至2013年间，START在35个国家招募了4684名抗逆转录病毒治疗（ART）初治者。2902名参与者在研究入组时的基线NGS数据可用。使用2%/5%/20%的检测阈值，核苷类逆转录酶抑制剂（NRTI）的TDR总体患病率为9.2%/5.6%/3.2%，非NRTI为9.2%/6.6%/4.9%，蛋白酶抑制剂（PI）为11.4%/5.5%/2.4%，CIMI DRM为3.5%/1.6%/0.1%，且因地理区域而异。使用2%的检测阈值，患病率最高的单个DRM是：PI M46 IL（5.5%）、RT K103 NS（3.5%）、RT G190 ASE（3.1%）、T215 ISCDVEN（2.5%）、RT M41 L（2.2%）、RT K219 QENR（1.7%）和PI D30 N（1.6%）。在20%的检测阈值以下，几乎完全检测到了T66 I DRM，最常见的是Y143 H（0.4%）、Q148 R（0.4%）和T66 I（0.4%）。在该研究人群中使用NGS导致检测到大比例的低水平变异，这些变异通过传统桑格测序无法检测到。利用NGS进行的全球监测研究应能对世界不同地区的TDR患病率进行更全面的评估。
The aim of this analysis was to characterize transmitted drug resistance (TDR) in Strategic Timing of Antiretroviral Treatment (START) study participants by next-generation sequencing (NGS), a sensitive assay capable of detecting low-frequency variants. Stored plasma from participants with entry HIV RNA > 1000 copies/mL were analysed by NGS (Illumina MiSeq). TDR was based on the WHO 2009 surveillance definition with the addition of reverse transcriptase (RT) mutations T215N and E138K, and integrase strand transfer inhibitor (INSTI) surveillance mutations (Stanford HIVdb). Drug resistance mutations (DRMs) detected at three thresholds are reported: > 2%, 5% and 20% of the viral population. Between 2009 and 2013, START enrolled 4684 antiretroviral therapy (ART)-naïve individuals in 35 countries. Baseline NGS data at study entry were available for 2902 participants. Overall prevalence rates of TDR using a detection threshold of 2%/5%/20% were 9.2%/5.6%/3.2% for nucleoside reverse transcriptase inhibitors (NRTIs), 9.2%/6.6%/4.9% for non-NRTIs, 11.4%/5.5%/2.4% for protease inhibitors (PIs) and 3.5%/1.6%/0.1% for INSTI DRMs and varied by geographic region. Using the 2% detection threshold, individual DRMs with the highest prevalence were: PI M46IL (5.5%), RT K103NS (3.5%), RT G190ASE (3.1%), T215ISCDVEN (2.5%), RT M41L (2.2%), RT K219QENR (1.7%) and PI D30N (1.6%). INSTI DRMs were detected almost exclusively below the 20% detection threshold, most commonly Y143H (0.4%), Q148R (0.4%) and T66I (0.4%). Use of NGS in this study population resulted in the detection of a large proportion of low-level variants which would not have been detected by traditional Sanger sequencing. Global surveillance studies utilizing NGS should provide a more comprehensive assessment of TDR prevalence in different regions of the world.
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DOI：
10.1093/cid/ciy881
发表时间：
2019-07-02
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Derache A;Iwuji CC;Baisley K;Danaviah S;Marcelin AG;Calvez V;de Oliveira T;Dabis F;Porter K;Pillay D
通讯作者：
Pillay D
DOI：
10.1093/jac/dku426
发表时间：
2015-03
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Cozzi-Lepri A;Noguera-Julian M;Di Giallonardo F;Schuurman R;Däumer M;Aitken S;Ceccherini-Silberstein F;D'Arminio Monforte A;Geretti AM;Booth CL;Kaiser R;Michalik C;Jansen K;Masquelier B;Bellecave P;Kouyos RD;Castro E;Furrer H;Schultze A;Günthard HF;Brun-Vezinet F;Paredes R;Metzner KJ;CHAIN Minority HIV-1 Variants Working Group
通讯作者：
CHAIN Minority HIV-1 Variants Working Group
影响因子：
3.1
作者：
Huber, Michael;Metzner, Karin J.;Zagordi, Osvaldo
通讯作者：
Zagordi, Osvaldo
影响因子：
3.7
作者：
Bennett DE;Camacho RJ;Otelea D;Kuritzkes DR;Fleury H;Kiuchi M;Heneine W;Kantor R;Jordan MR;Schapiro JM;Vandamme AM;Sandstrom P;Boucher CA;van de Vijver D;Rhee SY;Liu TF;Pillay D;Shafer RW
通讯作者：
Shafer RW
影响因子：
3
作者：
Archer J;Baillie G;Watson SJ;Kellam P;Rambaut A;Robertson DL
通讯作者：
Robertson DL