感染艾滋病毒的孕妇体内与整合酶链转移抑制剂耐药性相关的突变。

D Cecchini, J Sfalcin, I Zapiola, A Gomez, S Fernandez-Giuliano, C Rodriguez, L Mammana, A Seravalle, F Fay, M C Torroija, G Bugarín, M B Bouzas
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引用次数: 0

摘要

目的:迄今为止,还没有关于拉丁美洲感染艾滋病毒的孕妇(HPW)中整合酶抑制剂(INSTI)耐药性相关突变(HIVDRM)流行率的数据。我们利用新一代测序技术(NGS)描述了阿根廷 INSTI 耐药 HPW 历史队列(n=56)中整合酶 HIVDRM 的流行率和传播性:使用 HyDRA 软件对 20%、10%、5%、2% 和 1% 的敏感性阈值进行生物信息学分析。我们计算了每种 INSTI-HIVDRM 的突变病毒载量,将大于 1000 c/mL 的病毒视为高传播风险病毒:主要的 HIV 亚型是 BF(78.5%)。使用人群测序 20% 过滤器未检测到主要的 HIVDRM。以 1%为阈值,发病率增至 8.9%;发现了 Y143C/S、E92G、E138K 和 T66I 突变。突变负荷(以 c/mL 表示)的中位数(范围)为辅助突变(G163R/K、T97A)的检测灵敏度阈值大多为 20%,总发生率为 23.2%;突变负荷中位数(IQR)为:23929 (4009-63158) c/mL;所有突变负荷均高于 1000 c/mL:我们的研究结果表明,在 HPW 中存在主要的 INSTI-HIVDRM 变异和高频率的具有潜在传播性的附属变异。
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Integrase strand transfer inhibitors resistance-associated mutations in HIV-infected pregnant women.

Objective: To date, no data exist regarding the prevalence of integrase inhibitor (INSTI) resistance-associated mutations (HIVDRM) in HIV-infected pregnant women (HPW) in Latin America. We describe the prevalence and transmissibility of integrase HIVDRM in a historical cohort of INSTI-naïve HPW from Argentina (n=56) with Next Generation Sequencing (NGS).

Methods: Bioinformatics analysis was performed by HyDRA software for 20%, 10%, 5%, 2%, and 1% sensitivity thresholds. We calculated the mutational viral load for each INSTI-HIVDRM, considering those with >1000 c/mL as of high risk of transmissibility.

Results: The predominant HIV subtype was BF (78.5%). Major HIVDRM were not detected with the population sequencing 20% filter. With a 1% threshold, the prevalence increased to 8.9%; Y143C/S, E92G, E138K, and T66I mutations were found. The median (range) mutational load (expressed in c/mL) was: 355 (50.2-11705); with only 1 case >1000 c/mL Accessory mutations (G163R/K, T97A) were detected mostly with a 20% sensitivity threshold with an overall prevalence of 23.2%; the median (IQR) mutational load was: 23929 (4009-63158) c/mL; all of them above 1000 c/mL.

Conclusions: Our results show evidence of the presence of major INSTI-HIVDRM as aleatory mutations and a high frequency of accessory mutations with potential transmissibility in HPW.

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