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首页> 外文期刊>AIDS Research and Human Retroviruses >Intrapatient Evolutionary Dynamics of Human Immunodeficiency Virus Type 1 in Individuals Undergoing Alternative Treatment Strategies with Reverse Transcriptase Inhibitors
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Intrapatient Evolutionary Dynamics of Human Immunodeficiency Virus Type 1 in Individuals Undergoing Alternative Treatment Strategies with Reverse Transcriptase Inhibitors

机译：人类免疫缺陷病毒1型患者在接受替代治疗策略与逆转录酶抑制剂的患者中的住院患者进化动力学。

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摘要

Structured treatment interruption (STI) has been trialed as an alternative to lifelong antiretroviral therapy (ART). We retrospectively performed single genome sequencing of the HIV-1 pol region from three patients representing different scenarios. They were either failing on continuous therapy (CT-F), failing STI (STI-F), or suppressing on STI (STI-S). Over 460 genomes were generated from three to five different time points over a 2-year period. We found multiple-linked-resistant mutations in both treatment failures. However, the CT-F patient showed a stepwise accumulation of diverse, linked mutations whereas the STI-F patient had lineage turnover between treatment periods with recirculation of wild-type and resistant variants from reservoirs. The STI-F patient showed a 7-fold increase in the third codon position substitution rate relative to the first and second positions compared to a 2-fold increase for CT-F and increased purifying selection in the pol gene (62 vs. 22 sites, respectively). An understanding of intrapatient viral dynamics could guide the future direction of treatment interruption strategies.
机译：结构性治疗中断（STI）已被试用作为终生抗逆转录病毒治疗（ART）的替代方法。我们回顾性地从代表不同情况的三名患者中对HIV-1 pol区进行了单基因组测序。他们要么连续治疗失败（CT-F），性传播感染失败（STI-F），要么就抑制性传播感染（STI-S）。在两年的时间内，从三个到五个不同的时间点生成了460多个基因组。我们在两种治疗失败中均发现了多重连锁耐药突变。但是，CT-F患者表现出逐步积累的各种相关突变，而STI-F患者在治疗期之间有谱系更新，其中有来自库的野生型和抗性变异株的再循环。 STI-F患者显示第三密码子位置取代率相对于第一和第二位置增加了7倍，而CT-F则增加了2倍，并且pol基因的纯化选择增加了（62位对22位） ， 分别）。对患者体内病毒动力学的了解可以指导治疗中断策略的未来方向。

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