Sequence clusters in human immunodeficiency virus type 1 reverse transcriptase are associated with subsequent virological response to antiretroviral therapy.

Sequence clusters in human immunodeficiency virus type 1 reverse transcriptase are associated with subsequent virological response to antiretroviral therapy.
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人类免疫缺陷病毒 1 型逆转录酶中的序列簇与随后抗逆转录病毒治疗的病毒学反应相关。

DOI:
10.1086/315017
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发表时间:
1999
期刊:
The Journal of infectious diseases.
影响因子:
--
通讯作者:
Richman,DD
Richman,DD
中科院分区:
--
文献类型:
--
作者:
Brown,AJ;Gunthard,HF;Wong,JK;D'Aquila,RT;Johnson,VA;Kuritzkes,DR;Richman,DD

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逆转录酶(RT)中的许多氨基酸(AA)与对核苷(NRTI)和非核苷类抗逆转录病毒药物的耐药有关。它们之间的相互作用对联合治疗的反应仍然知之甚少。在一项试验(ACTG 241)中,在核苷治疗患者中,齐多夫定/二磷酸核苷(DDI)与齐多夫定/DDI/奈韦拉平比较,来自RT编码区的基线序列数据来自55个个体。使用简约方法对序列进行聚类,并在8周和48周分析每个聚类的病毒学应答(基线病毒载量与治疗后病毒载量的比率)。在这两个时间点,AA215的基因簇和基因都与病毒学应答显著相关,而病毒载量与序列簇显示出更强的相关性。序列簇确定了一组患者,他们从未对NRTIs产生高水平耐药性,尽管以前曾接触过核苷,对病毒复制的抑制很差。
Many amino acid (aa) sites in reverse transcriptase (RT) have been implicated in resistance to nucleoside (NRTI) and nonnucleoside antiretrovirals. Interactions between these in response to combination therapy remain poorly understood. In a trial (ACTG 241) of zidovudine/didanosine (ddI) versus zidovudine/ddI/nevirapine in nucleoside-experienced patients, baseline sequence data from the RT coding region was analyzed from 55 individuals. Sequences were clustered by use of a parsimony method and the virological responses (ratio of baseline viral load to viral load after of therapy) for each cluster were analyzed at week 8 and week 48. Both clusters and genotype at aa 215 were significantly associated with virological response at both time points, whereas viral load showed a stronger association with sequence clusters. Sequence clusters identified one group of patients who never developed high-level resistance to NRTIs despite prior nucleoside exposure and poor suppression of viral replication.
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发表时间: 1999
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