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[2004 - 2008年辽宁省初治艾滋病病毒1型感染者中与原发性耐药相关突变的基因特征]

[Genetic characteristics of HIV-1 primary drug resistance-associated mutations in treatment-naive individuals in Liaoning province, 2004-2008].

作者信息

Wu Shao-hui, Lu Chun-ming, Jiang Feng-xia, E Shuang, Ma Ning, Liang Xue-wei, Gai Xiao-qun

机构信息

Department of Acquired Immunodeficiency Sydrome and Sexually Transmitted Disease, Liaoning Centers for Disease Control and Prevention, Shenyang 110005, China.

出版信息

Zhonghua Yu Fang Yi Xue Za Zhi. 2009 Nov;43(11):951-5.

Abstract

OBJECTIVE

To investigate the HIV-1 drug resistance associated mutations and examine the susceptibility of HIV-1 with these mutations to antiretroviral in treatment-naive individuals in Liaoning province from 2004 to 2008.

METHODS

RNA was extracted from 20 plasma samples of diagnosed untreated HIV-1-infected treatment-naive patients by drawing method. After the viral loading (VL) test, the protease and nucleoside reverse transcriptase coding regions were amplified by RT-PCR, nested PCR and sequence analysis directly. Levels of resistance and prevalence were evaluated according to the Stanford University HIV Drug Resistance Database's algorithm (http://hivdb.stanford.edu).

RESULTS

Among the 20 plasma samples, 13 got PCR products because of their VL values higher than 1000 copies/ml.Meanwhile, the 13 samples got 65 sequences by using 5 primers each. Polymorphisms in subtype H and circulating recombinant forms (CRFs) CRF10_CD sequences were identified. An overall prevalence of 30.8% (4/13) resistance to NNRTIs, 7.7% (1/13) to PI and no NRTIs mutations were found. The most frequent substitutions (4/13) in the RT region at positions P225H, K238S, V179D, K238T and a major position I54S in PR implied to a multiple drug-resistance. A71V or L10V only, respectively, substitution in PR was found in 3 samples, but no any worse with drug sensitivity.

CONCLUSION

HIV-1 polymorphisms in subtype H and CRFs CRF10_CD sequences were identified circulating in Liaoning. A major mutation position I54S in PR implied that it would be the time to commence a higher level drug regimen.

摘要

目的

调查2004年至2008年辽宁省初治HIV-1感染者中与HIV-1耐药相关的突变,并检测携带这些突变的HIV-1对抗逆转录病毒药物的敏感性。

方法

采用抽取法从20例确诊未治疗的HIV-1感染初治患者的血浆样本中提取RNA。进行病毒载量(VL)检测后,通过RT-PCR、巢式PCR和直接序列分析扩增蛋白酶和核苷类逆转录酶编码区。根据斯坦福大学HIV耐药数据库的算法(http://hivdb.stanford.edu)评估耐药水平和流行率。

结果

20份血浆样本中,13份因VL值高于1000拷贝/ml获得PCR产物。同时,这13份样本每份使用5对引物共获得65条序列。鉴定出H亚型和循环重组型(CRF)CRF10_CD序列中的多态性。对非核苷类逆转录酶抑制剂(NNRTIs)的总体耐药率为30.8%(4/13),对蛋白酶抑制剂(PI)的耐药率为7.7%(1/13),未发现核苷类逆转录酶抑制剂(NRTIs)突变。RT区最常见的替换(4/13)发生在P225H、K238S、V179D、K238T位点,PR区的一个主要位点I54S提示多重耐药。3份样本中PR区分别仅发现A71V或L10V替换,但药物敏感性无明显下降。

结论

在辽宁发现H亚型和CRF CRF10_CD序列中的HIV-1多态性在流行。PR区的一个主要突变位点I54S提示应开始采用更高水平的药物治疗方案。

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