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从接受依非韦伦治疗失败的感染者中分离出的 HIV-1 株中,与依曲韦林耐药相关的突变的流行情况:B 亚型和非 B 亚型遗传变异体之间的比较。

Prevalence of etravirine resistance associated mutations in HIV-1 strains isolated from infected individuals failing efavirenz: comparison between subtype B and non-B genetic variants.

机构信息

Laboratory of Virology, Coimbra University Hospitals, Coimbra, Portugal.

出版信息

J Med Virol. 2012 Apr;84(4):551-4. doi: 10.1002/jmv.23232.

Abstract

Etravirine (ETR) is a non-nucleoside analogue reverse transcriptase inhibitor (NNRTI) with a high genetic barrier to the development of resistance and with potential activity against Human immunodeficiency virus type 1 (HIV-1) strains resistant to first-generation NNRTIs. The objective of this study was to investigate the prevalence of ETR resistance associated mutations (RAMs) in HIV-1 strains isolated from infected individuals failing efavirenz (EFV), as well as to evaluate possible differences in the distribution of ETR RAMs between subtype B and non-B genetic variants. Nucleotide sequences of the protease and partial reverse transcriptase (RT) coding regions of the pol gene of 55 HIV-1 strains isolated from infected individuals failing EFV on regular follow-up at a reference center in Portugal, were retrospectively analyzed. The most prevalent ETR RAMs observed were L100I, V90I, and K101E, with a prevalence of 16.4% (n = 9), 9.1% (n = 5), and 5.5% (n = 3), respectively. Overall, 47.3% (n = 26) of the nucleotide sequences had at least one ETR RAM: 38.2% (n = 21) had one ETR RAM, 7.3% (n = 4) had two ETR RAMs and 1.8% (n = 1) had three ETR RAMs. No statistically significant differences were found in the distribution of ETR RAMs between subtype B and non-B genetic variants. The results demonstrate that ETR rescue therapy is a viable option in treatment-experienced individuals failing EFV and suggests that ETR may be equally useful in HIV-1 infections caused by different genetic variants.

摘要

依曲韦林(ETR)是一种非核苷类逆转录酶抑制剂(NNRTI),具有较高的遗传耐药屏障,对第一代 NNRTIs 耐药的人类免疫缺陷病毒 1 型(HIV-1)株具有潜在活性。本研究旨在调查在因依非韦伦(EFV)失败而感染的个体中分离出的 HIV-1 株中与 ETR 耐药相关的突变(RAM)的流行率,以及评估 B 亚型和非 B 遗传变异体之间 ETR RAM 分布的可能差异。对葡萄牙一家参考中心定期随访的因 EFV 失败而感染的 55 例 HIV-1 株的蛋白酶和部分逆转录酶(RT)编码区的核苷酸序列进行了回顾性分析。观察到最常见的 ETR RAM 是 L100I、V90I 和 K101E,其流行率分别为 16.4%(n=9)、9.1%(n=5)和 5.5%(n=3)。总体而言,47.3%(n=26)的核苷酸序列至少有一种 ETR RAM:38.2%(n=21)有一种 ETR RAM,7.3%(n=4)有两种 ETR RAM,1.8%(n=1)有三种 ETR RAM。在 B 亚型和非 B 遗传变异体之间,ETR RAM 的分布没有统计学上的显著差异。结果表明,ETR 挽救治疗是治疗经验丰富的 EFV 失败个体的可行选择,并表明 ETR 在不同遗传变异体引起的 HIV-1 感染中可能同样有用。

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