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韩国新诊断为 HIV/AIDS 的抗逆转录病毒药物初治患者中 HIV-1 整合酶区的遗传变异。

Genetic variation of the HIV-1 integrase region in newly diagnosed anti-retroviral drug-naïve patients with HIV/AIDS in Korea.

机构信息

Division of AIDS, Department of Immunology and Pathology, National Institute of Health, Seoul, South Korea.

出版信息

Clin Microbiol Infect. 2011 Aug;17(8):1155-9. doi: 10.1111/j.1469-0691.2010.03392.x. Epub 2010 Dec 3.

DOI:10.1111/j.1469-0691.2010.03392.x
PMID:20946407
Abstract

The survival time of HIV/AIDS patients in Korea has increased since HAART (highly active anti-retroviral therapy) was introduced. However, the occurrence of drug-resistant strains requires new anti-retroviral drugs, one of which, an integrase inhibitor (INI), was approved by the US Food and Drug Administration (FDA) in 2007. INIs have been used for therapy in many countries and are about to be employed in Korea. Therefore, it is important to identify basic mutant variants prior to the introduction of INIs in order to estimate their efficacy. To monitor potential drug-resistant INI mutations in Korean HIV/AIDS patients, the polymorphism of the int gene was investigated together with the pol gene using a genotypic assay for 75 randomly selected Korean HIV-1 patients newly diagnosed in 2007. The drug-resistant mutation sequences were analysed using the Stanford HIV DB and the International AIDS Society resistance testing-USA panel (IAS-USA). Seventy strains of Korean subtype B were compared with foreign subtype-B strains, and there were no significantly different variants of the int gene region in the study population. Major mutation sites in the integrase (E92Q, F121Y, G140A/S, Y143C/R, Q148H/R/K and N155H) were not detected, and only a few minor mutation sites (L74M, V151I, E157Q, V165I, I203M, S230N and D232N) were identified in 21 strains (28%). Resistance due to mutations in the pol gene was observed in a single strain (1.3%) resistant to protease inhibitors (PIs) and in four strains (5.3%) resistant to reverse transcriptase inhibitors (RTIs). In summary, this demonstrates that INIs will be susceptible to drug naïve HIV/AIDS patients in Korea.

摘要

自高效抗逆转录病毒疗法(HAART)问世以来,韩国艾滋病毒/艾滋病患者的存活时间有所延长。然而,耐药株的出现需要新的抗逆转录病毒药物,其中一种整合酶抑制剂(INI)于 2007 年获得美国食品和药物管理局(FDA)批准。INIs 已在许多国家用于治疗,并即将在韩国使用。因此,在引入 INIs 之前,确定基本的突变变体对于估计其疗效非常重要。为了监测韩国艾滋病毒/艾滋病患者潜在的耐药 INI 突变,使用基因分型检测方法对 2007 年新诊断的 75 名韩国 HIV-1 患者的 pol 基因和 int 基因进行了研究。使用斯坦福 HIV DB 和国际艾滋病协会耐药性检测-美国小组(IAS-USA)分析耐药突变序列。将 70 株韩国 B 亚型与国外 B 亚型进行比较,研究人群中 int 基因区域没有明显不同的变异。未检测到整合酶中的主要突变位点(E92Q、F121Y、G140A/S、Y143C/R、Q148H/R/K 和 N155H),仅在 21 株(28%)中发现少数次要突变位点(L74M、V151I、E157Q、V165I、I203M、S230N 和 D232N)。在 1 株(1.3%)对蛋白酶抑制剂(PI)耐药和 4 株(5.3%)对逆转录酶抑制剂(RTI)耐药的菌株中观察到由于 pol 基因突变引起的耐药性。综上所述,这表明 INIs 对韩国初治的 HIV/AIDS 患者是敏感的。

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