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The M50I polymorphic substitution in association with the R263K mutation in HIV-1 subtype B integrase increases drug resistance but does not restore viral replicative fitness.M50I 多态性取代与 HIV-1 亚型 B 整合酶中的 R263K 突变相关,增加了药物耐药性,但不能恢复病毒复制适应性。
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Molecular diversity of HIV-1 and surveillance of transmitted drug resistance variants among treatment Naïve patients, 5 years after active introduction of HAART in Kuala Lumpur, Malaysia.马来西亚吉隆坡在积极引入高效抗逆转录病毒治疗(HAART)5 年后,治疗初治患者中 HIV-1 的分子多样性和传播耐药变异体的监测。
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1型人类免疫缺陷病毒序列多样性对抗逆转录病毒治疗结果的影响。

Impact of human immunodeficiency virus type-1 sequence diversity on antiretroviral therapy outcomes.

作者信息

Langs-Barlow Allison, Paintsil Elijah

机构信息

Department of Pediatrics, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520, USA.

Departments of Pediatrics and Pharmacology, Yale University School of Medicine, Child Health Research Center, 464 Congress Ave, New Haven, CT 06520, USA.

出版信息

Viruses. 2014 Oct 20;6(10):3855-72. doi: 10.3390/v6103855.

DOI:10.3390/v6103855
PMID:25333465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4213566/
Abstract

Worldwide circulating HIV-1 genomes show extensive variation represented by different subtypes, polymorphisms and drug-resistant strains. Reports on the impact of sequence variation on antiretroviral therapy (ART) outcomes are mixed. In this review, we summarize relevant published data from both resource-rich and resource-limited countries in the last 10 years on the impact of HIV-1 sequence diversity on treatment outcomes. The prevalence of transmission of drug resistant mutations (DRMs) varies considerably, ranging from 0% to 27% worldwide. Factors such as geographic location, access and availability to ART, duration since inception of treatment programs, quality of care, risk-taking behaviors, mode of transmission, and viral subtype all dictate the prevalence in a particular geographical region. Although HIV-1 subtype may not be a good predictor of treatment outcome, review of emerging evidence supports the fact that HIV-1 genome sequence-resulting from natural polymorphisms or drug-associated mutations-matters when it comes to treatment outcomes. Therefore, continued surveillance of drug resistant variants in both treatment-naïve and treatment-experienced populations is needed to reduce the transmission of DRMs and to optimize the efficacy of the current ART armamentarium.

摘要

全球流行的HIV-1基因组呈现出广泛的变异,表现为不同的亚型、多态性和耐药菌株。关于序列变异对抗逆转录病毒疗法(ART)疗效影响的报道不一。在本综述中,我们总结了过去10年中来自资源丰富和资源有限国家的相关已发表数据,内容涉及HIV-1序列多样性对治疗结果的影响。耐药突变(DRM)的传播流行率差异很大,在全球范围内从0%到27%不等。地理位置、获得抗逆转录病毒疗法的机会和可及性、治疗项目启动后的持续时间、护理质量、冒险行为、传播方式以及病毒亚型等因素,都会决定特定地理区域内的流行率。虽然HIV-1亚型可能不是治疗结果的良好预测指标,但对新出现证据的回顾支持这样一个事实,即无论是自然多态性还是与药物相关的突变所导致的HIV-1基因组序列,在治疗结果方面都很重要。因此,需要对初治和经治人群中的耐药变异体持续进行监测,以减少耐药突变的传播,并优化当前抗逆转录病毒疗法的疗效。