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肯尼亚城乡地区未接受过抗逆转录病毒治疗的HIV-1感染者中传播性耐药突变的流行情况。

Prevalence of Transmitted Drug Resistance Mutations in HIV-1-Infected Drug-Naive Patients from Urban and Suburban Regions of Kenya.

作者信息

Onsongo Simon, Abidi Syed Hani, Khamadi Samoel, Shah Reena, Kageha Sheila, Ojwang Peter, Ali Syed, Okinda Nancy

机构信息

1 Aga Khan University Hospital , Nairobi, Kenya .

2 Department of Biological and Biomedical Sciences, Aga Khan University , Karachi, Pakistan .

出版信息

AIDS Res Hum Retroviruses. 2016 Mar;32(3):220-5. doi: 10.1089/aid.2015.0026. Epub 2015 Sep 24.

Abstract

HIV was first described in Kenya in 1984-1985. Currently, Kenya has an estimated HIV-1 prevalence of 6.2%. With the introduction of antiretroviral drugs, the survival of most HIV patients has been prolonged markedly. However, this is greatly threatened by increasing rates of antiretroviral dug resistance, which may eventually lead to suboptimal treatment outcomes. The objective of this study was to characterize currently occurring antiretroviral drug resistance mutations among drug-naive patients visiting two referral hospitals in Kenya. Using polymerase chain reaction, the HIV protease gene was amplified from blood samples of 63 study participants. The sequences were used to determine HIV-1 subtype and presence/prevalence of mutations associated with resistance to protease inhibitors. Finally, the protease gene was variably measured using Shannon entropy analysis. Analysis of frequency of HIV-1 subtypes revealed subtype A to be the predominant subtype, while the analysis of drug resistance mutations revealed the presence of four minor drug resistance mutations associated weakly with resistance to protease inhibitors. Among these mutations, L33I was the most prevalent mutation. Shannon entropy analysis revealed high genomic variability, especially in region spanning nucleotides 1-55, 113-170, and 205-240. This study warrants the need for dedicated efforts to improve compliance to antiretroviral therapy and reduce transmitted resistance rates, which will greatly ensure the therapeutic efficacy of antiretroviral drugs.

摘要

1984 - 1985年,肯尼亚首次发现了艾滋病病毒。目前,据估计肯尼亚艾滋病病毒1型的流行率为6.2%。随着抗逆转录病毒药物的引入,大多数艾滋病患者的生存期显著延长。然而,抗逆转录病毒药物耐药率的上升对这一情况构成了严重威胁,这最终可能导致治疗效果不佳。本研究的目的是对肯尼亚两家转诊医院中初治患者目前出现的抗逆转录病毒药物耐药突变进行特征分析。通过聚合酶链反应,从63名研究参与者的血样中扩增出艾滋病病毒蛋白酶基因。这些序列用于确定艾滋病病毒1型亚型以及与蛋白酶抑制剂耐药相关的突变的存在情况/流行率。最后,使用香农熵分析对蛋白酶基因进行可变测量。艾滋病病毒1型亚型频率分析显示A亚型是主要亚型,而耐药突变分析显示存在四个与蛋白酶抑制剂耐药相关性较弱的次要耐药突变。在这些突变中,L33I是最常见的突变。香农熵分析显示基因组具有高度变异性,尤其是在核苷酸1 - 55、113 - 170和205 - 240的区域。本研究表明需要做出专门努力来提高对抗逆转录病毒疗法的依从性并降低传播耐药率,这将极大地确保抗逆转录病毒药物的治疗效果。

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