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HIV-1 drug resistance mutations detection and HIV-1 subtype G report by using next-generation sequencing platform.
Microbial Pathogenesis ( IF 3.8 ) Pub Date : 2020-04-29 , DOI: 10.1016/j.micpath.2020.104221
Mohammad Gholami 1 , NeginHosseini Rouzbahani 2 , SiamakMirab Samiee 3 , Katayoun Tayeri 4 , Khodayar Ghorban 5 , Alireza Dolatyar Dehkharghani 6 , Ali Akbar Gholami 7 , Farzaneh Moshiri 8 , Arash Sattari 9 , Maryam Dadmanesh 10 , Minoo Mohraz 4
Affiliation  

BACKGROUND Based on world health organization (WHO) recommend, drug resistance assay should be performed in initial of treatment and after treatment for administering and monitoring of anti-retroviral regime in HIV-1 infected patients. MATERIAL AND METHOD NGS analyses were performed on forty-one plasma samples from HIV-1 affected patients using the Sentosa SQ HIV genotyping assay (Vela-Diagnostics, Germany). This system comprises a semi-automated Ion torrent based platform and the sequencing results were analyzed based on ANRS, REGA and Stanford drug resistance algorithms. Phylogenetic analysis was analyzed based on https://comet.lih.lu database as well as MEGA5 Software. RESULTS Drug resistances were identified in thirty-three samples (80%) out of forty-one samples. The Phylogenetic analysis results showed that CRF-35AD (94%) and subtypes B (2.4%) and G (2.4%) were dominant subtypes in this study. NRTI and NNRTI associated dominant mutations were M184I/V and K103 N.High-level resistance to lamivudine (3 TC) and Emtricitabine (FTC) were detected in 34.3% of patients while 53.1% were resistant to Efavirenz (EFV) and Nevirapine (NVP). The Protease inhibitor (PI) minor and major mutations were not reported but more than 95% of samples had polymorphisms mutation in K20R, M36I, H69K, L89 M positions. These mutations are subtype dependent and completely are absent in subtype B virus. The secondary mutations were reported in positions of E157Q, S230 N, and T97A of integrase gene and four samples represent low-level resistance to integrase strand transfer inhibitor (INSTI). CONCLUSIONS This is the first preliminary evaluation of HIV-1 drug resistance mutation (DRM) by using the Sentosa SQ HIV Genotyping Assay in Iran. The NGS represent a promising tool for the accurate detection of DRMs of CRF-35AD that is dominant subtype in Iranian HIV-1 infected population and for the first time revealed HIV-1 subtype G in Iranian population. In the present study polymorphic mutation in the position of K20R, M36I, H69K, L89 M were properly reported in CRF35AD that is dominant in Iranian HIV patients.

中文翻译:

使用下一代测序平台进行HIV-1耐药性突变检测和HIV-1 G亚型报告。

背景技术根据世界卫生组织(WHO)的建议,应在治疗初期和治疗后进行耐药性测定,以管理和监测HIV-1感染患者的抗逆转录病毒疗法。材料与方法使用圣淘沙SQ HIV基因分型测定法(Vela-Diagnostics,德国)对来自HIV-1感染患者的41份血浆样品进行NGS分析。该系统包括一个基于半自动离子激流的平台,并基于ANRS,REGA和Stanford耐药算法对测序结果进行了分析。系统发育分析基于https://comet.lih.lu数据库以及MEGA5软件进行分析。结果在41个样本中,有33个样本(80%)鉴定出耐药性。系统发育分析结果表明,CRF-35AD(94%)和亚型B(2。4%)和G(2.4%)是本研究的主要亚型。NRTI和NNRTI相关的显性突变为M184I / V和K103 N.在34.3%的患者中检测到对拉米夫定(3 TC)和恩曲他滨(FTC)的高水平耐药性,对Efavirenz(EFV)和Nevirapine(NVP)有53.1%的耐药性)。没有报道蛋白酶抑制剂(PI)的次要和主要突变,但是超过95%的样品在K20R,M36I,H69K,L89 M位置具有多态性突变。这些突变是亚型依赖性的,在B型亚型病毒中完全不存在。在整合酶基因的E157Q,S230 N和T97A的位置报道了二级突变,四个样品代表了对整合酶链转移抑制剂(INSTI)的低水平抗性。结论这是在伊朗使用Sentosa SQ HIV基因分型分析法对HIV-1耐药性突变(DRM)的首次初步评估。NGS代表着一种有前途的工具,可用于准确检测CRF-35AD的DRM,该DRM是伊朗HIV-1感染人群的主要亚型,也是首次在伊朗人群中显示HIV-1 G的亚型。在本研究中,正确报道了在伊朗HIV患者中占主导地位的CRF35AD中K20R,M36I,H69K,L89 M的多态性突变。
更新日期:2020-04-30
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