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目的:调查分析浙江省主要地区(杭州、宁波和温州)的抗病毒治疗病人的耐药基因变异情况,以进一步指导抗病毒药物的选用。方法:选取三地区接受抗病毒治疗的274例患者,对病毒抑制失败(即病毒载量大于1000 IU/ml)的样本进行HIV蛋白酶(PR)全长和部分逆转录酶(RT)基因区进行RT-PCR和巢式PCR扩增并测序。使用斯坦福大学HIVdb程序在线分析耐药相关突变位点,并分析对各药物的敏感性。结果:病毒未抑制率为10.9%(30/274),最终获得29份序列用于耐药基因分析。发现蛋白酶抑制剂(PI)、核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)最主要耐药突变类型分别为M46I、M184V和Y181C/V,三类药物的耐药率分别为0.4%(1/273),7.3%(20/273)和7.7%(21/273),总耐药率为7.7%(21/273)。21个个体发生耐药,其中4.8%(1/21)的个体对PI耐药,95.2%(20/21)对NRTI耐药,所有人均对NNRTI耐药,90.5%(19/21)的个体表现对NRTI和NNRTI的双重耐药。结论:整体而言,浙江省主要地区抗病毒治疗病人中HIV毒株耐药处于较低水平,但耐药突变呈多样化,耐药个体NRTI和NNRTI双重耐药突出,但对PI药物普遍敏感,应结合实际科学合理用药。
Objective: To investigate the variation of drug resistance genes in patients with antiviral therapy in major areas of Zhejiang Province (Hangzhou, Ningbo and Wenzhou) to further guide the selection of antiviral drugs. METHODS: A total of 274 patients receiving antiretroviral therapy in three regions were enrolled in a HIV protease (PR) full-length and partial reverse transcriptase (RT) genomic region of samples that failed viral inhibition (ie, viral load greater than 1000 IU / ml) RT-PCR and nested PCR amplification and sequencing. The Stanford University HIVdb program was used to analyze resistance-related mutation sites online and to analyze the sensitivity to each drug. Results: The uninhibited rate of virus was 10.9% (30/274). Finally, 29 sequences were obtained for drug resistance gene analysis. The main types of resistance mutations found in protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) were M46I, M184V and Y181C / V, respectively The resistance rates were 0.4% (1/273), 7.3% (20/273) and 7.7% (21/273), respectively. The overall resistance rate was 7.7% (21/273). Twenty-one individuals were drug resistant, of which 4.8% (1/21) were resistant to PI, 95.2% (20/21) were resistant to NRTI, all were resistant to NNRTI, and 90.5% (19/21) Performance of dual drug resistance to NRTI and NNRTI. Conclusion: Overall, the HIV-resistant strains of HIV-infected patients in Zhejiang province are at a low level, but the drug-resistant mutations are diversified. The dual drug resistance of NRTI and NNRTI in drug-resistant individuals is prominent but sensitive to PI drugs , Should be combined with the actual scientific and rational drug use.