HIV耐药毒株在山东省艾滋病抗病毒治疗人群中的流行现状及相关因素分析

发布时间：2018-05-06 09:07

本文选题：HIV耐药毒株 + 流行现状　；参考：《济南大学》2013年硕士论文

【摘要】：目的艾滋病抗病毒治疗是延长病人生命、提高艾滋病病毒感染者生存质量、预防艾滋病二代传播的主要措施，本研究通过对山东省接受抗病毒治疗的艾滋病病毒（HIV）感染者进行免疫学、病毒载量和耐药基因型检测，旨在了解山东省接受艾滋病抗病毒治疗人群中HIV耐药现状，分析产生耐药的原因及其影响因素，，从而为提高抗病毒治疗工作质量、延长病人寿命和提高病人生存质量等相关工作提供参考依据。方法于2012年5～10月采集的山东省17地市所有正在接受抗病毒治疗且治疗时间≥6个月的病人的抗凝全血，使用流式细胞学技术对采集的抗凝全血进行CD4+T淋巴细胞计数。使用荧光实时定量PCR（NucliSens EasyQ）方法对血浆进行HIV病毒载量检测，对其中病毒载量≥1000拷贝/ml的血样分别用RT-PCR和巢式PCR扩增方法，对HIV蛋白酶（PR）全长和部分逆转录酶（RT）基因进行检测，将扩增阳性的样本进行基因测序，最后将所测序列提交美国斯坦福大学耐药基因数据库进行耐药相关突变位点的产生情况及其对各类药物敏感性的对比分析。将调查对象流行病学资料和血样实验室检测结果相结合，通过Epidata软件建立数据库，应用SPSS17.0统计软件对相关资料进行系统分析。结果截至2012年10月31日，全省正在接受抗病毒治疗的病人有1245人，其中抗病毒治疗时间≥6个月病人的有926人，本研究共采集治疗人群血样926份，其中7人流行病学资料丢失或不全，919例接受艾滋病治疗调查对象资料详细，符合纳入标准。对载量≥1000cp/ml的85份血样进行耐药检测，17例病人扩增失败（不计入耐药率的计算），共获得68例病人的耐药检测结果，其中有49例出现耐药突变位点，在产生耐药突变位点的样本中发现33例样本产生耐药，耐药率为3.7%（33/902）。在33例耐药病人中有22例服用核苷类逆转录酶药物（NNRT）的病人出现相关耐药突变位点，其中M184V突变在所有服用NRTI的病人中出现频率最高81.8%（18/22）；在33例服用非核苷类逆转录酶（NNRTI）治疗方案的病人中36.4%（12/33）的病人出现V179D耐药突变位点，突变频率最高。从治疗效果上看，病毒抑制率为89.3%（821/919），治疗效果比较好；对耐药性与CD4+T淋巴细胞计数和病毒载量结果分析，发现耐药性的产生引起CD4+T淋巴细胞计数下降和病毒载量上升；对治疗病人的一般人口学特征感染途径、治疗年限、治疗方案和治疗亚型等进行单因素危险因素分析，未发现有统计学差异；对年龄、性别、治疗年限、治疗方案等进行多因素相关分析发现性别和治疗年限是耐药突变产生的独立危险因素。结论 1.山东省艾滋病抗病毒治疗病人中有49例病人产生耐药突变位点，其中有33例病人产生耐药，耐药率为3.7%，总体耐药率处于较低水平 2.本次研究中M184V和V179D出现频率最高，研究发现的突变位点均为常见耐药突变位点。 3.山东省艾滋病抗病毒治疗病人的病毒抑制率为89.3%，抗病毒治疗取得很好的疗效； 4.单因素分析发现耐药性的产生引起CD4+T淋巴细胞计数的下降和病毒载量结果的上升。 5.单因素分析未发现一般人口学特征、传染途径、治疗方案、治疗年限等与耐药性的产生有显著性差异；在年龄、性别、治疗年限和治疗方案等因素同时存在时进行多因素分析结果显示年龄和治疗方案与耐药性产生没有显著性差异，性别和治疗年限是与耐药性产生有关的主要影响因素。
[Abstract]:objective
AIDS antiviral therapy is the main measure to prolong the life of the patients, improve the quality of life of the HIV infected people and prevent the spread of the two generation of AIDS. In this study, the HIV (HIV) infected people in Shandong province were immunological, viral load and drug resistance genotypes, aiming to understand the acceptance of AIDS in Shandong province. The current status of HIV resistance in the patients with antiviral therapy, analysis of the causes of drug resistance and its influencing factors, provide reference for improving the quality of antiviral treatment, prolonging the life span of the patients and improving the quality of the patient's survival.
Method
All the anti anticoagulant blood of the patients who were treated with antiviral treatment and treatment for more than 6 months were collected in 17 city of Shandong province in 5~10 months of 2012. Flow cytometry was used to count the CD4+T lymphocyte count of the collected anticoagulant whole blood. The HIV virus load was detected by the fluorescence real-time quantitative PCR (NucliSens EasyQ) method. The blood samples with viral load or more than 1000 copies of /ml were amplified by RT-PCR and nested PCR, respectively. The whole length of HIV protease (PR) and the partial reverse transcriptase (RT) gene were detected. The positive samples were amplified and sequenced. Finally, the sequence was submitted to the drug-resistant gene database of Stanford University in the United States for resistance related mutation sites. The production situation and the comparison and analysis of the sensitivity of various kinds of drugs were analyzed. The database was established by Epidata software and the related data were systematically analyzed by SPSS17.0 software.
Result
As of October 31, 2012, there were 1245 patients receiving antiviral treatment in the province, of which 926 were treated with antiviral therapy for more than 6 months. This study collected 926 blood samples from the treatment group, of which 7 were lost or incomplete, and 919 cases of AIDS treatment were in detail and were in line with the inclusion criteria. 85 samples of blood samples with more than 1000cp/ml were tested for resistance. 17 cases were failed (not counting the rate of resistance). A total of 68 cases of drug resistance detection were obtained. Among them, 49 cases had resistance mutation sites. 33 samples were found to be drug-resistant and 3.7% (33/902) was found in the samples that produced resistance mutation sites. In 33 cases of drug-resistant patients. There were 22 patients taking nucleoside reverse transcriptase (NNRT) related resistance mutation sites, of which M184V mutation occurred at the highest frequency of 81.8% (18/22) in all patients taking NRTI, and 36.4% (12/33) of 33 patients who took non nucleoside reverse transcriptase (NNRTI) therapy had V179D resistance mutation sites, mutation frequency The rate of virus inhibition was 89.3% (821/919), and the treatment effect was better.
The analysis of drug resistance and CD4+T lymphocyte count and viral load results showed that the emergence of drug resistance resulted in the decrease of CD4+T lymphocyte count and the increase of viral load, and the analysis of single factor risk factors for the general demographic characteristics of infection, treatment, treatment and treatment subtypes for patients with general demographic characteristics was not found to be statistically significant Multi factor correlation analysis of age, sex, treatment years and treatment plans found that sex and treatment years were independent risk factors for drug resistance mutation.
conclusion
1. of the patients with AIDS antiviral treatment in Shandong Province, 49 patients have resistance mutation sites, of which 33 cases are resistant to drug resistance, the resistance rate is 3.7%, and the overall resistance rate is at a low level.
2. the frequency of M184V and V179D was the highest in this study. The mutation sites found in the study were common resistance mutations.
3. the virus inhibition rate of AIDS patients in Shandong is 89.3%, and antiviral treatment has achieved good results.
4. univariate analysis showed that the production of resistance resulted in a decrease in CD4+T lymphocyte count and an increase in viral load.
5. single factor analysis did not find general demographic characteristics, infection pathways, treatment programs, treatment years and so on, and there were significant differences in the generation of drug resistance. The results of multiple factors analysis in the same age, sex, treatment years and treatment schemes showed that there was no significant difference between age and treatment plan and drug resistance. And duration of treatment are the main factors related to drug resistance.

【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.91

【参考文献】