本文選題：HIV耐藥毒株 + 流行現(xiàn)狀�。� 參考：《濟(jì)南大學(xué)》2013年碩士論文

【摘要】：目的 艾滋病抗病毒治療是延長病人生命、提高艾滋病病毒感染者生存質(zhì)量、預(yù)防艾滋病二代傳播的主要措施，本研究通過對山東省接受抗病毒治療的艾滋病病毒（HIV）感染者進(jìn)行免疫學(xué)、病毒載量和耐藥基因型檢測，旨在了解山東省接受艾滋病抗病毒治療人群中HIV耐藥現(xiàn)狀，分析產(chǎn)生耐藥的原因及其影響因素，，從而為提高抗病毒治療工作質(zhì)量、延長病人壽命和提高病人生存質(zhì)量等相關(guān)工作提供參考依據(jù)。 方法 于2012年5～10月采集的山東省17地市所有正在接受抗病毒治療且治療時(shí)間≥6個月的病人的抗凝全血，使用流式細(xì)胞學(xué)技術(shù)對采集的抗凝全血進(jìn)行CD4+T淋巴細(xì)胞計(jì)數(shù)。使用熒光實(shí)時(shí)定量PCR（NucliSens EasyQ）方法對血漿進(jìn)行HIV病毒載量檢測，對其中病毒載量≥1000拷貝/ml的血樣分別用RT-PCR和巢式PCR擴(kuò)增方法，對HIV蛋白酶（PR）全長和部分逆轉(zhuǎn)錄酶（RT）基因進(jìn)行檢測，將擴(kuò)增陽性的樣本進(jìn)行基因測序，最后將所測序列提交美國斯坦福大學(xué)耐藥基因數(shù)據(jù)庫進(jìn)行耐藥相關(guān)突變位點(diǎn)的產(chǎn)生情況及其對各類藥物敏感性的對比分析。將調(diào)查對象流行病學(xué)資料和血樣實(shí)驗(yàn)室檢測結(jié)果相結(jié)合，通過Epidata軟件建立數(shù)據(jù)庫，應(yīng)用SPSS17.0統(tǒng)計(jì)軟件對相關(guān)資料進(jìn)行系統(tǒng)分析。 結(jié)果 截至2012年10月31日，全省正在接受抗病毒治療的病人有1245人，其中抗病毒治療時(shí)間≥6個月病人的有926人，本研究共采集治療人群血樣926份，其中7人流行病學(xué)資料丟失或不全，919例接受艾滋病治療調(diào)查對象資料詳細(xì)，符合納入標(biāo)準(zhǔn)。對載量≥1000cp/ml的85份血樣進(jìn)行耐藥檢測，17例病人擴(kuò)增失�。ú挥�(jì)入耐藥率的計(jì)算），共獲得68例病人的耐藥檢測結(jié)果，其中有49例出現(xiàn)耐藥突變位點(diǎn)，在產(chǎn)生耐藥突變位點(diǎn)的樣本中發(fā)現(xiàn)33例樣本產(chǎn)生耐藥，耐藥率為3.7%（33/902）。在33例耐藥病人中有22例服用核苷類逆轉(zhuǎn)錄酶藥物（NNRT）的病人出現(xiàn)相關(guān)耐藥突變位點(diǎn)，其中M184V突變在所有服用NRTI的病人中出現(xiàn)頻率最高81.8%（18/22）；在33例服用非核苷類逆轉(zhuǎn)錄酶（NNRTI）治療方案的病人中36.4%（12/33）的病人出現(xiàn)V179D耐藥突變位點(diǎn)，突變頻率最高。從治療效果上看，病毒抑制率為89.3%（821/919），治療效果比較好； 對耐藥性與CD4+T淋巴細(xì)胞計(jì)數(shù)和病毒載量結(jié)果分析，發(fā)現(xiàn)耐藥性的產(chǎn)生引起CD4+T淋巴細(xì)胞計(jì)數(shù)下降和病毒載量上升；對治療病人的一般人口學(xué)特征感染途徑、治療年限、治療方案和治療亞型等進(jìn)行單因素危險(xiǎn)因素分析，未發(fā)現(xiàn)有統(tǒng)計(jì)學(xué)差異；對年齡、性別、治療年限、治療方案等進(jìn)行多因素相關(guān)分析發(fā)現(xiàn)性別和治療年限是耐藥突變產(chǎn)生的獨(dú)立危險(xiǎn)因素。 結(jié)論 1.山東省艾滋病抗病毒治療病人中有49例病人產(chǎn)生耐藥突變位點(diǎn)，其中有33例病人產(chǎn)生耐藥，耐藥率為3.7%，總體耐藥率處于較低水平 2.本次研究中M184V和V179D出現(xiàn)頻率最高，研究發(fā)現(xiàn)的突變位點(diǎn)均為常見耐藥突變位點(diǎn)。 3.山東省艾滋病抗病毒治療病人的病毒抑制率為89.3%，抗病毒治療取得很好的療效； 4.單因素分析發(fā)現(xiàn)耐藥性的產(chǎn)生引起CD4+T淋巴細(xì)胞計(jì)數(shù)的下降和病毒載量結(jié)果的上升。 5.單因素分析未發(fā)現(xiàn)一般人口學(xué)特征、傳染途徑、治療方案、治療年限等與耐藥性的產(chǎn)生有顯著性差異；在年齡、性別、治療年限和治療方案等因素同時(shí)存在時(shí)進(jìn)行多因素分析結(jié)果顯示年齡和治療方案與耐藥性產(chǎn)生沒有顯著性差異，性別和治療年限是與耐藥性產(chǎn)生有關(guān)的主要影響因素。
[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.

【學(xué)位授予單位】：濟(jì)南大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R512.91

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