本文選題：人類免疫缺陷病毒Ⅰ型 + 限制性抗原親和力酶聯(lián)免疫方法��； 參考：《中國(guó)疾病預(yù)防控制中心》2013年博士論文

【摘要】：研究背景 利用實(shí)驗(yàn)室檢測(cè)技術(shù)從橫斷而樣本中發(fā)現(xiàn)HIV-1新近感染樣本,從而估算HIV-1新發(fā)感染率的實(shí)驗(yàn)室方法越來越受到重視。目前,普遍使用的BED方法存在影響因素多,假近期感染率較高等問題；為了解決這些問題,最近國(guó)際上研發(fā)出了一種新的親和力方法——限制性抗原親和力酶聯(lián)免疫方法(Limiting antigen avidity enzyme immunoassay, LAg-Avidity EIA),經(jīng)初步評(píng)價(jià)該方法受影響因素較少,誤判率大大降低,可以明顯提高估算的HIV-1新發(fā)感染率的準(zhǔn)確性。 研究目的 一、評(píng)價(jià)LAg-Avidity試劑盒的重復(fù)性和準(zhǔn)確度,探討其在中國(guó)推廣應(yīng)用的可行性； 二、獲得LAg-Avidity方法應(yīng)用于中國(guó)HIV-1新發(fā)感染率計(jì)算所必需的窗口期參數(shù)； 三、研究LAg-Avidity方法應(yīng)用于中國(guó)HIV-1新發(fā)感染率計(jì)算所必需的假近期感染率參數(shù),初步探討CD4+T淋巴細(xì)胞計(jì)數(shù)對(duì)LAg-Avidity方法的影響； 四、研究抗病毒治療對(duì)LAg-Avidity方法準(zhǔn)確性的影響。 研究方法 一、采用試劑盒自帶的質(zhì)控品和校準(zhǔn)品通過檢測(cè)精密度和孔問精密度指標(biāo),評(píng)價(jià)LAg-Avidity試劑的重復(fù)性,通過四位實(shí)驗(yàn)員之間劉BOCA101盤檢測(cè)結(jié)果的一致性,四位實(shí)驗(yàn)員對(duì)該標(biāo)準(zhǔn)盤檢測(cè)結(jié)果的平均值與該標(biāo)準(zhǔn)盤期望值結(jié)果的一致性,進(jìn)一步評(píng)價(jià)試劑盒的重復(fù)性；同時(shí),BOCA101盤的判讀結(jié)果用于評(píng)價(jià)LAg-Avidity試劑的準(zhǔn)確度。 二、通過檢測(cè)531份血清學(xué)陽轉(zhuǎn)隊(duì)列樣本(151個(gè)血清學(xué)陽轉(zhuǎn)感染者),利用SPSS17.0軟件對(duì)檢測(cè)結(jié)果進(jìn)行統(tǒng)計(jì)學(xué)分析,研究LAg-Avidity方法的窗口期。 三、通過檢測(cè)513份已知長(zhǎng)期感染(診斷時(shí)間大于方法學(xué)兩倍窗口期)并且未進(jìn)行抗病毒治療的感染者樣本,研究LAg-Avidity方法的假近期感染率參數(shù)。 四、通過對(duì)720份抗病毒治療不同時(shí)間的病人樣本的檢測(cè),計(jì)算誤判比例,研究抗病毒治療時(shí)間以及治療后病毒載量值與LAg-Avidity方法誤判的關(guān)系。 研究結(jié)果 一、檢測(cè)精密度結(jié)果顯示,經(jīng)過校準(zhǔn)品校準(zhǔn)以后,試劑盒低陽對(duì)照和高陽對(duì)照的ODn值的CV小于10%；不同實(shí)驗(yàn)員實(shí)驗(yàn)結(jié)果的一致性較好,四個(gè)實(shí)驗(yàn)員實(shí)驗(yàn)結(jié)果的平均值與美國(guó)疾病預(yù)防控制中心提供的實(shí)驗(yàn)結(jié)果的相關(guān)性較高,R2為0.9849；孔間精密度結(jié)果顯示,大批量生產(chǎn)的試劑盒可能存在酶聯(lián)板包被量不均勻的情況。準(zhǔn)確性檢驗(yàn)中,試劑盒對(duì)BOCA101盤評(píng)判結(jié)果與預(yù)期值完全一致。 二、LAg-Avidity方法的假近期感染率參數(shù)為0.39%(2/513,95%CI0.00%-0.93%),不受CD4+T細(xì)胞計(jì)數(shù)影響(0/52)。 三、當(dāng)方法學(xué)的臨界值取1.0時(shí),LAg-Avidity方法的窗口期參數(shù)為126天。 四、抗病毒治療對(duì)LAg-Avidity方法影響較大,誤判率為10.00%(72/720,95%CI7.81%-12.19%),誤判率和治療時(shí)間沒有相關(guān)性,治療以后病毒載量值越低(小于等于1000copies/ml)越容易造成誤判。 研究結(jié)論 一、大規(guī)模生產(chǎn)的LAg-Avidity試劑盒重復(fù)性較好,試劑盒準(zhǔn)確度較高,可以在中國(guó)推廣應(yīng)用；但試劑盒質(zhì)量仍有提高的空間。 二、初步獲得了LAg-Avidity方法用于中國(guó)HIV-1新發(fā)感染率估算的核心參數(shù),窗口期為126天,假近期感染率為0.39%；與BED方法相比假近期感染率更低,可以使估算的新發(fā)感染率更接近真實(shí)水平。 三、LAg-Avidity方法不受CD4+T淋巴細(xì)胞計(jì)數(shù)的影響,但易受抗病毒治療的影響,在橫斷面調(diào)查時(shí),應(yīng)刪除已經(jīng)進(jìn)行抗病毒治療的病人樣本。
[Abstract]:Background of the study

HIV - 1 newly infected samples were found in the samples from cross - cutting using laboratory testing techniques , so that the method of estimating HIV - 1 infection rate was more and more attention . At present , there are many problems affecting the commonly used BED method , such as many factors , higher false - term infection rate and higher infection rate .
In order to solve these problems , a new affinity method _ restriction antigen avidity enzyme immunoassay ( LAg - Avidin EIA ) has been developed recently .

Purpose of study

1 . To evaluate the repeatability and accuracy of LAg - Avifauna kit and to explore the feasibility of its popularization and application in China ;


secondly , obtaining a LAg - Avifauna method which is applied to the window period parameters necessary for calculating the new infection rate of HIV - 1 in China ;


Thirdly , the study of LAg - Avifauna method was applied to the calculation of HIV - 1 infection rate in China , and the effect of CD4 + T lymphocyte count on the LAg - Avifauna method was discussed .


Fourthly , the effect of antiviral therapy on the accuracy of LAg - Avidin method was studied .

Research Methods

1 , the repeatability of the LAg - Avidin reagent is evaluated by detecting the precision and the hole - to - precision index by using the quality control substance and the calibrator provided by the kit , and the consistency of the average value of the detection result of the standard disc and the expected value of the standard disc is evaluated by four experimenter , and the repeatability of the kit is further evaluated ;
At the same time , the interpretation of the BOCA101 disc was used to evaluate the accuracy of the LAg - Avidin reagent .

Secondly , through the detection of 531 serologic positive transfer cohort samples ( 151 serologic positive patients ) , the detection results were analyzed statistically by SPSS 17.0 software , and the window period of LAg - Avidin method was studied .

3 . The false - recent infection rate parameters of the LAg - Avidin method were investigated by detecting 513 known long - term infections ( diagnosis time greater than twice the window period of the methodology ) and did not perform anti - viral treatment .

Fourthly , the relationship between the anti - virus treatment time and the value of post - treatment virus load and the LAg - Avidin method was studied by detecting the sample of 720 patients with different time .

Results of the study

1 , the detection precision result shows that after the calibration of the calibration sample , the CV of the ODn value of the kit low - positive control and the high - yang control is less than 10 % ;
The results showed that the correlation between the results of the four experimenters was higher than that of the American Centers for Disease Control and Prevention , and R2 was 0.998 ;
The results of inter - hole precision showed that the kit of mass production may be non - uniform in enzyme linked plates . In the accuracy test , the results of the kit ' s evaluation of BOCA101 disc are completely consistent with the expected value .

The infection rate was 0.39 % ( 2 / 513 , 95 % CI 0.00 % - 0.93 % ) in the LAg - Avidin method , which was not affected by CD4 + T cell count ( 0 / 52 ) .

Thirdly , when the critical value of methodology is 1.0 , the window period parameter of the LAg - Avidin method is 126 days .

4 . The effect of antiviral therapy on the LAg - Avifauna method was greater , the rate of misjudgment was 10.00 % ( 72 / 720 , 95 % CI 7.81 % - 12.19 % ) , the rate of misjudgment and treatment time were not correlated , the lower the value of viral load after treatment ( less than or equal to 1000 copies / ml ) , the easier to misjudgment .

Conclusions of the study

firstly , the repeatability of the LAg - Avifauna kit produced by mass production is good , the accuracy of the kit is high , and the LAg - Avifauna kit can be popularized and applied in China ;
but the quality of the kit still has improved space .

Secondly , the core parameters of the LAg - Avifauna method for HIV - 1 infection in China were obtained . The window duration was 126 days , and the infection rate was 0.39 % .
涓嶣ED鏂規(guī)硶鐩告瘮鍋囪繎鏈熸劅鏌撶巼鏇翠綆,鍙互浣夸及綆楃殑鏂板彂鎰熸煋鐜囨洿鎺ヨ繎鐪熷疄姘村鉤.


3 . The LAg - Avifauna method is not affected by CD4 + T lymphocyte count , but is susceptible to antiviral therapy . In cross - sectional investigation , patients with antiviral therapy should be deleted .
【學(xué)位授予單位】：中國(guó)疾病預(yù)防控制中心
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2013
【分類號(hào)】：R512.91

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本文編號(hào)：2114472