限制性抗原亲和力方法（LAg-avidity EIA）应用于我国哨点HIV新发感染检测的研究

发布时间：2018-06-27 03:37

本文选题：限制性抗原亲和力酶免法 + BED捕获酶免法　；参考：《中国疾病预防控制中心》2014年硕士论文

【摘要】：背景准确的实验室HIV新发感染检测方法对于获得横断面人群的HIV发病率,掌握HIV的流行动态、发现高发病率地区和高危人群,评价干预措施实施的效果具有重要意义。新一代HIV新发感染检测方法-限制性抗原亲和力酶免法(Limiting antigen avidity enzyme immunoassay, LAg-avidity EIA)在准确性方面较现在普遍应用的BED捕获酶免法(BED Capture enzyme immunoassay, BED CEIA)方法有较大改进,对既往感染者错分率低,受疾病进展和抗逆转录病毒治疗(Antiretroviral Treatment,ART)影响小,因此可以获得更加准确的HIV发病率。目的一、比较LAg与BED方法在我国哨点横断面人群中应用结果,为该方法在我国的推广应用和可能存在的问题提供参考；二、结合哨点流行病学信息,对2011年哨点HIV感染率最高的MSM人群的HIV感染状况和行为因素进行分析,为今后在该人群中开展有效防治措施提供依据。材料和方法一、收集2011年14省市自治区国家级HIV监测哨点MSM、DUS、FSW和STD四类高危人群的新发感染检测样本1442份,用LAg方法进行检测,将LAg方法HIV新发感染判定结果与BED方法HIV新发感染判定结果进行比较(BED结果来自各省检测结果),比较两种方法HIV新发感染判定结果的一致性；按照WHO推荐的新发感染实验室检测方法HIV发病率计算公式,应用国际发表的LAg方法校正系数和我国发表BED方法系数分别计算LAg方法和BED方法获得四类人群的HIV发病率,比较两种方法获得HIV发病率是否存在差异；二、应用前期研究中获得LAg方法不同校正系数计算四类人群的HIV发病率,探讨发病率计算的影响因素。不同校正系数分别为LAg方法以不同ODn值为判定界值(cutoff值)时国际和我国研究数据(数据未发表)；三、从“艾滋病综合防治数据信息系统”下载13省市自治区2011年MSM哨点问卷信息19613份,对各省市MSM人群的人口学信息、行为因素和血清学检测结果进行描述；分析人口行为因素及梅毒、HCV感染对BED和LAg判定结果的影响；对HIV感染和新发感染的相关因素进行多元Logistic回归分析。结果一、1442份样本,LAg判定新发感染312份,新发感染比例为21.6%；BED判定404份为新发感染,新发感染比例为28.0%,配对Χ2检验两种方法判定结果存在差异,LAg判定新发感染比例低于BED。两种方法判定结果一致率为89.9%, Kappa值0.73。LAg和BED方法对不同人群新发感染判定结果存在差异：HIV感染率较高的MSM和DUS人群,LAg和BED方法新发感染判定结果不一致,LAg判定新发感染比例低于BED。MSM人群检测样本795份,LAg判定新发感染261份,BED判定新发感染323份,新发感染比例分别为32.8%、40.6%；DUS人群检测样本468份,LAg和BED判定新发感染分别3.0%(14/468)和7.9%(37/468)。FSW和STD人群两种方法新发感染判定结果没有统计学差异,可能与这类人群HIV感染率低,纳入新发感染检测样本数量少有关。87份FSW样本,LAg和BED判定新发感染样本数分别为10份和14份；92份STD样本两种方法判定新发感染样本数分别为27和30份。二、LAg和BED方法获得的四类人群HIV发病率没有统计学差异,MSM、 DUS、FSW和STD人群,LAg获得HIV发病率分别为3.94%(95%CI:3.32-4.56)、0.07%(95%CI:-0.01-0.15%)、0.06%(95%CI:0.02-0.09%)和0.17%(95%CI:0.10-0.24%); BED获得HIV发病率分别为3.49%(95%CI:2.99-3.99%)、0.04%(95%CI:-0.01-0.15%)、0.04%(95%CI:0.01-0.07%)和0.12%(95%CI：0.07-0.18%)。三、LAg方法不同国际校正系数计算获得HIV发病率没有统计学差异,LAg方法分别以1.0、1.5、1.75为cutoff值对应国际系数计算四类人群HIV发病率结果：MSM人群HIV发病率分别为4.18%(95%CI：3.45-4.91%)、3.94%(95%CI：3.32-4.56%)和3.76%(95%CI:3.22-4.31%); DUS人群获得的发病率分别为0.02%(95%CI：-0.04-0.08%)、0.07%(95%CI：-0.01-0.15%)和0.07%(95%CI:-0.01-0.14%); FSW人群发病率分别为：0.03%(95%CI：0-0.07%)、0.06%(95%CI：0.02-0.09%)和0.05%(95%CI：0.02-0.09%),STD人群不同cutoff值获得HIV-1发病率均为0.17%。LAg分别以ODn值1.0、1.5为cutoff值对应我国校正系数计算获得MSM HIV发病率2.97%(95%CI：2.54-3.41%)和2.92(95%CI:2.54-3.29%), DUS、FSW和STD人群HIV发病率分别为0.02%(95%CI:-0.02-0.07%)/0.03%(95%CI:-0.03-0.09%).0.02%(95%CI:0-0.05%)/0.04%(95%CI：0.01-0.07%)和0.12%(95%CI：0.06-0.18%)/0.13%(95%CI：0.08-0.18%),各人群LAg方法不同cutoff值对应我国系数计算HIV发病率基本一致。LAg方法cutoff值为1.0和1.5时,我国系数计算MSM人群HIV发病率低于相同cutoff值国际系数计算结果,差异有统计学意义；其余人群我国和国际系数计算结果没有统计学差异。四、13省市哨点MSM调查对象HIV抗体阳性率为5.01%,平均年龄29.3岁,52.5%为21～30岁人群,62.1%未婚；汉族占95.8%,高中及以上文化程度占76.9%,艾滋病知识知晓率为91.3%。近6个月,同性性行为、同性商业性行为和异性性行为发生率分别为84.1%、8.0%和31.3%,梅毒感染率为8.1%。不同地区调查对象人口学特征和行为因素分布具有不同质性。五、13省市哨点MSM人群LAg判定新发感染217人,平均年龄30.2岁；BED检测判定新发感染277人,平均年龄30.3岁。两种方法判定HIV新发感染者在年龄、婚姻、户籍、民族、文化程度、行为因素、梅毒、HCV感染等因素的分布没有统计学差异。HIV新发人群50.0%以上年龄在21～30岁；与异性的婚姻状况61.0%未婚；70.0%为以上为本地户籍；90.0%以上为汉族。BED和LAg判定新发感染人群近6个月同性性行为、同性商业性行为和异性性行为发生率分别为87.4%/89.4%、7.6%/6.9%和27.8%/29.0%。BED判定HIV新发感染人群中梅毒阳性率为20.9%,LAg为19.4%。BED和LAg方法判定HIV新发感染者HCV抗体阳性率均为1.4%。六、多因素Logistic回归分析结果,地区、26岁以上,外地户籍,初中文化程度,近6个月与同性发生性行为,无保护性性行为以及梅毒感染7个因素是HIV感染的危险因素；居住时间是HIV感染的保护因素。地区、外地户籍,近6个月与同性发生性行为,无保护性性行为以及梅毒感染是BED判定新发感染危险因素。地区、外地户籍,初中文化,近6个月与同性发生性行为,无保护性性行为以及梅毒感染6个因素是LAg判定的HIV新发感染危险因素。结论一、BED和LAg方法对哨点横断面样本的判定结果存在差异；LAg判定的新发感染样本数少于BED,可能与LAg对既往感染者的误判率低有关；二、国际公布LAg方法校正系数计算我国哨点人群HIV发病率与我国人群BED校正系数计算我国哨点人群HIV发病率结果基本一致。三、除LAg界值在1.0和1.5时我国系数获得MSM HIV发病率显著低于国际系数计算结果之外,其余人群不同界值我国系数和国际系数获得HIV发病率无统计学差异,与BED结果也没有统计学差异。仍需进一步获得我国人群LAg方法的窗口期和FRR。四、MSM人群HIV感染率较高,高危行为普遍存在,部分地区梅毒感染率处于较高水平,仍需进一步加强MSM人群的行为干预。人口行为因素及梅毒、HCV感染对BED和LAg判定结果无影响。HIV感染者和新发感染者在人口学特征上存在差异；LAg和BED方法判定HIV新发感染危险因素在人口学特征上也存在差异。
[Abstract]:background
HIV new infection detection method in the laboratory is very important to obtain the incidence of HIV in the cross section population, to grasp the epidemic trend of HIV, to find the high incidence area and high risk population, to evaluate the effect of the intervention measures. The new generation of HIV new infection detection method, the restriction antigen affinity enzyme immunoassay (Limiting antigen avidit) Y enzyme immunoassay, LAg-avidity EIA) has a greater improvement in accuracy than the commonly used BED capture enzyme immunoassay (BED Capture enzyme immunoassay, BED CEIA) method, which has a low error rate for previously infected persons, less affected by disease progression and antiretroviral therapy, and thus can be obtained more. Accurate incidence of HIV.
objective
First, compare the application results of LAg and BED in sentinel cross sectional population in China, and provide reference for the popularization and application of this method in China.
Two, in combination with sentinel epidemiological information, the HIV infection status and behavioral factors of the MSM population with the highest HIV infection rate in 2011 were analyzed to provide the basis for the effective prevention and control measures in the population in the future.
Materials and methods
First, we collected 1442 new infection detection samples from four high-risk groups of high risk groups in 14 provinces and municipalities of 2011 in 14 provinces and municipalities. LAg method was used to detect 1442 new infection samples. The LAg method HIV new infection determination results were compared with the BED method HIV new infection determination results (BED results came from the provincial test results), and two methods HI were compared. V is consistent with the results of new infection determination; according to the formula of the HIV incidence of the new infection laboratory detection method recommended by WHO, the international published LAg method correction coefficient and the BED method coefficient in our country, the HIV incidence of the four groups of people is calculated by the LAg method and the BED method respectively, and the two methods are compared to obtain the HIV incidence. There are differences.
Two, using different correction coefficients of LAg method to calculate the HIV incidence of the group of four groups in the previous study, and discuss the influencing factors of the incidence of the incidence. The different correction coefficients are the LAg method with different ODn values as the boundary value (cutoff value), and the research data of our country (the data are not published).
Three, from the "AIDS comprehensive prevention and control data information system" to download the 2011 MSM sentinel questionnaire information from 13 provinces and municipalities, to describe the demographic information, behavioral factors and serological results of MSM population in various provinces and cities, and to analyze the effects of population behavior factors and syphilis, HCV infection on the results of BED and LAg, and HIV infection and Multivariate Logistic regression analysis was used to identify the related factors of new infection.
Result
One, 1442 samples, LAg identified 312 new infection, 21.6% new hair infection, 404 new hair infection, 28% new hair infection, 2 test of 2 test, and two methods, LAg determined that the ratio of new infection was lower than that of BED. two, and the Kappa value 0.73.LAg and BED methods were not good. There were differences in the results of new infection determination in the same group: MSM and DUS with high HIV infection rate were not consistent with the new infection determination results of LAg and BED, LAg determined that the proportion of new infection was 795 lower than that of BED.MSM population, LAg determined new infection 261, BED determined 323 NEW hair infection, and the ratio of new hair infection was 32.8%, 40.6%; DUS respectively. There were 468 samples of population detection, LAg and BED determined that there were no statistical differences between the two new infection methods of new hair infection, 3% (14/468) and 7.9% (37/468).FSW and STD respectively. It may be low in HIV infection rate in this group, and the number of new infection samples is less related to.87 FSW samples, LAg and BED determine the number of new infection samples, respectively. The total number of new infections was 27 and 30, respectively, for 10 and 14 samples and 92 STD samples two methods.
Two, the incidence of HIV in four groups of people with LAg and BED was not statistically different. The incidence of HIV in MSM, DUS, FSW and STD groups was 3.94% (95%CI:3.32-4.56), 0.07% (95%CI:-0.01-0.15%), 0.06% (95%CI:0.02-0.09%) and 0.17%, respectively, 3.49% (0.04%), respectively. -0.15%), 0.04% (95%CI:0.01-0.07%) and 0.12% (95%CI:0.07-0.18%).
Three, there was no statistical difference in the incidence of HIV in the LAg method, and the incidence of HIV in the four groups was calculated with the LAg method corresponding to the international coefficient of cutoff. The incidence of HIV in the MSM population was 4.18% (95%CI:3.45-4.91%), 3.94% (95%CI:3.32-4.56%) and 3.76% (95%CI:3.22-4.31%), respectively; The incidence of the group was 0.02% (95%CI:-0.04-0.08%), 0.07% (95%CI:-0.01-0.15%) and 0.07% (95%CI:-0.01-0.14%), and the incidence of FSW in the population was 0.03% (95%CI:0-0.07%), 0.06% (95%CI:0.02-0.09%) and 0.05% (95%CI:0.02-0.09%). The incidence of HIV-1 in STD crowds was all 0.17%.LAg on ODn values, respectively. 5 the incidence of MSM HIV was 2.97% (95%CI:2.54-3.41%) and 2.92 (95%CI:2.54-3.29%), DUS, FSW and STD were 0.02% (95%CI:-0.02-0.07%) /0.03% (95%CI:-0.03-0.09%) and 0.12% (0.12%) for the calculation of the correction coefficient in China. 8-0.18%), different cutoff values of different population LAg corresponding to China's coefficient calculation HIV incidence rate basically consistent.LAg method cutoff value is 1 and 1.5, our country coefficient calculation MSM population HIV incidence rate is lower than the same cutoff international coefficient calculation result, the difference has statistical significance; the rest of the population of our country and international coefficient calculation results are not statistically significant Difference.
Four, the positive rate of HIV antibody was 5.01%, the average age was 5.01%, the average age was 29.3, 52.5% was 21~30 years old, 62.1% was unmarried, the Han nationality accounted for 95.8%, the high school and above was 76.9%, the awareness rate of AIDS knowledge was nearly 6 months, homosexual sex, sex commercial sex and sex behavior were 84.1%, 8%, respectively, 8%. And 31.3%, syphilis infection rate was 8.1%.. The distribution of demographic characteristics and behavioral factors in different regions had different quality.
Five, 13 provinces and cities sentinel MSM population LAg determine 217 new infection, the average age of 30.2 years, BED detection and determination of new infection 277 people, the average age of 30.3 years. Two methods to determine the HIV new hair infection in the age, marriage, household registration, ethnic, cultural, behavioral factors, syphilis, HCV infection and other factors, there are no statistical differences in the distribution of.HIV new population 50 More than 21~30 years of age were in the age of 21~30; 61% were unmarried with the opposite sex marriage status; 70% was the local domicile; more than 90% of the Han.BED and LAg determined the sex behavior of the newly infected people for nearly 6 months, and the rate of sexual commercial sex and heterosexual behavior was 87.4%/89.4%, 7.6%/6.9% and 27.8%/29.0%.BED determined the new infection of the people. The positive rate of syphilis in the group was 20.9%, LAg was 19.4%.BED and LAg method. The positive rate of HCV antibody in new HIV infection was 1.4%..
Six, multiple factor Logistic regression analysis results, areas over 26 years old, foreign domicile, junior high school education, nearly 6 months with sex sex, unprotected sex and 7 factors of syphilis infection are risk factors for HIV infection; residence time is the protective factor of HIV infection. Unprotected sex and syphilis infection are the risk factors for BED to determine new infection. Region, local household registration, junior high school culture, sexual behavior of the same sex in the last 6 months, unprotected sex and 6 factors of syphilis infection are the risk factors for the new infection of HIV determined by LAg.
conclusion
First, there is a difference between the BED and LAg methods for sentinel cross sectional samples; the number of new infection samples determined by LAg is less than that of BED, which may be related to the low miscarriage rate of LAg to the previous infection.
Two, the correction coefficient of LAg method was published internationally to calculate the incidence of HIV in Chinese sentinel population and the BED correction coefficient of Chinese population to calculate the incidence of HIV in Chinese sentinel population.
Three, in addition to the LAg boundary value of 1 and 1.5, the incidence of MSM HIV in China is significantly lower than that of the international coefficient calculation. There is no statistical difference in the incidence of HIV in the other population values and international coefficients in the rest of the population, and there is no statistical difference from the BED results. It is still necessary to further obtain the window period and FRR. of the LAg method in the population of our country.
Four, the rate of HIV infection in the MSM population is high, high risk behavior is prevalent, and the rate of syphilis infection is at a high level in some areas. It is still necessary to further strengthen the behavioral intervention of the MSM population. Population behavior factors and syphilis, HCV infection has no influence on the.HIV infection and the new hair Dyer in the demographic characteristics of the BED and LAg determinant; LAg and BED square There were differences in demographic characteristics between HIV and new risk factors.
【学位授予单位】：中国疾病预防控制中心
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.91

【参考文献】