【作者】 谢天胜；

【导师】 吴南屏；

【作者基本信息】 浙江大学 ， 内科学， 2014， 博士

【摘要】 第一部分结合居民健康体检的社区艾滋病抗体普遍检测研究背景：是否艾滋病普遍检测的争议已经持续了25年之久,2012年美国预防服务工作组(USPSTF)发布指南性文件,强烈建议在所有成人中开展普遍HIV抗体检测。暗娼等桥梁人群的作用,使中国艾滋病从高危、重点人群向普通人群扩散,由于潜伏期长、无症状,使艾滋病的主动发现更为困难,当前疫情监测体系难以完全触及普通人群,急需探索普通人群的全民HIV抗体筛查策略,及早发现传染病、及时控制传染源、减少传播和降低感染率。目的：探索结合浙江省现行的居民健康体检工程的HIV抗体普遍筛查策略,发现潜在阳性人群,及时掌握区域人群艾滋病感染率、分布及其相关风险因素,为摸清艾滋病流行率打下基础。方法：2010年6月到2012年5月,采用分层多阶段整群抽样策略,结合健康体检,完成社区居民HIV抗体普遍检测,并收集人口学、抗体检测结果。用SPSS18.0进行数据清洗和分析,一般信息用描述性分析,参照2000年中国人口标准结构标化感染率,不同感染率之间比较用卡方检验,相关影响因素用Logistic回归分析。结果：在1113030纳入检测人群中,确诊HIV阳性310例,感染率为3.45/10000,其中男性为5.62/10000,女性为1.17/10000,相对于男性人群,女性人群的艾滋病感染风险相对较低(ARR,0.16,p<0.001)。不同年龄层的艾滋病感染率也具有显著差异,25-34岁年龄层感染率最高为9.30/10000,相比对<15岁人群,其他年龄组人群的艾滋病感染风险均较高(ARR范围从2.49-25.69),尤其是25-34与35-44年龄组人群高(ARR,25.69,p<0.001和ARR18.48,p<0.001),在老年人群中发现55-64岁和65岁以上年龄组人群的艾滋病感染率分别为2.04/10000和0.78/10000。在中等GDP地区,25-44岁,男性人群感染率高。310例阳性人群中203为既往诊断阳性病例,107例为本次普遍检测新诊断出病例,本次普遍检测贡献率达34.52%。相比于本地户籍阳性人群,非本地户籍具有具有如下特点：平均年龄小10岁、未婚比例高、文化程度低等。结论：1)本研究通过在浙江省居民健康体检基础上增加HIV抗体检测,成功的在大规模人群(111万)完成HIV抗体普遍检测；2)基于分层多阶段整群抽样策略,在111万人群中,诊断阳性310例,艾滋病感染率为3.45/10000,尚属低流行区,同时率的分布将为后续疫情监测、干预研究提供基础资料；3)诊断的310例阳性中,107例(34.52%)为新诊断病例,普遍检测有助于发现潜在阳性人群。第二部分基于社区的艾滋病强化随访效果研究背景：高效抗逆转录病毒治疗(HAART)对减少艾滋病病人死亡和提高病人生活质量发挥了极其重要的作用,但较差的服药依从性使HAART的疗效大打折扣。因此,开展有效病人管理探索,以期较好的完成病人随访管理指标,加强接受抗病毒治疗病人的服药督促、社会心理支持,提高治疗效果,有利于降低病死率。目的：本研究旨在建立基于社区的抗病毒治疗随访干预措施,评估不同随访管理模式下接受HAART患者的用药依从性情况、随访指标体系和治疗效果。了解HAART人群依从性状况和相关影响因素,从而在降低病死率方面进行探索。方法：2012年3月到2013年6月,强化随访组建立的社区-疾控-专科医院的“三位一体”阳性随访管理措施,常规随访组以当前的“疾控”随访为主要模式。评估12个月后依从性变化、随访管理指标变化以及治疗效果。采用SPSS18.0进行数据分析,运用描述统计、卡方检验、Logistic回归、t检验等统计方法。结果：在强化随访组和常规随访组各纳入165例和84例,强化随访组的依从性从83.03%提高到91.52%,常规随访组依从性从82.14%提高到83.33%,两者有显著性差异(χ2=3.733,P=0.045),综合比较前后依从性变化情况,发现强化随访组变好比例为16.36%,常规随访组为7.14%,有统计学差异性(χ2=4.117,P=0.042)。对HAART人群中的关键指标分析发现,相比于常规随访组,强化随访组在坚持治疗比例、完成7次随访比例、CD4检测比例、病毒载量检测比例等主要指标的完成情况均优于常规随访组。在免疫学指标观察中,强化随访组和常规随访组CD4+T细胞计数均显著上升(t=-3.028,P=0.003；t=-2.327,P=0.022)；强化随访组活化系统表达(CD8+CD38+)比例37.38±8.68下降到34.40±11.53,具有显著性差异(t=1.987,P=0.048)；强化随访组IL7-CD127系统(CD4+CD127+)比例从23.22±7.11上升到27.69±11.72,具有显著性差异(t=-3.237,P=0.001)；常规随访组均没有显著性差异。结论：1)经12个月随访,强化随访组依从性的改善显著优于常规随访组(χ2=4.117,P=0.042)；2)相比于常规随访组,强化随访组坚持治疗比例、完成7次随访比例、CD4检测比例、病毒载量检测比例等主要指标的完成情况均优于常规随访组；3)经过12个月的治疗,两组研究对象的CD4+T细胞数均能显著提高,然而强化随访组在免疫活化和IL7-CD127系统的免疫恢复情况显著优于常规随访组。第三部分艾滋病阳性的老年人群流行病学与病死率分析背景：随着人口老龄化的到来,预期寿命的提高和生活质量的改善,使得该人群性活跃程度出现了极大的变化,中国老年人感染病例快速增长的趋势,但这个人群的流行、发病、死亡特点仍不清楚。目的：系统回顾分析老年艾滋病感染者病人流行特征,比较死亡原因及病死率,掌握浙江省老年感染人群特征,为针对性防治提供依据。方法：根据浙江省疫情分布和流行病学因素,收集2000年1月1日-2012年12月30日报告的1115例艾滋病阳性病例,其中196例为老年(≥50岁),应用SPSS18.0进行数据分析,采用卡方检验、生存分析方法。结果：发现≥50岁组占整个艾滋病阳性的比例成逐年上升的趋势,特别是在2000年后,从0上升到2012年的22.45%,性传播为主,占82.65%。相对与<50岁组,>50岁组诊断时CD4数值显著低(291.64vs.363.63p<0.05).更多的人发现即处于发病状态(51.02%vs.34.06%p<0.05)。生存分析估计≥50岁组存活时间为11.54±0.49年；<50岁组为13.85±0.46年,两组之间Log Rank (Mantel-Cox)检验卡方值为3.83,两者有显著差异性(P<0.05)。结论：1)老年病例发现数逐年上升,性传播为主,老年群体艾滋病问题不容忽视；2)老年阳性人群估计生存时间为11.54±0.49年,不能及时早期诊断和本身的基础疾病,可能是该人群估计存活时间短、病死率高的主要原因；3)加强对老年人探索主动筛查策略或扩大监测体系的年龄谱,以便及时发现老年病人,及时治疗,降低老年艾滋病人病死率。更多还原

【Abstract】 Part I Community based HIV universal testingObjective:This study used a large-scale human immunodeficiency virus (HIV) antibody screening in a field investigation among more than1million individuals to explore the universal HIV testing in general population, and to understand the HIV infection situation.Methods:We used a multi-stage stratified random cluster sampling method in a community-based investigation of30sample points within9counties in Zhejiang province. The HIV antibody was detected and demographic information was collected together with health exam plan (HEP).Results: Of1113030persons screened for HIV,310were positive (adjusted rate,3.45/10000;95%confidence interval [CI],3.41-3.48). The HIV infection rate was higher in men than that in women at all age group; those in the25-34and35-44age groups were highest (compared with the <15age group, the adjusted odds ratios were25.69and18.48, respectively). The HIV infection rate in the medium gross domestic product (GDP) counties (adjusted rate,5.28/10000;95%CI,4.53-6.04) was significantly higher than those in the high and low GDP counties among the male25-34and35-44age groups. Migrant HIV-positive individuals were10years younger, and with lower education than native HIV-positive individuals. Also they did not have fixed sexual partners.Conclusion: Adding HIV antibody testing to HEP in the general population can enlarge coverage of HIV testing and find potential people living with HIV. Focus could be placed on male migrants of25-44years old in HIV control strategies, especially in industrial activity districts. Part II The effect of community based enhanced follow-up managementObject: To establish the community based ART intervention measures, and through a comparative between the research group and the control group, evaluation patients compliance situation, follow-up index system and the treatment effect in different follow-up mode.Methods: Based on the current "CDC" follow-up mode, newly establish "community-CDC-hospital" follow-up mode. After12months intervention, we evaluation the compliance changes, follow-up index changes and treatment effect. Using SPSS18.0data analysis tools include descriptive statistics, chi-square test, Logistic regression and t-test.Results:165cases and84cases were enrolled into the enhanced follow-up group and routine follow-up group respectively, after12months intervention, compliance in enhanced follow-up group increased from83.03%to91.52%, compliance in routine follow-up increased from82.14%to83.33%, significant difference can be seen (X2=3.733, P=0.045). According to the annual assessment analysis of the key indicators of HAART population, compared to the routin follow-up group, completion of main indexes in the enhanced follow-up group adhere to treatment, the completion of the7times follow-up ratio, CD4detection ratio, the proportion of viral load testing of the routine follow-up group. At the same time, in enhanced group CD4+T cell raised from 347.59±137.46to424.74±172.38(t=-3.028, P=0.003), while in routine group also increased significantly (t=-2.327, P=0.022). Enhanced follow-up group activation system (CD8+CD38+) expression ratio of37.38±8.68was reduced to34.40±11.53, and had significant difference (t=1.987, P=0.048); enhanced follow-up IL7-CD127system (CD4+CD127+) increased from23.22±7.11to27.69±11.72, with significant difference between before and after (t=-3.237, P=0.001).Conclusion: Community based enhanced follow-up intervention measures are feasibility and validity, through standardized management, by improving the compliance and social support, therapeutic effect became better, promote immune reconstitution, in this way to reduce the death rate mortality. Part III Epidemiological Analysis of Older Adults with HIVObjective: The aims of this study were to systematically review epidemiological characteristics in older people living with HIV/AIDS (PLWHA) in low endemic areas of China, analyze the causes of death and mortality, and provide a basis for targeted prevention in these populations.Methods:Nine counties representative of the distribution and epidemiological factors of the HIV epidemic in Zhejiang Province were selected, and data from1115HIV-positive individuals, including196older people (≥50years), who were confirmed as PLWHA from January1st,2000to December31th,2012, were retrospectively analyzed.Results:The proportion of older PLWHA increased from0%in2000to22.45%in2012. Sexual transmission was the main route, accounting for82.65%of infectious in this group. Compared with the younger group (range from14to49years old), the older group had significantly lower CD4+cell counts (291.64vs.363.63; P<0.001) when first diagnosed, and more of this group presented in the AIDS state with opportunistic infections (51.02%vs.34.06%; P<0.001). In the older group,25(12.76%) patients died directly of AIDS and171(87.24%) were censored, and in the younger group50(5.44%) patients died directly of AIDS and869(94.56%) were censored. Estimated survival time since HIV diagnosis in the older group was11.54±0.49years (95%confidence interval [CI]10.59-12.50), while in the younger group it was13.85±0.46years (95%CI12.94-14.76), the log rank (Mantel-Cox) test gave a chi-square value of3.83, and there was significant difference between the groups (P<0.05).Conclusion:The number of older PLWHA increased steadily over the study period in low HIV endemic provinces of a developing country. Later discovery and preexisting disease perhaps contributed to a shorter estimated survival time for older PLWHA and higher mortality.更多还原