International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA)

描述(由申请人提供)： 背景：这项提案要求继续支持leDEA-SA，这是南部非洲艾滋病毒护理和抗逆转录病毒治疗(ART)项目的一个大型合作网络。目标：(I)提供有关儿童、青少年和成人长期方案有效性的最佳现有数据；(Ii)描述长期方案的耐受性和耐受性，并检查不同的监测和治疗策略，重点是病毒载量和二线抗逆转录病毒疗法；(Iii)描述共病，重点是结核病和癌症；(Iv)跟踪孕妇抗逆转录病毒疗法以及接触抗逆转录病毒药物的非艾滋病毒感染婴儿和受感染婴儿的队列，以及(V)建设该地区的能力。方法：来自7个国家(博茨瓦纳、莱索托、马拉维、莫桑比克、南非共和国、赞比亚、津巴布韦)的20个城市和农村抗逆转录病毒治疗项目将汇集数据，创建一个数据库，其中包括40万名感染艾滋病毒的成年人、1万名青少年、3.6万名儿童和6700名婴儿，其中约70%的患者接受抗逆转录病毒治疗。在南非，艾滋病毒数据将与国家癌症登记处、国家死亡和出生登记处以及结核病登记处联系起来。将分析死亡率、失访、结核病和复发结核病、定义艾滋病的癌症和其他癌症，以及生育力、CD4细胞轨迹、限制治疗的毒性、对二线抗逆转录病毒治疗的反应以及未能通过抗逆转录病毒治疗的成人和儿童的耐药性突变。将在孕妇和婴儿的子队列中检查产前和出生后接触抗逆转录病毒药物的趋势、妊娠结局(包括早产和人体测量)、喂养做法和18个月后的生长情况。我们将调查为癌症患者提供的护理，并比较不同的浸润性宫颈癌筛查策略。统计分析将考虑数据的层次性、数据缺失和后续损失、相互竞争的风险和与时间相关的混淆，并将开发新的方法。积累的成果将用于建立儿童、青少年和成人抗逆转录病毒治疗的数学模型并将其参数化，该模型将反映南部非洲艾滋病毒护理和抗逆转录病毒治疗的现实情况，并为卫生政策提供参考。 相关性： 南部非洲是受艾滋病毒疫情影响最严重的地区。自2004年以来，各国政府和其他方面的努力导致艾滋病毒/艾滋病干预措施大幅增加，特别是抗逆转录病毒治疗。迫切需要进行业务、临床和公共卫生研究，以指导长期向包括孕妇、婴儿、儿童和青少年在内的许多有需要的患者提供艾滋病毒护理和抗逆转录病毒治疗。

DESCRIPTION (provided by applicant): Background: This proposal asks for continued support of leDEA-SA, a large collaborative network of HIV care and antiretroviral treatment (ART) programs in Southern Africa. Aims: (i) to provide the best available data on long-term program effectiveness in children, adolescents and adults; (ii) to describe long-term regimen durability and tolerability and examine different monitoring and treatment strategies, with a focus on viral load and second-line ART; (iii) to describe co-morbidities, focusing on tuberculosis and cancer and (iv) to follow up pregnant women on ART and cohorts of ART-exposed non HIV-infected infants and infected infants, and (v) to build capacity in the region. Methods: 20 urban and rural ART programs from 7 countries (Botswana, Lesotho, Malawi, Mozambique, Republic of South Africa, Zambia, Zimbabwe) with follow-up up to 10 years will pool data to create a database of 400,000 HIV-infected adults, 10,000 adolescents, 36,000 children and 6,700 infants, with about 70% of patients on ART. In South Africa, HIV data will be linked to the National Cancer Registry, National Death and Birth Registers, and the Tuberculosis Register. Mortality, loss to follow-up, tuberculosis and recurrent tuberculosis, and AIDS-defining and other cancers will be analyzed, as well as fertility, CD4 cell trajectories, treatment-limiting toxicities, response to second-line ART and resistance mutations in adults and children failing ART. Trends in exposure to antenatal and postnatal ARVs, pregnancy outcomes including prematurity and anthropometry, feeding practices and growth over 18 months will be examined in sub- cohorts of pregnant women and infants. We will survey the provision of care to cancer patients, and compare different screening strategies for invasive cervical cancer. Statistical analyses will consider the hierarchical nature of the data, missing data and loss to follow-up, competing risks and time-dependent confounding, and new methods will be developed. Accumulating results will be used to build and parameterize a mathematical model of ART in children, adolescents and adults, which will reflect the realities of HIV care and ART in Southern Africa, and inform health policy. RELEVANCE: Southern Africa is the region most heavily affected by the HIV epidemic. Since 2004, efforts by governments and others have resulted in a massive increase in HIV/AIDS interventions and particularly ART. Operational, clinical and public health research is urgently needed to guide the long-term delivery of HIV care and ART to the many patients in need, including pregnant women, infants, children and adolescents.