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

描述（由申请人提供）： 背景资料：该提案要求继续支持南部非洲艾滋病毒护理和抗逆转录病毒治疗（ART）计划的大型合作网络leDEA-SA。目的：（i）提供关于儿童、青少年和成人长期方案有效性的现有最佳数据;（ii）描述长期方案的持久性和耐受性，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）描述合并症，重点是结核病和癌症;（iv）对接受抗逆转录病毒治疗的孕妇以及接触抗逆转录病毒治疗的未感染艾滋病毒婴儿和受感染婴儿队列进行跟踪;（v）在该地区进行能力建设。研究方法：来自7个国家的20个城市和农村ART项目（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）将进行长达10年的随访，汇集数据，建立一个数据库，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6,700名婴儿，约70%的患者接受抗逆转录病毒治疗。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、失访率、结核病和复发性结核病、艾滋病定义的癌症和其他癌症，以及生育率、CD 4细胞轨迹、治疗限制性毒性、对二线抗逆转录病毒疗法的反应以及抗逆转录病毒疗法失败的成人和儿童的耐药性突变。并以孕妇及婴儿为研究对象，研究他们在十八个月内的喂养习惯及生长情况。我们将调查为癌症患者提供的护理，并比较浸润性宫颈癌的不同筛查策略。统计分析将考虑数据的分层性质、缺失数据和失访、竞争风险和时间依赖性混杂因素，并将开发新方法。积累的成果将用于建立儿童、青少年和成人抗逆转录病毒疗法的数学模型并提供参数，该模型将反映南部非洲艾滋病毒护理和抗逆转录病毒疗法的现实，并为卫生政策提供信息。 相关性： 南部非洲是受艾滋病毒流行病影响最严重的区域。自2004年以来，各国政府和其他方面的努力已导致艾滋病毒/艾滋病干预措施，特别是抗逆转录病毒疗法大幅增加。迫切需要开展业务、临床和公共卫生研究，以指导向许多有需要的患者，包括孕妇、婴儿、儿童和青少年，提供长期的艾滋病毒护理和抗逆转录病毒疗法。

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.