Laboratory and Statistical Development of Cross-Sectional HIV Incidence Assays

横断面艾滋病毒发病率测定的实验室和统计发展

• 批准号: 8507141
• 负责人: RONALD S BROOKMEYER
• 金额: $ 68.67万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507141
• 关键词: AIDS prevention; AIDS/HIV problem; Affect; Africa South of the Sahara; Algorithms; Anti-Retroviral Agents; Antibodies; Antibody Formation; Automobile Driving; Avidity; Base Sequence; Biological Assay; Biological Markers; Blood specimen; CD4 Lymphocyte Count; Characteristics; Chronic; Clinical Trials; Cohort Studies; Cross-Sectional Studies; Data; Data Analyses; Databases; Development; Disease; Epidemic; Evaluation; Goals; Gold; HIV; HIV Antibodies; HIV Genome; HIV Infections; HIV prevention trial; Hand; Incidence; Individual; Laboratories; Lead; Measurement; Measures; Methodology; Methods; Monitor; Performance; Pharmaceutical Preparations; Phase; Population; Populations at Risk; Prevalence; Prevention; Relative (related person); Research Project Grants; Resolution; Sampling; Science; Sensitivity and Specificity; Serological; Staging; Statistical Bias; Statistical Methods; Statistical Models; Surveillance Methods; Testing; United States; Viral; Viral Load result; Virus Diseases; Work; base; burden of illness; clinically relevant; cost; cost effective; design; high risk; improved; mathematical model; melting; novel; repository; response

DESCRIPTION (provided by applicant): HIV incidence is the rate at which new HIV infections occur in populations. While HIV prevalence measures overall disease burden, HIV incidence tracks the leading edge of the HIV/AIDS epidemic. Accurate HIV incidence estimates are critical for monitoring the HIV/AIDS epidemic, identifying populations at high risk of HIV acquisition, targeting prevention efforts, and designing and evaluating HIV prevention trials. Current methods for cross-sectional HIV incidence determination are insufficiently accurate. Our goal is to develop and validate accurate, cost-effective methods for cross-sectional HIV incidence determination. Our hypothesis is that diverse laboratory assays and robust statistical modeling can be combined to improve the accuracy of cross-sectional HIV incidence estimates. We will focus on analysis of HIV incidence in both subtype B (the major subtype driving the HIV/AIDS epidemic in the United States) and subtype C (the major subtype driving the HIV/AIDS epidemic in sub-Saharan Africa); other subtypes prevalent in sub-Saharan Africa will also be analyzed. The Specific Aims of the project are: Aim 1: Continue to build a repository of diverse, well-characterized samples with information on the duration of HIV infection. Analyze the samples using serologic HIV incidence assays. Aim 2: Further develop and validate a novel high resolution melting (HRM) assay for HIV diversity. Determine whether HIV diversity can be used as a biomarker to differentiate between individuals with recent vs. chronic HIV infection. Aim 3: Use statistical analysis and mathematical modeling to assess the accuracy of methods for HIV incidence determination. Apply those approaches to data from Aim 1 (CD4 cell count, HIV viral load, and data from serologic assays) and Aim 2 (data from the HRM assay) to identify methods for HIV incidence determination that perform well in a wide variety of settings, and to assess their relative costs. Our repository will include samples from at least 19 completed clinical trials, cohort studies, and research projects representing key geographic, demographic, and clinically-relevant populations. Over 10,000 of the samples are already in hand. We will integrate laboratory science with statistical analysis and mathematical modeling in all phases of the project, and will evaluate a broad range of design parameters, including use of individual assays versus multi-assay algorithms, use of different assay cutoffs, and sequential ordering of assays. We believe that this comprehensive approach will lead to identification of accurate and cost-effective methods for cross-sectional HIV incidence determination. ) )

描述（由申请人提供）：艾滋病毒发病率是指人群中新发艾滋病毒感染的比率。虽然艾滋病毒患病率衡量总体疾病负担，但艾滋病毒发病率却追踪艾滋病毒/艾滋病流行的前沿。准确的艾滋病毒发病率估计对于监测艾滋病毒/艾滋病流行、识别感染艾滋病毒的高风险人群、确定预防工作以及设计和评估艾滋病毒预防试验至关重要。目前确定横截面艾滋病毒发病率的方法不够准确。我们的目标是开发和验证准确、具有成本效益的方法来确定横截面艾滋病毒发病率。我们的假设是，可以将不同的实验室检测和强大的统计模型结合起来，以提高横截面艾滋病毒发病率估计的准确性。我们将重点分析 B 亚型（导致美国艾滋病毒/艾滋病流行的主要亚型）和 C 亚型（导致撒哈拉以南非洲艾滋病毒/艾滋病流行的主要亚型）的艾滋病毒发病率；撒哈拉以南非洲地区流行的其他亚型也将得到分析。该项目的具体目标是： 目标 1：继续建立一个多样化、特征明确的样本库，其中包含有关 HIV 感染持续时间的信息。使用血清学 HIV 发病率测定分析样本。 目标 2：进一步开发并验证一种新型的 HIV 多样性高分辨率熔解 (HRM) 检测方法。 确定 HIV 多样性是否可以用作区分近期和慢性 HIV 感染者的生物标志物。 目标 3：使用统计分析和数学模型来评估 HIV 发病率测定方法的准确性。将这些方法应用于目标 1（CD4 细胞计数、HIV 病毒载量和血清学测定数据）和目标 2（HRM 测定数据）的数据，以确定在各种环境中表现良好的 HIV 发病率测定方法，并评估其相对成本。我们的存储库将包括来自至少 19 个已完成的临床试验、队列研究和研究项目的样本，代表关键地理、人口和临床相关人群。目前已有超过 10,000 个样品在手。我们将在项目的所有阶段将实验室科学与统计分析和数学建模相结合，并将评估广泛的设计参数，包括单独测定与多测定算法的使用、不同测定截止值的使用以及测定的顺序排序。我们相信，这种综合方法将有助于确定准确且具有成本效益的横断面艾滋病毒发病率测定方法。 ) )