Laboratory and Statistical Development of Cross-Sectional HIV Incidence Assays

描述(由申请人提供)：艾滋病毒发病率是指在人群中发生新的艾滋病毒感染的比率。虽然艾滋病毒流行率衡量的是总体疾病负担，但艾滋病毒发病率跟踪艾滋病毒/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、确定艾滋病毒感染高危人群、针对预防工作以及设计和评估艾滋病毒预防试验至关重要。目前确定艾滋病毒横断面发病率的方法不够准确。我们的目标是开发和验证准确的、具有成本效益的方法来确定横断面艾滋病毒发病率。我们的假设是，不同的实验室分析和稳健的统计建模可以结合在一起，以提高横断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；还将分析撒哈拉以南非洲流行的其他亚型。该项目的具体目标是：目标1：继续建立一个多样化的、具有良好特征的样本储存库，提供有关艾滋病毒感染持续时间的信息。使用血清HIV发病率分析方法对样本进行分析。目的2：进一步建立和验证一种新的HIV多样性的高分辨熔融(HRM)分析方法。确定艾滋病毒多样性是否可用作区分近期和慢性艾滋病毒感染者的生物标记物。目的3：使用统计分析和数学模型评估HIV发病率测定方法的准确性。将这些方法应用于AIM 1(CD4细胞计数、艾滋病毒病毒载量和血清学检测数据)和AIM 2(人力资源管理检测数据)的数据，以确定在各种情况下表现良好的艾滋病毒发病率确定方法，并评估其相对成本。我们的资料库将包括至少19个已完成的临床试验、队列研究和代表关键地理、人口和临床相关人群的研究项目的样本。超过10,000个样本已经在手中。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，包括使用单个分析与多个分析算法、使用不同的分析截止日期以及分析的顺序排序。我们相信，这一全面的方法将导致确定准确和成本效益高的横断面艾滋病毒发病率确定方法。))

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. ) )