Properties of HIV-1 DNA/RNA Assays for Detecting HIV Infection in Infants

用于检测婴儿 HIV 感染的 HIV-1 DNA/RNA 检测的特性

• 批准号: 8071405
• 负责人: RAJI BALASUBRAMANIAN
• 金额: $ 26.01万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8071405
• 关键词: Address; Africa; Age; Anti-Retroviral Agents; Area; Asia; Biological Assay; Birth; Birth Weight; Breast Feeding; CD4 Lymphocyte Count; Characteristics; Complex; Complication; DNA; DNA amplification; Data; Data Analyses; Data Set; Databases; Detection; Diagnosis; Diagnostic; Diagnostic tests; Disadvantaged; Early Diagnosis; Epidemic; Europe; Evaluation; Foundations; Future; Goals; Gold; Guidelines; HIV; HIV Infections; HIV Seropositivity; HIV-1; Heterogeneity; High Prevalence; Highly Active Antiretroviral Therapy; Human Milk; Human Virus; Human immunodeficiency virus test; Infant; Infection; International; Investigation; Knowledge; Life; Light; Mediating; Medical; Meta-Analysis; Mothers; Pathogenesis; Performance; Population; Pregnancy; Prevention; Property; Prophylactic treatment; RNA; RNA amplification; Regimen; Research Personnel; Resources; Risk Estimate; Risk Factors; Sample Size; Satellite Viruses; Schedule; Signal Transduction; Statistical Models; Testing; Time; Time Factors; Variant; Vertical Disease Transmission; Viral; Viral Load result; Work; base; cohort; feeding; information gathering; insight; interdisciplinary collaboration; novel; prevent; statistics; stem; transmission process; virus pathogenesis

DESCRIPTION (provided by applicant): UNAIDS statistics estimate that approximately 800,000 infants are infected with HIV annually, with 90% of infections occurring in resource-limited settings. Virtually all HIV infections in infants are attributed to mother-to-child transmission (MTCT), which can occur during the periods of pregnancy, birth, or breast- feeding. In the absence of treatment, approximately 25% of infants born to HIV-positive mothers will be infected with HIV. In resource-rich settings, treatment with highly-active anti-retroviral therapies (HAART) has reduced the transmission rate to under 2%; However, determining the optimal time to test and providing early, timely treatment remain areas of concern. The "gold standard" tests for diagnosis of HIV infection in infants are HIV-1 DNA and RNA assays. Previous work has shown that the time to positive detection of infection varies significantly among infected infants. Current knowledge is based on small studies conducted primarily in the U.S./Europe and in populations who are, at most, exposed to monotherapy regimens. Previous work on the timing of MTCT suffers from several limitations, including limited sample size and the use of ad hoc strategies. We propose to characterize assays to detect HIV infection in infants and to investigate the timing of MTCT, based on a combined analysis of data from several cohorts of HIV-exposed infants. Central to our proposal is the formation of an interdisciplinary collaboration of investigators from several cohorts including approximately 5,800 HIV-positive formula-fed and breastfed infants born to HIV-positive mothers representing populations in the U.S., Europe, Africa, and Asia. The resulting large database will enable statistical analyses to evaluate the performance of DNA/RNA assays in diverse settings, including in populations exposed to HAART and in settings where non-B subtype infections dominate. We will apply novel statistical models for the estimation of timing of MTCT that overcome disadvantages inherent in previously employed ad hoc strategies. Specifically, our proposal addresses the following: Aim 1 - Characterization and comparison of the distribution of time to positive signal of HIV-1 DNA and RNA assays in HIV-1 infected, non-breastfed infants; Aim 2a - Estimation of timing of MTCT of HIV in HIV-infected, non- breastfed infants; and Aim 2b - Estimation of the timing of MTCT of HIV in HIV-infected, breastfed infants. In each aim, special emphasis will be placed on evaluating maternal/infant factors, including type of maternal/infant antiretroviral treatment, HIV subtype, and mode of delivery; mother's age, HIV-1 viral load, and CD4 cell count; and infant's CD% and birth weight. The results gathered from Aim 2b, will serve as a foundation for a larger meta-analysis of risks and factors involved in MTCT of HIV in populations where breastfeeding is the norm. IMPACT: A better understanding of the characteristics of diagnostic assays and the timing of MTCT will guide strategies to optimize HIV diagnostic testing in infants in various populations, and will inform the best approaches for scheduling prophylaxis, particularly when resources are limited. PUBLIC HEALTH RELEVANCE: Prevention of mother-to-child transmission of HIV is a fundamental component of the global effort to stem the HIV epidemic. Critical challenges in this endeavor include knowledge of the accuracy of commonly used HIV diagnostic tests in infants and insight into the mechanism and timing of mother-to-child transmission of HIV. This proposal utilizes in-depth statistical analyses to address these issues based on combined data from several large cohorts of HIV-positive mothers and their infants in the U.S., Europe, Africa, and Asia.

描述（由申请人提供）：联合国艾滋病规划署的统计数据估计，每年约有80万婴儿感染艾滋病毒，其中90%的感染发生在资源有限的环境中。几乎所有的婴儿艾滋病毒感染都是由于母婴传播，这可能发生在怀孕、分娩或母乳喂养期间。如果不进行治疗，艾滋病毒阳性母亲所生的婴儿中约有25%会感染艾滋病毒。在资源丰富的环境中，高效抗逆转录病毒疗法（HAART）治疗已将传播率降至2%以下;然而，确定最佳检测时间和提供早期及时治疗仍然是令人关切的领域。诊断婴儿HIV感染的“金标准”测试是HIV-1 DNA和RNA检测。先前的研究表明，感染婴儿之间检测出阳性感染的时间差异很大。目前的知识是基于主要在美国进行的小型研究。欧洲和最多暴露于单药治疗方案的人群。以前关于母婴传播时机的工作受到一些限制，包括样本量有限和使用临时战略。我们建议的特点检测检测艾滋病毒感染的婴儿和调查的时间MTCT，从几个队列的艾滋病毒暴露的婴儿的数据的综合分析的基础上。我们的建议的核心是形成一个跨学科的合作研究人员从几个队列，包括约5,800艾滋病毒阳性配方奶粉喂养和母乳喂养的婴儿所生的艾滋病毒阳性母亲代表人口在美国，欧洲、非洲和亚洲。由此产生的大型数据库将能够进行统计分析，以评估DNA/RNA检测在不同环境中的性能，包括暴露于HAART的人群和非B亚型感染占主导地位的环境。我们将采用新的统计模型估计的时间MTCT，克服固有的缺点，在以前采用的特设战略。具体而言，我们的提案涉及以下内容：目标1 -HIV-1感染、非母乳喂养婴儿中HIV-1 DNA和RNA检测阳性信号时间分布的表征和比较;目标2a -HIV感染、非母乳喂养婴儿中HIV的MTCT时间估计;以及目标2b -HIV感染、母乳喂养婴儿中HIV的MTCT时间估计。在每一个目标中，将特别强调评价母婴因素，包括母婴抗逆转录病毒治疗的类型、艾滋病毒亚型和分娩方式;母亲的年龄、HIV-1病毒载量和CD 4细胞计数;以及婴儿的CD%和出生体重。从目标2b中收集的结果将作为对母乳喂养为常态的人群中艾滋病毒母婴传播所涉及的风险和因素进行更大的荟萃分析的基础。影响：更好地了解诊断检测的特点和母婴传播的时机，将指导各种战略，以优化对不同人群婴儿的艾滋病毒诊断检测，并将告知安排预防的最佳方法，特别是在资源有限的情况下。 公共卫生相关性：预防艾滋病毒母婴传播是全球遏制艾滋病毒流行努力的基本组成部分。这一奋进的关键挑战包括了解婴儿常用艾滋病毒诊断测试的准确性，以及深入了解艾滋病毒母婴传播的机制和时间。该提案利用深入的统计分析来解决这些问题，其基础是美国几个大型艾滋病毒阳性母亲及其婴儿队列的综合数据，欧洲、非洲和亚洲。