Risk factors for early morbidity and mortality of HIV-exposed uninfected infants

暴露于艾滋病毒的未感染婴儿早期发病和死亡的危险因素

• 批准号: 8686729
• 负责人: Scott Dryden-Peterson
• 金额: $ 13.16万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-05 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8686729
• 关键词: 2 year old; Accounting; Acquired Immunodeficiency Syndrome; Address; Affect; Age; Anemia; Antibodies; Biological Factors; Birth; Botswana; Breast Feeding; CD4 Lymphocyte Count; Cells; Cessation of life; Child; Child Mortality; Clinical Data; Country; Data; Development; Development Plans; Disease; Economics; Epidemic; Equilibrium; Etiology; Excess Mortality; Food; Goals; Guidelines; HIV; Health; Highly Active Antiretroviral Therapy; Hospitalization; Household; Humoral Immunities; Immunoglobulin G; Infant; Infant Mortality; Infection; Institutes; Intervention; Knowledge; L Cells; Link; Low Birth Weight Infant; Mediating; Mentors; Meta-Analysis; Morbidity - disease rate; Mothers; Newborn Infant; Outcome; Pattern; Prevention; Public Health; Research; Research Personnel; Resources; Risk; Risk Factors; Specimen; Staging; Time; Vertical Disease Transmission; Viral Load result; Woman; Work; Zidovudine; adverse outcome; antiretroviral therapy; career development; clinically significant; cohort; experience; feeding; high risk; improved; infant outcome; mortality; pathogen; placental transfer; pregnant; premature; prevent; programs; public health relevance; skills; social; transmission process; vaccination strategy

DESCRIPTION (provided by applicant): Over two million children are born to HIV-infected women annually. With advances in access to antiretroviral therapy and strategies to prevent mother-to-child transmission (MTCT), infant infection has become uncommon in settings like Botswana. However, these HIV-exposed but uninfected infants remain at 2 to 4-fold greater risk of dying than matched HIV-unexposed children, accounting for more than half of all deaths before age 5 in Botswana. Despite its great public health importance, the etiology of this mortality gap is unknown and strategies to mitigate this excess mortality in HIV-exposed uninfected (HIV-EU) infants have not been previously studied. Advanced maternal HIV disease is associated with decreased transfer of protective antibodies and poor infant outcomes. Treatment of maternal HIV, through expanded use of maternal highly- active antiretroviral therapy (HAART) for prevention of MTCT, as endorsed by recently revised WHO guidelines, may also improve health outcomes of uninfected infants. However, maternal HAART is associated with increased risk of prematurity, low birth weight, and severe infant anemia- all important predictors of increased mortality. Utilizing unique clinical data and specimens from well-characterized cohorts at the Botswana Harvard AIDS Institute Partnership, the project will examine the critical question of the effect of maternal HAART and other factors on the overall health of HIV-EU infants. The project as two specific aims: 1) determine factors associated with death or hospitalization (including HAART) among 2621 HIV-EU infants in Botswana by pooling data from 4 large cohorts, and 2) determine if reduced infant antibody levels to common pathogens are associated with lack of maternal HAART, and with death or hospitalization in HIV-EU infants. The results of these studies could impact the use of maternal HAART, vaccination strategy, and other interventions to improve outcomes for the rising number of HIV-exposed, uninfected infants. In addition, these mentored projects are part of a detailed Career Development Plan that will provide the Candidate with the knowledge, skills, and experience to successfully transition to an independent investigator. Public Health Relevance Statement (provided by the applicant): Worldwide two million children are born to women with HIV. Most of these infants will not get HIV, but they are still 2-4 times more likely to die by 2 years of age than infants born to mothers without HIV. This project aims to study reasons why this happens with a goal of developing strategies to prevent these deaths.

描述（由申请人提供）：每年，感染艾滋病毒的妇女生育的孩子超过 200 万。随着抗逆转录病毒治疗和预防母婴传播 (MTCT) 策略的进步，婴儿感染在博茨瓦纳等地区已不再常见。然而，这些接触过艾滋病毒但未感染的婴儿的死亡风险仍然是未接触过艾滋病毒的儿童的 2 至 4 倍，占博茨瓦纳 5 岁以下死亡人数的一半以上。尽管其对公共卫生具有重要意义，但这种死亡率差距的病因尚不清楚，并且以前尚未研究过降低暴露于艾滋病毒的未感染婴儿（HIV-EU）婴儿死亡率过高的策略。晚期母亲艾滋病毒疾病与保护性抗体转移减少和婴儿结局不佳有关。正如最近修订的世界卫生组织指南所认可的，通过扩大使用孕产妇高效抗逆转录病毒治疗（HAART）来预防母婴传播，治疗孕产妇艾滋病毒也可能改善未感染婴儿的健康状况。然而，孕产妇HAART与早产、低出生体重和严重婴儿贫血的风险增加有关，这些都是死亡率增加的重要预测因素。该项目将利用来自博茨瓦纳哈佛艾滋病研究所合作伙伴关系的独特临床数据和特征明确的队列样本，研究母亲HAART和其他因素对HIV-EU婴儿整体健康影响的关键问题。该项目有两个具体目标：1) 通过汇集 4 个大型队列的数据，确定博茨瓦纳 2621 名 HIV-EU 婴儿的死亡或住院（包括 HAART）相关因素；2) 确定婴儿针对常见病原体的抗体水平降低是否与母亲缺乏 HAART 以及 HIV-EU 婴儿的死亡或住院有关。这些研究的结果可能会影响孕产妇高效抗逆转录病毒治疗（HAART）、疫苗接种策略和其他干预措施的使用，以改善越来越多的暴露于艾滋病毒的未感染婴儿的结局。此外，这些指导项目是详细职业发展计划的一部分，该计划将为候选人提供成功过渡为独立调查员所需的知识、技能和经验。 公共卫生相关性声明（由申请人提供）：全世界有 200 万儿童是感染艾滋病毒的妇女所生。这些婴儿中的大多数不会感染艾滋病毒，但他们仍然是 2-4 岁 两岁时死亡的可能性比没有感染艾滋病毒的母亲所生的婴儿高出一倍。该项目旨在研究发生这种情况的原因，目的是制定预防这些死亡的策略。