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: 8868893
• 负责人: Scott Dryden-Peterson
• 金额: $ 12.85万
• 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 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8868893
• 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; HIV-exposed uninfected infant; 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; 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.

描述（由申请人提供）：每年有超过200万儿童出生于HIV感染的妇女。随着进入抗逆转录病毒疗法的进步和防止母亲传播（MTCT）的策略，在博茨瓦纳这样的环境中，婴儿感染变得罕见。但是，这些暴露于HIV但未感染的婴儿死亡的风险比匹配的无暴露于艾滋病毒的儿童高2至4倍，占博茨瓦纳5岁之前所有死亡的一半以上。尽管公共健康的重要性非常重要，但这种死亡率差距的病因尚不清楚，并且以前尚未研究过在受HIV暴露的未感染（HIV-EU）婴儿中减轻这种过多死亡率的策略。晚期母亲艾滋病毒疾病与保护性抗体和婴儿预后不良的转移有关。通过扩大母体高度活性抗逆转录病毒疗法（HAART）来预防MTCT的孕产妇HIV的治疗，正如最近修订的WHO指南所认可的那样，也可能会改善未感染婴儿的健康结果。但是，孕产妇Haart与早产，低出生体重和严重的婴儿贫血的风险增加有关 - 所有重要的死亡率预测指标。该项目利用了博茨瓦纳哈佛大学研究所伙伴关系的独特临床数据和标本，该项目将研究产妇Haart和其他因素对HIV-EU婴儿整体健康的影响的关键问题。该项目是两个具体目的：1）确定波茨瓦纳2621名HIV-eu婴儿与死亡或住院（包括HAART）相关的因素，通过汇总4个大型同类群的数据，以及2）确定与常见病原体的降低的婴儿抗体水平是否与缺乏母体HAART以及HIV-EUU婴儿的死亡或住院相关。这些研究的结果可能会影响孕产妇HAART，疫苗接种策略和其他干预措施的使用，以改善艾滋病毒暴露，未感染的婴儿数量增加的结果。此外，这些指导的项目是一项详细的职业发展计划的一部分，该计划将为候选人提供知识，技能和经验，以成功地过渡到独立研究者。