HIV Exposed Uninfected Infant Cohort Study

项目总结/摘要 成功实施母婴传播预防方案的国家减少 在过去十年中，围产期艾滋病毒感染从每年50万例增加到15万例。但现在 很明显，这造成了大量的艾滋病毒暴露但未感染的婴儿， (HEU)他们的发病率和死亡率高于未接触艾滋病毒的同龄人。一些 据估计，每年有100多万儿童，或在某些地区所有出生的30%，是高浓缩铀儿童。 然而，几乎所有关于高浓缩铀这些不良临床结果的现有证据都来自于 从不太严格的横断面或回顾性研究中， 报告临床结局的出生队列几乎都是在Option B+合并时代之前 建议所有感染艾滋病毒的孕妇接受抗逆转录病毒疗法（cART）。目前尚不清楚， cART减少了高浓缩铀增加的疾病负担。当前的优势 有证据表明，高浓缩铀儿童的免疫系统与高浓缩铀儿童的免疫系统在根本上不同， 孩子然而，这些差异的临床重要性远不清楚。迄今为止， 这些免疫改变与临床结果相关。HEUICS的目标是 确定高浓缩铀状态、母婴危险因素和婴儿临床 结果。我们还建议调查3个可能的决定因素，改变新生儿和早期 婴儿免疫功能障碍：母体病毒载量、cART暴露类型和持续时间以及胎儿 暴露于母体免疫激活（IA）。我们的总体目标是确定：1）是否有意义 高浓缩铀婴儿在6个月大时的发病率和/或死亡率有所增加， 妊娠期间母亲的cART，与类似的未暴露于HIV的儿童队列相比 (SA1)2）接受cART的孕妇IA程度及其与婴儿临床的关系 结果（SA 2）; 3）IA与早期正常和异常反应的相关性 婴儿细胞免疫系统（SA 3）。我们将招募1500名感染和未感染艾滋病毒的孕妇 并在6个月大时跟踪母婴配对，在此期间， 死亡率最高。母亲IA状态将在最后三个月或 交付.评估的结局为发病率（感染、患病访视、住院频率 和长度）和死亡率。高浓缩铀增加的预测性临床和实验室风险因素 发病率和死亡率。我们将招募130名患有高血压的母亲， 和低水平的IA，并比较与母体IA相关的婴儿先天免疫标志物。 婴儿将被随访至6个月大，以评估其早期婴儿疾病负担。 一个！!

Project Summary/Abstract Successful implementation of mother-to-child-transmission prevention programs has decreased perinatal HIV infections from 500,000 to 150,000 cases per year in the last decade. But it is now evident that this has created a large and expanding number of HIV-exposed but uninfected infants (HEU) who have more morbidity and mortality than their HIV-unexposed (HU) counterparts. Some estimate that over 1 million children per year, or 30% of all births in some areas, are HEU children. However, nearly all of the available evidence of these adverse clinical outcomes for HEU comes from less rigorous cross sectional or retrospective studies, and the few prospectively followed birth cohorts reporting clinical outcomes nearly all date from before the Option B+ era of combined ART (cART) recommended for all HIV-infected pregnant women. It is unknown whether the increased disease burden of HEU has been diminished by cART. The preponderance of current evidence suggests that the immune systems of HEU children differ in fundamental ways from HU children. However, the clinical importance of these differences is far less clear. To date, none of these immune alterations have been correlated with clinical outcome. The goal of HEUICS is to determine the relationship between HEU status, maternal/infant risk factors and infant clinical outcomes. We also propose to investigate 3 plausible determinants of altered neonatal and early infant immune dysfunction: maternal viral load, cART exposure type and duration, and fetal exposure to maternal immune activation (IA). Our overall goals are to determine: 1) if a meaningful increase in morbidity and/or mortality exists among HEU infants by 6 months of age despite maternal cART during pregnancy, compared with a similar cohort of HIV-unexposed children (SA1); 2) the degree of IA among pregnant women on cART and its association with infant clinical outcome (SA2) and; 3) the association of IA with normal and abnormal responses of the early infant cellular immune system (SA3). We will enroll 1500 pregnant women with and without HIV and follow the mother-infant pairs through 6 months of age, the window during which infant mortality rates are highest. Maternal IA status will be determined during the last trimester or at delivery. Outcomes assessed will be morbidity (infections, sick visits, hospitalization frequency and length) and mortality. Predictive clinical and laboratory risk factors of increased HEU morbidity and mortality will be sought. We will enroll a nested subset of 130 mothers with high and low levels of IA and compare infant innate immune makers that correlate with maternal IA. Infants will be followed through 6 months of age to assess their early infant disease burden. 1! !