Long-term neurocognitive outcomes of HIV-exposed uninfected children

每年，在撒哈拉以南非洲出生的儿童中有100多万人感染艾滋病毒，但未受感染， 随着抗逆转录病毒疗法（ART）可获得性的改善，艾滋病患者人数将继续增加。长期 子宫内暴露于艾滋病毒和抗逆转录病毒疗法对儿童健康和福祉的影响尚未得到充分研究。 特别是在资源有限的情况下。CHEU感染传染病的风险较高， 研究表明，与没有艾滋病毒的孩子相比，他们的神经认知发育可能受损 exposure.确定神经认知延迟的原因和风险因素对于发展神经认知延迟至关重要。 采取有效干预措施，改善CHEU儿童的生活。该提案利用了独特的 有机会评估宫内HIV和ART暴露对儿童神经认知发育的影响 我们正在马拉维进行一项正在进行的临床研究，我们在筛选 孕妇，登记婴儿和进行密集的新生儿适应性免疫分析， 以下三类婴儿：（1）首次产前检查时被诊断感染艾滋病毒的妇女所生的CHEU， 不受控制的病毒血症至少一半的妊娠;（2）CHEU出生的妇女开始抗逆转录病毒治疗怀孕前 检测不到病毒载量;（3）未感染HIV的母亲所生婴儿。在这一建议中，我们将继续 入组我们的CHEU队列和没有HIV暴露的儿童，以达到所需的样本量， 对神经认知结果进行强有力的纵向分析。我们将适应标准化和本地化 经过验证的评估工具，以调查整体神经发育以及关键的神经认知领域。 在我们达到最初的里程碑后，我们建议在18岁、36岁和60岁时评估神经认知发展 月龄。我们的跨学科研究团队由传染病专家，发育儿科医生， 心理学家和免疫学家将领导一个最全面的研究CHEU在资源有限的 同时解决母体和新生儿因素对神经认知发育的影响 在这个人口。我们假设，在子宫内暴露于HIV将损害神经认知发育的儿童， 艾滋病毒感染母亲在出生后五年内未接受艾滋病毒感染治疗的情况 怀孕将显示出更多的延迟比儿童的母亲与检测不到艾滋病毒载量的整个 怀孕我们进一步假设，出生时的免疫状态将导致神经认知功能受损， 高浓缩铀儿童的发展，并探讨基本的母亲病史或实验室检查可能 找出高危婴儿。这项研究的结果可以立即转化为干预措施， 改善CHEU的生活，特别是在资源匮乏的环境中。

Every year, over a million children HIV-exposed but uninfected (CHEU) are born in sub-Saharan Africa and this population will continue to increase with improving availability of antiretroviral therapy (ART). The long-term effects of in utero exposure to HIV and ART on child health and well-being have not been adequately characterized, especially in resource-limited settings. CHEU are at higher risk for infectious diseases and recent studies suggest they may have impaired neurocognitive development compared to their children without HIV exposure. Identifying the causes of and risk factors for neurocognitive delay is essential for the development of effective interventions to improve the lives of CHEU children. This proposal takes advantage of the unique opportunity to evaluate the impact of in utero HIV and ART exposure on neurocognitive development in children by extending the cohort enrolled in an ongoing clinical study we are conducting in Malawi. We are screening pregnant women, enrolling infants and conducting intensive analysis of neonatal adaptive immunity among infants in three categories: (1) CHEU born to women diagnosed with HIV at the first antenatal visit, thus exposed to uncontrolled viremia for at least half of gestation; (2) CHEU born to women initiated on ART prior to conception with undetectable viral loads; and (3) infants born to HIV uninfected mothers. In this proposal, we will continue enrollment into our cohort of CHEU and children without HIV exposure to reach the sample size required to conduct a robust longitudinal analysis of neurocognitive outcomes. We will adapt standardized and locally validated assessment tools to investigate overall neurodevelopment as well as key neurocognitive domains. After our initial milestones are achieved, we propose to evaluate neurocognitive development at 18, 36, and 60 months of age. Our interdisciplinary study team of infectious disease specialists, developmental pediatricians, psychologists and immunologists will lead one of the most comprehensive studies of CHEU in resource-limited settings to simultaneously address the impact of maternal and neonatal factors on neurocognitive development on this population. We hypothesize that in utero exposure to HIV will impair neurocognitive development in the first five years of life and children born to HIV-infected mothers with untreated HIV infection at the start of pregnancy will demonstrate more delay than children of mothers with undetectable HIV viral load throughout pregnancy. We further hypothesize that immunological status at birth will contribute to impaired neurocognitive development in HEU children and explore the possibility that basic maternal history or laboratory tests may identify the highest risk infants. The results of this study can immediately be translated into interventions to improve the lives of CHEU, especially in low-resource settings.