Assessing the impact of acquired immunodeficiency on congenital Zika virus

评估获得性免疫缺陷对先天性寨卡病毒的影响

• 批准号: 10176384
• 负责人: David H. O'Connor
• 金额: $ 74.74万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-15 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10176384
• 关键词: 1 year old; Affect; Age-Months; Americas; Animals; Anti-Retroviral Agents; Antibody titer measurement; Area; Autopsy; Biological Assay; Birth; Blood; Child; Clinical Research; Clinical Trials; Companions; Complement; Congenital neurologic anomalies; Controlled Study; Cytomegalovirus; Data; Development; Disease; Edema; Epidemic; Female; Fetus; Future; Grant; Growth; HIV; HIV Infections; Hearing; Hepatitis C virus; Human; Human Volunteers; Immune; Immune response; Incidence; Infant; Infant Development; Infection; International; Laboratories; Life; Liquid substance; Macaca; Macaca mulatta; Measurement; Microcephaly; Monitor; Monkeys; Neonatal; Neuraxis; Neuropathogenesis; Newborn Infant; Nucleic Acids; Outcome Measure; Pediatric HIV/AIDS Cohort Study; Persons; Pharmaceutical Preparations; Pregnancy; Pregnant Women; Prospective cohort study; RNA replication; Research Design; Resolution; Risk; SIV; Sampling; Spontaneous abortion; Time; Tissues; United States National Institutes of Health; Urine; Vertical Disease Transmission; Viral Load result; Viral Pathogenesis; Viremia; Virus Diseases; Vision; Woman; ZIKA; ZIKV infection; Zika Virus; acquired immunodeficiency; adverse pregnancy outcome; base; co-infection; cohort; congenital zika syndrome; experience; fetal; in utero; infant outcome; maternal outcome; neonatal death; neonate; neurodevelopment; neutralizing antibody; nonhuman primate; pregnant; primary outcome; prospective; viral RNA; virology

Project Summary/Abstract Zika virus (ZIKV) is likely to become endemic and pose a sustained threat to pregnant women in areas where human immunodeficiency virus (HIV) infection is also common. This concern motivated the NIH to initiate ‘Prospective Cohort Study of HIV and Zika in Infants and Pregnancy’ (HIV ZIP) -- an international, 4-6 year, 2,000 person clinical study to examine the impact of HIV/ZIKV co-infections on pregnant women and their infants. The purpose of this grant is to complement HIV ZIP by rapidly obtaining companion data from highly controlled studies of macaque monkeys. Specifically, we will: Aim 1: Evaluate adverse pregnancy outcomes in rhesus macaques infected with simian immunodeficiency virus (SIV) only, ZIKV only, both SIV and ZIKV, and neither SIV nor ZIKV. As in the HIV ZIP trial, SIV-infected macaques will be virologically suppressed using antiretroviral drugs. All 24 pregnancies will be monitored carefully throughout gestation for adverse pregnancy outcomes including spontaneous miscarriage, prolonged ZIKV viremia, SIV-associated disease, and ZIKV neuropathogenesis. Aim 2: Define impacts of in utero SIV and ZIKV infections on infant growth, hearing, vision, and neurodevelopment in the first year of life. Because macaques develop more quickly than humans, abnormalities that occur by one year of age may presage future impacts in children born with congenital Zika syndrome (CZS). Aim 3: Assess incidence of vertical transmission of SIV and ZIKV. Comprehensive necropsies of newborns will be performed at one year of age and more than 60 tissues will be examined for the presence of SIV and ZIKV viral RNA, as well as negative-sense ZIKV RNA replication intermediates. This study is made possible by our large network of collaborators who have extensive experience studying both SIV and ZIKV in macaques. Data from this study will inform HIV ZIP and provide an early indication of whether babies born to HIV+ women are at enhanced risk for CZS.

项目摘要/摘要 寨卡病毒（Zikv）可能成为地方病，并对孕妇构成持续威胁 人类免疫缺陷病毒（HIV）感染也很常见。这种关注激发了NIH 启动“对婴儿和怀孕的艾滋病毒和寨卡病毒的前瞻性队列研究”（HIV ZIP） - 一项国际，4 - 6年，2,000人临床研究，以研究HIV/ZIKV共同感染对怀孕的影响 妇女及其婴儿。 这笔赠款的目的是通过迅速从高度获取伴侣数据来补充HIV拉链 猕猴的对照研究。 具体来说，我们将： AIM 1：在感染了猿猴免疫缺陷病毒（SIV）（SIV）的恒河猕猴中的不良妊娠结局，仅ZIKV，SIV和ZIKV，SIV和SIV也不是ZIKV。就像在艾滋病毒拉链试验中一样 SIV感染的猕猴将在病毒学上使用抗逆转录病毒药物进行抑制。所有24个怀孕将 在整个妊娠期间都要仔细监测，以获取不良怀孕的结果 流产，长时间的ZIKV病毒血症，SIV相关疾病和ZIKV神经病发生。 AIM 2：定义子宫内部和ZIKV感染对婴儿第一年的婴儿生长，听力，视力和神经发育的影响。由于猕猴的发展速度比人类更快，因此一岁时出现的异常可能会预示先天性寨卡病子的未来影响 综合征（CZS）。 AIM 3：评估SIV和ZIKV垂直传播的发生率。新生儿的综合尸体将在一岁时进行，将检查60多个组织的存在。 SIV和ZIKV病毒RNA，以及负义ZIKV RNA复制中间体。 我们的大型合作者网络使这项研究成为可能，他们在猕猴中具有丰富的研究SIV和ZIKV的经验。这项研究的数据将为艾滋病毒拉链提供信息，并提供早期迹象表明艾滋病毒+妇女出生的婴儿是否有CZS的风险增加。