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.

项目总结/摘要 寨卡病毒（ZIKV）可能成为地方性流行病，并对一些地区的孕妇构成持续威胁。 在那里，人类免疫缺陷病毒（HIV）感染也很常见。这种担忧促使NIH 启动“婴儿和妊娠期艾滋病毒和寨卡病毒前瞻性队列研究”（HIV ZIP）--一项为期4-6年、2,000人的国际临床研究，旨在研究艾滋病毒/寨卡病毒合并感染对妊娠的影响。 妇女和她们的婴儿。 该补助金的目的是通过快速获得来自高风险人群的伴随数据来补充HIV ZIP。 对猕猴的对照研究。 具体而言，我们将： 目标1：评价仅感染猴免疫缺陷病毒（SIV）、仅感染ZIKV、SIV和ZIKV两者以及既不感染SIV也不感染ZIKV的恒河猴的不良妊娠结局。就像HIV ZIP试验一样， SIV感染的猕猴将使用抗逆转录病毒药物进行病毒抑制。所有24个怀孕将 在整个妊娠期间仔细监测不良妊娠结局，包括自发性 流产、延长的ZIKV病毒血症、SIV相关疾病和ZIKV神经发病机制。 目的2：确定宫内SIV和ZIKV感染对婴儿出生后第一年的生长、听力、视力和神经发育的影响。由于猕猴比人类发育得更快，一岁时发生的异常可能预示着先天性寨卡儿童的未来影响 CZS综合征。 目的3：评估SIV和ZIKV垂直传播的发生率。将在一岁时对新生儿进行全面尸检，并检查60多个组织是否存在 SIV和ZIKV病毒RNA以及负义ZIKV RNA复制中间体。 这项研究是由我们的合作者谁拥有广泛的经验研究猕猴SIV和ZIKV的大型网络成为可能。这项研究的数据将为HIV ZIP提供信息，并提供HIV+妇女所生婴儿是否有增加CZS风险的早期指标。