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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要寨卡病毒（ZIKV）可能会流行，并对某些地区的孕妇构成持续威胁人类免疫缺陷病毒（HIV）感染也很常见，这种担忧促使美国国立卫生研究院（NIH）进行研究。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 HIV/ZIKV 合并感染对妊娠的影响妇女及其婴儿。这笔赠款的目的是通过快速从高度获取伴随数据来补充 HIV ZIP。对猕猴的对照研究。具体来说，我们将：目标 1：评估仅感染猴免疫缺陷病毒 (SIV)、仅感染 ZIKV、同时感染 SIV 和 ZIKV、以及既不感染 SIV 也不感染 ZIKV 的恒河猴的不良妊娠结局。感染 SIV 的猕猴将使用抗逆转录病毒药物进行病毒学抑制。所有 24 只怀孕的猕猴都将受到病毒学抑制。在整个妊娠过程中仔细监测不良妊娠结局，包括自发性妊娠流产、长期 ZIKV 病毒血症、SIV 相关疾病和 ZIKV 神经发病机制。目标 2：确定子宫内 SIV 和 ZIKV 感染对婴儿出生第一年生长、听力、视力和神经发育的影响由于猕猴发育比人类快，一岁时发生的异常可能预示着未来的影响。出生时患有先天性寨卡病毒的儿童综合征（CZS）。目标 3：评估 SIV 和 ZIKV 垂直传播的发生率，将对一岁时的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。这项研究是由我们庞大的合作者网络促成的，他们在研究猕猴 SIV 和 ZIKV 方面拥有丰富的经验。这项研究的数据将为 HIV ZIP 提供信息，并提供早期迹象，表明 HIV + 女性所生的婴儿是否面临更高的 CZS 风险。