Assessing the impact of acquired immunodeficiency on congenital Zika virus

项目摘要/摘要 寨卡病毒(ZIKV)很可能成为地方性疾病，并对该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。这种担忧促使美国国立卫生研究院 启动“婴儿和妊娠中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、2000人参与的国际临床研究，以考察艾滋病毒/寨卡病毒混合感染对孕妇的影响 妇女和她们的婴儿。 这笔赠款的目的是通过快速从Highly获得伴随数据来补充HIV ZIP 对猕猴的对照研究。 具体来说，我们会： 目的1：评价仅感染猴免疫缺陷病毒(SIV)、仅感染ZIKV、同时感染SIV和ZIKV、不感染SIV和ZIKV的猕猴的不良妊娠结局。就像HIV ZIP试验一样， 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次怀孕都会 在整个妊娠期间仔细监测不良妊娠结局，包括自然妊娠 流产、长期ZIKV病毒血症、SIV相关疾病和ZIKV神经发病。 目的2：明确宫内SIV和ZIKV感染对婴儿出生第一年的生长、听力、视力和神经发育的影响。因为猕猴比人类发育得更快，一岁前出现的异常可能预示着出生时携带先天性寨卡病毒的儿童未来的影响。 综合征(CZS)。 目的3：评估SIV和ZIKV垂直传播的发生率。新生儿的全面尸检将在一岁时进行，并将检查60多个组织是否存在 SIV和ZIKV病毒RNA以及负义ZIKV RNA复制中间产物。 这项研究是由我们庞大的合作者网络实现的，他们对猕猴的SIV和ZIKV都有丰富的研究经验。这项研究的数据将为HIV ZIP提供信息，并提供艾滋病毒+母亲所生婴儿是否有更高的CZS风险的早期指示。

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.