Decreasing Adverse Birth Outcomes among HIV-infected Women on Antiretroviral Therapy

接受抗逆转录病毒治疗可减少艾滋病毒感染妇女的不良分娩结果

基本信息

批准号：
10202671
负责人：
Rebecca Marie Zash
金额：
$ 16.44万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10202671
关键词：
Anti-Retroviral Agents Antihypertensive Agents Area Biology Birth Botswana CD4 Lymphocyte Count Child Mortality Childhood Chronic Clinical Cohort Studies Communicable Diseases Complex Conceptions Conduct Clinical Trials Data Discipline of obstetrics Endothelium Enrollment Epidemiology Fellowship Functional disorder Funding Future Grant HIV HIV Infections HIV Seronegativity HIV Seropositivity HIV antiretroviral Hypertension Immunologist Immunology Immunosuppression Inflammation Interleukin-10 Interleukin-6 Intervention K-Series Research Career Programs Laboratories Life Link Longitudinal cohort Low Birth Weight Infant Mediating Mediation Mediator of activation protein Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Mother-to-child HIV transmission Nevirapine Opportunistic Infections Outcome Outcomes Research Pathway interactions Pharmaceutical Preparations Placenta Population Positioning Attribute Pre-Eclampsia Pregnancy Pregnancy Outcome Pregnant Women Premature Birth Prevention Prevention therapy Progesterone Program Development Prophylactic treatment Public Health Schools Publications Regimen Research Research Personnel Research Training Residencies Risk Risk Factors Role Running Serology Site Small for Gestational Age Infant South Africa Spontaneous abortion Testing Training Vertical Disease Transmission Woman adverse birth outcomes adverse outcome adverse pregnancy outcome antiretroviral therapy career catalyst cohort data infrastructure design early onset early pregnancy endothelial dysfunction experience fetal high risk immune activation immune function improved infant morbidity/mortality medication safety mortality neonatal outcome novel pediatric human immunodeficiency virus infection pregnancy hypertension prenatal exposure programs reproductive response stillbirth study population success surveillance study transmission process

项目摘要

Background Implementation of 3-drug antiretroviral therapy (ART) for prevention of mother to child transmission of HIV (PMTCT) has dramatically decreased vertical transmission of HIV globally. However, recent evidence suggests that women on ART have exceptionally high risk of stillbirth, preterm delivery and small for gestational age infants. Though reasons for adverse birth outcomes are unknown, a growing number of studies have found that hypertension is an important risk factor, leading us to hypothesize that maternal endothelial dysfunction causes adverse birth outcomes among HIV-infected women on ART. Candidate I first contributed to the field of PMTCT 16 years ago when I lived in South Africa and ran the first local NGO to provide antiretroviral prophylaxis in pregnancy. I decided to pursue a research career in PMTCT and adverse birth outcomes during my Infectious Diseases fellowship, after performing a large birth surveillance study in Botswana that found strikingly high rates of adverse birth outcomes and hypertension among women with well-controlled HIV. I am applying for a 5-year K23 Career Development Award that builds on findings from my fellowship study. A K23 award will provide the necessary training and experience needed to become an independent investigator studying drug safety in pregnancy, identifying mechanisms underlying adverse birth outcomes and testing interventions to improve pregnancy outcomes among HIV-infected women. Mentoring My primary mentor, Dr. Roger Shapiro, has conducted clinical trials, research on childhood mortality, and birth outcomes research in Botswana for more than 15 years and has been my research mentor since residency. Together we have identified an excellent mentoring team including Dr. Paige Williams (a biostatistician with expertise in studies of drug safety in pregnancy) and Dr. Raina Fichorova (an OB/GYN with 20 years experience running a lab in obstetric immunology). Research Using data collected in an ongoing large birth surveillance study in Botswana, and creating a nested cohort within this surveillance study, my study will 1) establish the role of hypertension in adverse pregnancy outcomes and 2) evaluate the role of low progesterone and chronic inflammation as mechanisms of adverse birth outcomes. I will evaluate whether HIV-status, specific ART regimens and/or the timing of ART initiation influence hypertension, progesterone level and markers of chronic inflammation. These combined analyses are critical first steps in the design of a larger longitudinal cohort to further elucidate mechanisms of adverse birth outcomes among HIV-infected women on ART. This will lead to interventions to improve birth outcomes among HIV-infected women. Training The research objectives are supported by a training plan that includes obtaining an MSc in Epidemiology, further training in the pathophysiology of adverse birth outcomes and a grant support and development program through Harvard Catalyst.

背景实施 3 种药物抗逆转录病毒治疗（ART）以预防母婴传播艾滋病毒传播（PMTCT）极大地减少了全球艾滋病毒的垂直传播。然而，最近的证据表明，接受 ART 的女性死产、早产和流产的风险异常高。小于胎龄儿。尽管不良分娩结果的原因尚不清楚，但越来越多的人的研究发现高血压是一个重要的危险因素，这使我们推测母亲内皮功能障碍导致接受 ART 的 HIV 感染妇女出现不良分娩结局。候选人 16 年前，我第一次为 PMTCT 领域做出贡献，当时我住在南非，并运行了第一个项目当地非政府组织在怀孕期间提供抗逆转录病毒预防。我决定从事 PMTCT 的研究工作以及在我的传染病研究期间进行大分娩后的不良分娩结果博茨瓦纳的监测研究发现不良出生结局和高血压的发生率惊人地高艾滋病毒得到良好控制的女性。我正在申请为期 5 年的 K23 职业发展奖，该奖旨在建立根据我的奖学金研究的结果。 K23 奖项将提供必要的培训和所需的经验成为一名独立研究者，研究妊娠期药物安全性，确定潜在机制不良出生结局和测试干预措施以改善艾滋病毒感染妇女的妊娠结局。指导我的主要导师 Roger Shapiro 博士对儿童进行了临床试验和研究在博茨瓦纳从事死亡率和出生结果研究超过 15 年，一直是我的研究导师自从居住以来。我们共同组建了一支优秀的指导团队，其中包括 Paige Williams 博士（具有妊娠期药物安全性研究专业知识的生物统计学家）和 Raina Fichorova 博士（一位具有妊娠期药物安全性研究经验的妇产科医生） 20 年运行产科免疫学实验室的经验）。研究使用在博茨瓦纳正在进行的大型出生监测研究中收集的数据，并创建一个嵌套的在这项监测研究中，我的研究将 1) 确定高血压在不良妊娠中的作用 2) 评估低孕酮和慢性炎症作为不良反应机制的作用出生结果。我将评估 HIV 状况、特定 ART 治疗方案和/或 ART 开始时间影响高血压、黄体酮水平和慢性炎症标志物。这些综合分析是设计更大的纵向队列以进一步阐明不良分娩机制的关键第一步艾滋病毒感染妇女接受抗逆转录病毒疗法的结果。这将导致采取干预措施来改善出生结果感染艾滋病毒的妇女中。培训研究目标由培训计划支持，其中包括获得以下领域的硕士学位：流行病学、不良分娩结果病理生理学的进一步培训以及拨款支持和通过哈佛催化剂开发计划。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparative efficacy, tolerability and safety of dolutegravir and efavirenz 400mg among antiretroviral therapies for first-line HIV treatment: A systematic literature review and network meta-analysis.

多替拉韦和依非韦伦 400mg 一线 HIV 抗逆转录病毒疗法的疗效、耐受性和安全性比较：系统文献综述和网络荟萃分析。

DOI：
发表时间：
2020-11
期刊：
影响因子：
15.1
作者：
Kanters, Steve;Vitoria, Marco;Zoratti, Michael;Doherty, Meg;Penazzato, Martina;Rangaraj, Ajay;Ford, Nathan;Thorlund, Kristian;Anis, Prof Aslam H;Karim, Mohammad Ehsanul;Mofenson, Lynne;Zash, Rebecca;Calmy, Alexandra;Kredo, Tamara;Bansback, N
通讯作者：
Bansback, N

What will it take to refute the possible safety signal for dolutegravir and neural tube defects?

如何反驳多替拉韦和神经管缺陷可能存在的安全信号？