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.

用于预防母亲的3药抗逆转录病毒疗法（ART）的背景实施 HIV的传播（PMTCT）在全球近垂直传播大大降低了。然而，最近的证据表明，艺术女性的死产，早产和小针对胎龄婴儿。尽管不良出生结果的原因尚不清楚，但数量越来越多研究发现，高血压是一个重要的危险因素，导致我们假设孕产妇内皮功能障碍会导致艾滋病毒感染的妇女的不良出生结果。候选人我16年前首次为PMTCT领域做出了贡献，当时我住在南非并跑了第一个局部非政府组织在怀孕中提供抗逆转录病毒预防。我决定从事PMTCT的研究职业在我的传染病奖学金期间，不良的出生结果，出生了很大博茨瓦纳的监视研究发现，不良出生结果和高血压的率极高在控制艾滋病毒良好的妇女中。我正在申请5年K23职业发展奖，该奖关于我的研究金研究结果。 K23奖将提供必要的培训和经验成为一名独立研究者，研究妊娠药物安全，确定基本机制不良的出生结果和测试干预措施，以改善感染HIV的妇女的妊娠结局。指导我的主要导师罗杰·夏皮罗（Roger Shapiro）博士已经进行了临床试验，《童年研究》死亡率和博茨瓦纳（Botswana）的出生成果研究已有15年以上，一直是我的研究导师自居住以来。我们一起确定了一个出色的指导团队，包括Paige Williams博士（A 生物统计学家在怀孕的药物安全研究方面具有专业知识）和Raina Fichorova博士（具有妇产科 20年的经验经营一个具有产科免疫学实验室的经验）。研究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视研究中，我的研究将为1）确定高血压在不良怀孕中的作用结果和2）评估低孕酮和慢性炎症作为不良机制的作用出生结果。我将评估HIV状态，特定艺术方案和/或艺术启动的时机是否影响高血压，孕酮水平和慢性炎症的标志物。这些组合分析是设计较大的纵向队列的关键第一步，以进一步阐明不良出生的机制艾滋病毒感染的妇女的艺术成果。这将导致改善出生结果的干预措施在感染艾滋病毒的妇女中。培训研究目标得到了培训计划的支持，其中包括获得MSC 流行病学，进一步培训不良出生结果的病理生理学以及赠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.

DOI：
10.1016/j.eclinm.2020.100573
发表时间：
2020-11
期刊：
EClinicalMedicine
影响因子：
15.1
作者：
Kanters S;Vitoria M;Zoratti M;Doherty M;Penazzato M;Rangaraj A;Ford N;Thorlund K;Anis PAH;Karim ME;Mofenson L;Zash R;Calmy A;Kredo T;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？