权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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）预防母婴感染

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？