Evaluating Infant PrEP Exposure During Pregnancy and Breastfeeding

评估怀孕和母乳喂养期间婴儿 PrEP 暴露

• 批准号: 10436299
• 负责人: Jillian Pintye
• 金额: $ 65.73万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436299
• 关键词: Acute; Adherence; Advocate; Africa; African; Biological Markers; Birth; Blood; Bone Density; Bone Development; Bone Growth; Breast Feeding; Child; Clinical; Data; Dose; Drug Exposure; Drug Kinetics; Dual-Energy X-Ray Absorptiometry; Enrollment; Evaluation; Exposure to; Frequencies; Future; Gestational Age; Goals; Growth; Guidelines; HIV; HIV Infections; HIV Seronegativity; HIV Seropositivity; Hair; High Risk Woman; Human Milk; Infant; Infrastructure; Kenya; Lactation; Liquid Chromatography; Maternal Age; Maternal Exposure; Measures; Metabolism; Methods; Mother-to-child HIV transmission; Mothers; Neurocognitive; Oral; Outcome; Pharmaceutical Preparations; Positioning Attribute; Postpartum Period; Postpartum Women; Pregnancy; Pregnant Women; Premature Birth; Prevalence; Risk; Safety; Sample Size; Sampling; Small for Gestational Age Infant; Spontaneous abortion; Spottings; Tenofovir; Woman; Work; World Health Organization; adverse outcome; antenatal care; antiretroviral therapy; base; cohort; early childhood; expectation; fetal; follow-up; in utero; infant monitoring; infant outcome; innovation; novel; placental transfer; postnatal; pre-exposure prophylaxis; pregnant; prenatal; prenatal exposure; sex; stillbirth; tandem mass spectrometry

In high HIV prevalence regions, women are at high risk for HIV during pregnancy and breastfeeding. To protect women and reach elimination of mother-to-child HIV transmissions targets, the World Health Organization recommends offering oral pre-exposure prophylaxis (PrEP) to HIV-negative pregnant/postpartum women in high-burden settings. To date, no large-scale longitudinal safety evaluation of prenatal PrEP use has been conducted and there are no long-term data beyond 12 months. The proposed study aims to quantify infant pre- and postnatal PrEP exposure and evaluate birth, bone, growth, and neurocognitive outcomes following PrEP exposure through the child’s 5th birthday. Our overall goal is to define a comprehensive safety profile of prenatal/postpartum PrEP in a unique ongoing cluster-RCT in Kenya that compares PrEP delivery approaches in >4500 pregnant women (PrIMA Study, R01AI125498, MPI: John-Stewart/Baeten). By leveraging existing PrIMA infrastructure, extending follow up from 9 to 60 months, and collecting new outcome data in this unprecedented cohort, we are uniquely positioned to assess infant PrEP exposure and outcomes. Our aims: Aim 1-Quantify infant PrEP exposure in utero and via breastmilk through a paired analysis of mother-infant hair samples. Hair samples will be collected from mother-infant pairs enrolled in PrIMA to assess PrEP exposure in utero through breastfeeding cessation. PrEP concentrations in hair will be quantified using validated LC-MS/MS methods. Ratios of infant-to-maternal hair concentrations of PrEP (representing degree of maternal-to-infant transfer) will be assessed. We will also determine whether duration of PrEP use, gestational age at PrEP initiation, maternal age, and infant sex are associated with hair levels and ratios. Hypothesis: PrEP will be detectable in infant hair at delivery and will correlate with levels in maternal hair. Infant PrEP levels will peak at birth and decrease when exposure is limited to breastmilk. Aim 2–Determine whether prenatal PrEP exposure is associated adverse birth and infant outcomes. We will compare frequency of miscarriage, stillbirth, preterm birth, low birth birthweight, and small-for-gestational age, and infant growth by any prenatal PrEP exposure, trimester of exposure, and quantity of exposure measured by maternal PrEP drug levels. Hypothesis: Prenatal PrEP use will not be associated with adverse outcomes. Aim 3–Evaluate whether PrEP exposure during pregnancy and breastfeeding is associated with infant and child bone development, neurocognitive, or growth outcomes up to 60 months. We will measure bone mineral density using dual energy x-ray absorptiometry, conduct neurocognitive assessments, and measure growth in an extension cohort of mother-infant pairs in PrIMA to detect differences by PrEP exposure (binary and strata of PrEP drug levels). Hypothesis: Maternal PrEP will not result in changes in early childhood outcomes. These highly innovative studies will provide comprehensive, long-term outcome data, with precise exposure quantification in the largest PrEP in pregnancy evaluation to date.

在艾滋病毒高流行地区，妇女在怀孕和哺乳期间感染艾滋病毒的风险很高。保护 妇女和实现消除艾滋病毒母婴传播的目标，世界卫生组织 建议向艾滋病毒阴性的孕妇/产后妇女提供口服暴露前预防（PrEP）， 高负荷环境。到目前为止，尚未对产前PrEP使用进行大规模纵向安全性评价。 没有超过12个月的长期数据。这项研究旨在量化婴儿出生前 和出生后PrEP暴露，并评估PrEP后的出生，骨骼，生长和神经认知结果 在孩子的五岁生日时暴露。我们的总体目标是确定一个全面的安全性概况， 产前/产后PrEP在一个独特的正在进行的集群随机对照试验在肯尼亚，比较PrEP交付方法 在> 4500名孕妇中（PrIMA研究，R01AI125498，MPI：John-Stewart/Baeten）。通过利用现有 PrIMA基础设施，将随访时间从9个月延长至60个月，并在此期间收集新的结局数据 前所未有的队列，我们处于独特的地位，以评估婴儿PrEP暴露和结果。我们的目标： 目的1-通过母婴配对分析量化婴儿在子宫内和通过母乳暴露的PrEP 头发样本将从参加PrIMA的母婴对中收集头发样本，以评估PrEP 通过停止母乳喂养在子宫内暴露。头发中的PrEP浓度将使用 经验证的LC-MS/MS方法。婴儿与母亲头发中PrEP浓度的比值（代表 母亲对婴儿的转移）将进行评估。我们还将确定是否持续使用PrEP，妊娠 PrEP开始时的年龄，母亲年龄和婴儿性别与头发水平和比例相关。 假设：PrEP将在分娩时在婴儿头发中检测到，并与母体头发中的水平相关。 婴儿PrEP水平将在出生时达到峰值，当接触仅限于母乳时会下降。 目的2-确定产前PrEP暴露是否与不良出生和婴儿结局相关。我们将 比较流产、死产、早产、低出生体重和小于胎龄儿的频率， 和婴儿生长的任何产前PrEP暴露，暴露的三个月，和暴露量测量 孕妇的PrEP药物水平。假设：产前PrEP使用与不良结局无关。 目的3-评估妊娠和哺乳期间暴露于PrEP是否与婴儿和 儿童骨骼发育，神经认知或生长结果长达60个月。我们将测量骨矿物质 密度使用双能X射线吸收法，进行神经认知评估，并测量生长， PrIMA中母婴对的扩展队列，以检测PrEP暴露的差异（二元和分层 PrEP药物水平）。假设：母体PrEP不会导致儿童早期结局的变化。 这些高度创新的研究将提供全面、长期的结果数据， 迄今为止最大的PrEP妊娠评估中的定量。