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.

在高艾滋病毒患病率地区，妇女在怀孕和母乳喂养期间患HIV的高风险。保护 妇女并消除了世界卫生组织的母亲到儿童艾滋病毒传播目标 建议向HIV阴性孕妇/产后妇女提供口服预防前预防（PREP） 高负荷设置。迄今为止，尚未对使用产前准备的大规模纵向安全评估 进行了，没有长期数据超过12个月。拟议的研究旨在量化婴儿 准备后产后准备和评估预备后的出生，骨骼，生长和神经认知结果 通过孩子五岁生日接触。我们的总体目标是定义一个全面的安全性 在肯尼亚的独特持续群-RCT中，产前/产后准备比较准备递送方法 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，从9个月扩大到6个月，并在此收集新的结果数据 空前的队列，我们​​在评估婴儿准备的暴露和结果方面处于独特状态。我们的目标： 在子宫内和通过母乳中的瞄准1-量化婴儿准备暴露，通过对母乳的分析 头发样品。将从Prima招收的母亲对收集头发样品以评估准备 通过母乳喂养戒烟在子宫内暴露。头发的准备浓度将使用 经过验证的LC-MS/MS方法。婴儿与母亲毛发浓度的比率（代表程度 孕产妇转移）将被评估。我们还将确定是否使用准备时间，妊娠 预备倡议，生物年龄和婴儿性别的年龄与头发水平和比率有关。 假设：准备在婴儿发毛中可以检测到，并且与母子头发的水平相关。 婴儿准备水平将在出生时达到峰值，并在暴露仅限于母乳时降低。 目标2确定是否与产前预期相关的不良出生和婴儿结果。我们将 比较流产，死产，早产，低出生体重和小胎龄的频率 通过任何产前准备暴露，三个月的暴露和暴露量，婴儿的生长 通过母体准备药物水平。假设：产前准备使用将与不良结果无关。 目标3-评估怀孕和母乳喂养期间的预期暴露是否与婴儿和 长达60个月的儿童骨骼发育，神经认知或成长结果。我们将测量骨矿物 使用双能量X射线绝对模足制，进行神经认知评估并衡量生长的密度 Prima中的母子对延长队列，以检测通过预曝光（二进制和稻草）的差异 准备药物水平）。假设：孕产妇的准备不会导致幼儿结局的变化。 这些高度创新的研究将提供全面的长期结果数据，并具有精确的暴露 迄今为止，妊娠评估中最大的准备的数量。