Optimizing repeat HIV testing during pregnancy and postpartum for PMTCT

优化孕期和产后艾滋病毒重复检测以预防母婴传播

• 批准号: 8992057
• 负责人: Alison L Drake
• 金额: $ 12.64万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-10 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992057
• 关键词: AIDS prevention; Achievement; Acute; Address; Advocate; Africa South of the Sahara; Award; Biological; Breast Feeding; Caring; Characteristics; Child; Chronic; Clinic; Clinical Research; Collaborations; Communicable Diseases; Cost Effectiveness Analysis; Cost of Illness; Coupled; Data; Detection; Disease Progression; Effectiveness; Environment; Epidemiologic Studies; Epidemiology; Evidence based intervention; Future; Goals; Guidelines; HIV; HIV Infections; HIV risk; Heterosexuals; High Risk Woman; Human immunodeficiency virus test; Immunization; Incidence; Individual; Infant; Infection; Interdisciplinary Study; Kenya; Knowledge; Lead; Link; Literature; Logistic Regressions; Maternal and Child Health; Mentored Research Scientist Development Award; Mentors; Mentorship; Methodology; Modeling; Mothers; Pharmaceutical Preparations; Pilot Projects; Policies; Positioning Attribute; Postpartum Period; Postpartum Women; Predisposition; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention approach; Prevention strategy; Process; Public Health; Publications; Reproductive Health; Research; Research Personnel; Resources; Risk; Site; Testing; Time; Time and Motion Studies; Training; Universities; Validation; Visit; Washington; Woman; antiretroviral therapy; base; career; cohort; cost; cost effective; cost effectiveness; data exchange; design; experience; frontier; high risk; implementation science; improved; intervention program; mathematical model; meetings; pregnant; programs; public health relevance; scale up; skills; transmission process

 DESCRIPTION (provided by applicant): The K01 Mentored Research Scientist Development Award will provide the Candidate with the protected time to develop skills in implementation science, mathematical modeling of infectious diseases, and cost- effectiveness analysis, and use these skills in combination with robust epidemiological methodology to become an independent investigator focused on programmatic and public health approaches to HIV prevention for women. The Candidate's long-term objective is to become a global leader in HIV prevention and reproductive health, using implementation science and mathematical modeling to prioritize, design, implement, and evaluate evidence-based interventions, which will help transform public health programs, and guide policy. The proposed 5-year training plan will support the achievement of these objectives with the assistance of the outstanding, interdisciplinary research environment at the University of Washington (UW) and the Kenya Research Program, experienced mentors and advisors, and long-standing collaborations with Kenyan investigators. The training plan was carefully developed with the K01 mentors to include didactic coursework, mentored training, and scientific meetings to fill a gap in the Candidate's training, which will help her develop a unique combination of skills and experience. The mixture of formal training along with a two-tiered approach to mentorship, which includes two co-mentors and a mentoring team, were strategically designed to complete the research and career objectives during the award period and prepare the Candidate for an independent research career. The career goals to be achieved during the award period are: 1) gain knowledge and skills in implementation science and translational clinical research for HIV prevention; 2) develop skills in the construction and validation of mathematical models of infectious diseases to determine program and intervention impacts; 3) obtain practical skills in the conduct of costing and cost-effectiveness analysis, from programmatic and societal perspectives; 4) build the Candidate's research portfolio and publication record, generate data and scientific questions for a future R01, and transition the Candidate into an independent academic career. Research Plan: Risk of HIV acquisition during pregnancy and postpartum is high in sub-Saharan Africa. While current prevention of mother-to-child HIV transmission (PMTCT) programs are designed to detect and treat women with chronic HIV infections, women who miss antenatal HIV testing, are in the process of seroconverting, or who acquire HIV after initial testing have infections that go undetected. Mother-to-child HIV transmission (MTCT) risk is substantially higher among women with acute infection than chronic infection. As PMTCT coverage expands and women with chronic HIV receive triple-drug antiretroviral therapy (ART), an increasing proportion of HIV infected infants will be due to undetected acute maternal HIV, making this an important frontier to address in elimination of MTCT (eMTCT) efforts. In this proposal, we aim to identify the optimal time(s) to conduct repeat maternal HIV testing for PMTCT. The specific aims of the study are to: 1) determine the prevalence of incident or undiagnosed HIV infections among pregnant and postpartum women; 2) model the number of MTCT cases averted by conducting repeat HIV testing using a cohort decision-analytic MTCT model; 3) estimate the incremental costs and cost- effectiveness per case of infant HIV infection averted of repeat testing under different repeat testing strategies compared to no repeat testing. To conduct this study, we will test 4650 women, 930 at each time-point: 3rd trimester (if previously tested HIV negative during pregnancy); delivery; 6 weeks, 6 months, and 9 months postpartum. We will use the prevalence estimates of incident and undiagnosed maternal HIV infection from Aim 1, programmatic PMTCT data at study sites, and the scientific literature to construct and parameterize a cohort decision-analytic MTCT model and determine the number of infant HIV infections that could be averted by implementing this retesting strategy or strategies. We will build upon the MTCT model developed for Aim 2 and use costing data to evaluate cost-effectiveness for Aim 3. Pilot data generated from this study will be used to develop a future, large-scale implementation science study of optimal HIV repeat testing strategy/strategies for PMTCT and can also be leveraged for future HIV prevention studies (i.e., impact on heterosexual transmission, PMTCT in future pregnancies, and maternal HIV disease progression).

 描述(由申请者提供)：K01指导研究科学家发展奖将为候选人提供有保障的时间来发展实施科学、传染病数学建模和成本效益分析方面的技能，并将这些技能与强有力的流行病学方法结合起来，成为一名独立的调查员，专注于为妇女预防艾滋病毒的规划和公共卫生方法。这位候选人的长期目标是成为艾滋病毒预防和生殖健康领域的全球领导者，利用实施科学和数学建模来优先考虑、设计、实施和评估循证干预措施，这将有助于转变公共卫生项目并指导政策。拟议的5年培训计划将在华盛顿大学杰出的跨学科研究环境和肯尼亚研究计划、经验丰富的导师和顾问以及与肯尼亚调查人员的长期合作的帮助下，支持这些目标的实现。培训计划是与K01导师一起精心制定的，包括教学课程、指导培训和科学会议，以填补候选人培训中的空白，这将帮助她发展独特的技能和经验组合。正式培训与包括两名共同导师和一个指导团队在内的两级指导方法相结合，旨在战略性地设计，以完成颁奖期间的研究和职业目标，并为候选人的独立研究生涯做好准备。获奖期间要达到的职业目标是：1)获得艾滋病毒预防实施科学和转化临床研究方面的知识和技能；2)培养构建和验证传染病数学模型的技能，以确定计划和干预措施的影响；3)从计划和社会角度获得进行成本计算和成本效益分析的实用技能；4)建立候选人的研究组合和出版记录，为未来的R01生成数据和科学问题，并将候选人过渡到独立的学术生涯。研究计划：在撒哈拉以南非洲，孕期和产后感染艾滋病毒的风险很高。虽然目前的预防母婴艾滋病毒传播(PMTCT)方案旨在检测和治疗患有慢性艾滋病毒感染的妇女，但错过产前艾滋病毒检测、处于血清转换过程中或在初步检测后感染艾滋病毒的妇女有未被检测到的感染。在患有急性感染的妇女中，母婴传播艾滋病毒(MTCT)的风险比慢性感染高得多。随着母婴传播覆盖范围的扩大和慢性艾滋病毒感染者接受三联药物抗逆转录病毒疗法(ART)，越来越多的艾滋病毒感染婴儿将是由于未被发现的急性产妇艾滋病毒，这使这成为消除母婴传播(EMTCT)努力的一个重要前沿。在这项建议中，我们的目标是确定对预防母婴传播进行重复母体艾滋病毒检测的最佳时间(S)。这项研究的具体目的是：1)确定孕妇和产后妇女中艾滋病毒感染的发病率或未诊断的感染率；2)使用队列决策分析MTCT模型对通过进行重复艾滋病毒检测而避免的母婴传播病例数量进行建模；3)估计在不同重复检测策略下避免重复检测的婴儿艾滋病毒感染病例的增量成本和成本效益。为了进行这项研究，我们将对4650名妇女进行测试，每个时间点都有930名妇女：怀孕第三个月(如果之前在怀孕期间检测出艾滋病毒阴性)；分娩；产后6周、6个月和9个月。我们将使用来自目标1的事件和未诊断的母亲艾滋病毒感染的流行率估计，研究地点的程序性预防母婴传播数据，以及科学文献来构建和参数化队列决策分析的母婴传播模型，并确定通过实施这种重新检测战略可以避免的婴儿艾滋病毒感染的数量。我们将建立在为目标2开发的母婴传播模型的基础上，并使用成本计算数据来评估目标3的成本效益。这项研究产生的试点数据将用于制定未来大规模实施科学研究，以确定预防母婴传播的最佳艾滋病毒重复检测战略/战略，并可用于未来的艾滋病毒预防研究(即对异性传播的影响、预防母婴传播的影响，以及母体艾滋病毒疾病进展)。