Impact of maternal HIV on Mycobacterium tuberculosis infection among peripartum women and their infants

孕产妇HIV感染对围产期妇女及其婴儿结核分枝杆菌感染的影响

• 批准号: 9137077
• 负责人: Sylvia LaCourse
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9137077
• 关键词: Address; Affect; Age-Months; Algorithms; Area; Award; Benefits and Risks; Biological Assay; Centers for Disease Control and Prevention (U.S.); Characteristics; Child; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Clinical Trials Design; Cohort Studies; Communicable Diseases; Complex; Cost Effectiveness Analysis; Crowding; Data; Data Analyses; Data Collection; Development Plans; Diagnostic; Diagnostic tests; Disease; Economic Models; Employment; Enrollment; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Evaluation; Exposure to; Foundations; Funding; Future; Goals; HIV; Household; Hypersensitivity; Immunologics; Incidence; Individual; Infant; Infection; Institution; Interferon Type II; Internal Medicine; International; Intervention; Intervention Trial; Kenya; Lead; Learning; Logistic Regressions; Maternal and Child Health; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; Mothers; Outcome; Paternal Exposure; Pathogenesis; Pediatrics; Performance; Physicians; Pilot Projects; Population; Positioning Attribute; Postpartum Period; Predisposition; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention strategy; Prevention trial; Preventive therapy; Publications; Recording of previous events; Research; Research Personnel; Research Proposals; Research Training; Resources; Risk; Role; Staging; Testing; Time; Training; Tuberculin Test; Tuberculosis; Universities; Washington; Woman; Women' s Health; antiretroviral therapy; base; career; career development; clinically relevant; cofactor; cohort; cost; cost effectiveness; design; diagnostic screening; effectiveness clinical trial; epidemiologic data; evidence base; evidence based guidelines; experience; health economics; health seeking behavior; improved; infant outcome; infectious disease model; instructor; isoniazid; mortality; performance tests; pregnant; programs; prospective; public health relevance; screening; skills; trial design

 DESCRIPTION (provided by applicant): This K23 Mentored Patient-Oriented Research Career Development Award proposal describes a training and research program that will enable the Candidate to achieve her goal of becoming an independent clinical investigator with expertise in HIV/tuberculosis (TB) and maternal and child health. The Candidate is an Infectious Disease physician trained in Internal Medicine and Pediatrics, with experience in evaluating TB diagnostics, and implementation and evaluation of HIV and TB screening algorithms. For this K23 award, the career development plan will provide the Candidate with mentored learning in advanced epidemiologic, biostatistical, and health economics modeling methods while investigating whether maternal HIV is associated with increased risk of Mycobacterium tuberculosis (Mtb) infection in peripartum women and their infants, and if HIV and pregnancy stage influence latent tuberculosis (LTBI) infection test discordance. HIV-infected individuals and infants have an increased risk of progression from Mtb infection to TB disease. Pregnant and postpartum periods have also been associated with increased risk of TB. Whether maternal HIV increases susceptibility to Mtb infection among peripartum women and their infants, and the dual roles of HIV and peripartum stage on latent TB testing are unknown. The investigator proposes to develop new parallel prospective cohorts enrolling HIV-infected and uninfected pregnant women and their infants. Research Specific Aims are to determine the: (Aim 1) effect of maternal HIV on risk and timing of maternal peripartum Mtb infection, (Aim 2) influence of maternal HIV on risk of infant Mtb infection, and (Aim 3) effect of maternal HIV status and peripartum stage on LTBI test performance, including interferon gamma-release assays (IGRA) and tuberculin skin tests (TST). The incidence of maternal Mtb infection will be estimated and compared between HIV-infected and HIV-uninfected pregnant women using IGRA in pregnancy, and at 6 weeks, and 1 year postpartum. The prevalence of Mtb infection in HIV-exposed and HIV-unexposed infants will be compared at 6 and 12 months of age by IGRA. TST and IGRA discordance will be compared in pregnancy, early postpartum, and late postpartum within each maternal cohort and between HIV-infected and uninfected women. Potential cofactors for maternal and infant Mtb infection and maternal LTBI test discordance will be evaluated. The Candidate proposes training designed to provide her skills in implementing prospective cohort studies and conducting complex longitudinal data analysis in maternal-infant cohorts as part of her research proposal, as well as in interventional trial design, cost-effectiveness and outcomes modeling to provide a foundation for future directions including submitting an R01 proposal. Skills will be gained through directed mentorship, didactic coursework, the proposed research plan, as well as additional mentor-identified opportunities to collaborate on international HIV/TB trials. Her specific goals over the training period are to 1) gain proficiency in advanced logistic regression and linear mixed models, 2) develop content expertise in key areas of HIV/TB-related research in maternal child health settings, 3) lead a longitudinal epidemiologic study, 4) contribute to understanding epidemiologic correlates of Mtb infection in HIV-infected mothers and their children, 5) build a foundation in cost-effectiveness modeling including the use of composite risk-benefit maternal-infant outcomes, and 6) generate original data and scientific questions while expanding her publication record in order to successfully compete for independent funding at the R01 level. The Candidate has identified an interdisciplinary team of mentors (Drs. John-Stewart, Gupta, Kinuthia, Richardson) and collaborators (Drs. Horne, Maleche-Obimbo, Cain, Levin) from University of Washington, Johns Hopkins University, University of Nairobi, and CDC with expertise in HIV and TB epidemiology in women and children, longitudinal cohort studies and clinical trials, TB diagnostics, cost-effectiveness and infectious disease modeling. The Candidate's institution has a long-standing history of collaborative research in Kenya. Her mentors and institution have committed the resources needed to successfully advance her research independence. The research findings will provide important data regarding TB epidemiology and pathogenesis, and inform future TB interventional trials and models in the context of maternal/child health. This proposed project will provide the groundwork for the Candidate's career goal to become an independent clinical researcher with a focus on improving the health of women and their children in areas of high HIV/TB burden through evidence- based preventive strategies.

 描述（由申请人提供）： K23 指导性以患者为导向的研究职业发展奖提案描述了一项培训和研究计划，该计划将使候选人能够实现成为一名具有艾滋病毒/结核病 (TB) 和妇幼健康专业知识的独立临床研究者的目标。 候选人是一位接受过内科和儿科培训的传染病医生，具有评估结核病诊断以及艾滋病毒和结核病筛查算法的实施和评估的经验。对于该 K23 奖项，职业发展计划将为候选人提供高级指导学习。流行病学、生物统计学和卫生经济学建模方法，同时调查孕产妇艾滋病毒是否与围产期妇女及其产妇结核分枝杆菌 (Mtb) 感染风险增加有关婴儿，以及 HIV 和妊娠阶段是否影响潜伏性结核病 (LTBI) 感染测试的不一致。 HIV 感染者和婴儿从 Mtb 感染进展为 TB 病的风险增加 怀孕和产后时期也与 TB 风险增加有关。母亲 HIV 是否会增加围产期妇女及其婴儿对 Mtb 感染的易感性。 HIV 和围产期对潜伏性结核病检测的双重作用尚不清楚。 研究人员建议开发新的平行前瞻性队列，招募感染艾滋病毒和未感染艾滋病毒的孕妇及其婴儿，研究具体目标是确定：（目标 1）孕产妇艾滋病毒对孕产妇围产期结核分枝杆菌感染风险和时间的影响，（目标 2）。 ）母亲 HIV 对婴儿 Mtb 感染风险的影响，以及（目标 3）母亲 HIV 状态和围产期阶段对 LTBI 测试表现（包括干扰素 γ 释放）的影响使用 IGRA 测定（IGRA）和结核菌素皮肤试验（TST）将估计并比较 HIV 感染和未感染 HIV 的孕妇在怀孕期间、产后 6 周和产后 1 年的感染率。将通过 IGRA 比较 6 个月和 12 个月大时暴露于 HIV 的婴儿和未暴露于 HIV 的婴儿的 Mtb 感染情况，并比较 IGRA 的不一致性。将评估每个孕产妇队列中的怀孕、产后早期和产后晚期以及感染 HIV 和未感染的妇女之间孕产妇和婴儿 Mtb 感染以及孕产妇 LTBI 测试不一致的潜在辅助因素。 作为其研究提案的一部分，候选人提出了旨在提供其实施前瞻性队列研究和在母婴队列中进行复杂纵向数据分析的技能的培训，以及干预试验设计、成本效益和结果建模的技能，以提供基础未来的方向，包括提交 R01 提案，将通过指导指导、教学课程、拟议的研究计划以及导师确定的国际艾滋病毒/结核病试验合作机会来获得。 她在培训期间的具体目标是 1) 熟练掌握高级逻辑回归和线性混合模型，2) 培养母婴健康环境中艾滋病毒/结核病相关研究关键领域的内容专业知识，3) 领导一项纵向流行病学研究，4) 有助于了解 HIV 感染母亲及其子女 Mtb 感染的流行病学相关性，5) 为成本效益模型奠定基础，包括使用复合风险效益母婴结局， 6) 生成原始数据和科学问题，同时扩大她的发表记录，以便成功竞争 R01 级别的独立资助。候选人已确定一个跨学科导师团队（John-Stewart、Gupta、Kinuthia、Richardson 博士），以及来自华盛顿大学、约翰·霍普金斯大学、内罗毕大学和疾病预防控制中心的合作者（Horne、Maleche-Obimbo、Cain、Levin 博士）在妇女和儿童中的艾滋病毒和结核病流行病学方面拥有专业知识。候选人的机构在肯尼亚有着悠久的合作研究历史，她的导师和机构投入了成功推进其研究独立性所需的资源。 。 研究结果将提供有关结核病流行病学和发病机制的重要数据，并为未来在孕产妇/儿童健康方面的结核病干预试验和模型提供信息。 拟议的项目将为候选人成为一名独立临床研究员的职业目标奠定基础，重点是通过循证预防策略改善艾滋病毒/结核病高负担地区妇女及其子女的健康。