Vertical CMV transmission in the setting of maternal HIV-1 infection in Kenya

肯尼亚孕产妇 HIV-1 感染情况下 CMV 垂直传播

• 批准号: 8488400
• 负责人: Jennifer Ann Slyker
• 金额: $ 12.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8488400
• 关键词: Address; Africa South of the Sahara; Antiviral Therapy; Area; Award; Biometry; Blood; Breast Feeding; Child; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Collaborations; Commit; Communicable Diseases; Complement; Complex; Containment; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Data; Databases; Detection; Development; Development Plans; Diagnosis; Doctor of Philosophy; Epidemiologic Studies; Epidemiology; Fostering; Foundations; Future; Genital system; HIV; HIV-1; Health; Highly Active Antiretroviral Therapy; Human Milk; Hypersensitivity; Immune; Immunologics; Immunology; Immunosuppression; Infant; Infection; Intervention; K-Series Research Career Programs; Kenya; Life; Measures; Mentored Research Scientist Development Award; Mentors; Mentorship; Molecular Epidemiology; Morbidity - disease rate; Pathogenesis; Pharmaceutical Preparations; Placebos; Plasma; Pregnancy; Prevention; Production; Public Health; Randomized; Randomized Controlled Trials; Research; Research Design; Resources; Risk; Risk Factors; Role; Scientist; Specimen; Spottings; Swab; Time; Time Factors; Toxic effect; Training; Universities; Vertical Disease Transmission; Viral Load result; Washington; Woman; Zidovudine; antiretroviral therapy; career; career development; design; experience; feeding; improved; infant morbidity/mortality; mortality; novel; pathogen; pediatrician; pregnant; prevent; programs; protocol development; public health relevance; reconstitution; research study; skills; success; therapy design; transmission process; two-arm study; valacyclovir; virology

DESCRIPTION (provided by applicant): Candidate: Dr. Jennifer Slyker, PhD, is a Senior Fellow in the Division of Allergy and Infectious Diseases at the University of Washington. Dr. Slyker proposes a K01 Career Development Award to gain mentorship in epidemiology and clinical research which, combined with her rigorous background in immunology, will enable her to pursue a long-term career in molecular epidemiology focusing on women and children at risk for HIV. During the award period, Dr. Slyker will receive training in epidemiology, biostatistics, clinical trials, and CMV research by mentors with considerable expertise in these areas (Drs. John-Stewart, Richardson, Boeckh), all of whom are committed to provide intensive support and have extensive mentorship experience. The proposed research addresses a topic of high public health significance with important potential implications as CMV vaccines and treatments continue to evolve. The research plan will foster opportunities for Dr. Slyker to gain skills in complex analyses, study design and CMV pathogenesis. The candidate and research plan is anticipated to result in Dr. Slyker's development into an independent research scientist. The UW will provide an ideal milieu for Dr. Slyker's career development with access to resources and opportunities that will foster her long-term success. In addition, Dr. Slyker's continued collaboration with Kenyan pediatrician scientists will provide a context for the design of relevant future studies. Research: There is evidence that cytomegalovirus (CMV) infection contributes significantly to morbidity and mortality in HIV-1 infected infants. Several new advances offer hope for improved diagnosis, treatment and prevention of CMV in resource-limited settings. These include CMV diagnosis from dried blood spots, novel anti-CMV drugs with reduced toxicity, and progress toward the development of a CMV vaccine. For this K-application Dr. Slyker will conduct research using a repository of data and specimens from 3 Kenyan randomized controlled trials comprising HIV-infected women and their infants. CMV viral loads will be measured from stored specimens from the three trials. The aims of the study are 1) To determine the influence of breastfeeding on infant CMV acquisition. Time to CMV will be compared between infants randomized to breastfeeding versus formula feeding. 2) To evaluate the impact of maternal HAART on breast milk CMV viral load and vertical CMV transmission. Breast milk CMV viral loads will be compared at serial time-points during the first year post-partum between HIV-infected women randomized to ZDV/NVP versus HAART. 3) To evaluate the efficacy of maternal valacyclovir therapy during pregnancy and breastfeeding to reduce maternal CMV replication and CMV transmission. Time to CMV will be compared between infants born to HIV-infected women randomized to valacyclovir versus placebo. This complement of studies will provide important new data on the epidemiology of CMV in the setting of HIV-1 and will form a foundation for new interventions that may decrease infant morbidity and mortality.

描述（由申请人提供）： 候选人：Jennifer Slyker 博士，博士，华盛顿大学过敏和传染病部门的高级研究员。 Slyker 博士提议颁发 K01 职业发展奖，以获得流行病学和临床研究方面的指导，再加上她在免疫学方面的严格背景，将使她能够在分子流行病学领域从事长期职业，重点关注有艾滋病毒风险的妇女和儿童。在颁奖期间，Slyker 博士将接受流行病学、生物统计学、临床试验和 CMV 研究方面的培训，导师是在这些领域拥有丰富专业知识的导师（John-Stewart、Richardson、Boeckh 博士），他们都致力于提供深入的培训支持并拥有丰富的指导经验。拟议的研究涉及一个具有高度公共卫生意义的主题，随着巨细胞病毒疫苗和治疗方法的不断发展，具有重要的潜在影响。该研究计划将为 Slyker 博士提供获得复杂分析、研究设计和 CMV 发病机制方面技能的机会。候选人和研究计划预计将使斯莱克博士发展成为一名独立研究科学家。华盛顿大学将为斯莱克博士的职业发展提供理想的环境，让她获得资源和机会，从而促进她的长期成功。此外，斯莱克博士与肯尼亚儿科科学家的持续合作将为未来相关研究的设计提供背景。 研究：有证据表明巨细胞病毒 (CMV) 感染对 HIV-1 感染婴儿的发病率和死亡率有显着影响。一些新进展为在资源有限的环境中改善巨细胞病毒的诊断、治疗和预防带来了希望。其中包括从干血斑中诊断 CMV、毒性降低的新型抗 CMV 药物以及 CMV 疫苗的开发进展。对于这项 K 申请，Slyker 博士将使用来自 3 项肯尼亚随机对照试验的数据和样本库进行研究，其中包括艾滋病毒感染妇女及其婴儿。 CMV 病毒载量将从三项试验中保存的样本中测量。该研究的目的是 1) 确定母乳喂养对婴儿 CMV 获取的影响。将比较随机接受母乳喂养和配方奶喂养的婴儿的 CMV 时间。 2) 评估母亲HAART对母乳CMV病毒载量和CMV垂直传播的影响。将在产后第一年的连续时间点对随机接受 ZDV/NVP 与 HAART 的 HIV 感染妇女之间的母乳 CMV 病毒载量进行比较。 3) 评价妊娠期和哺乳期母亲伐昔洛韦治疗减少母亲CMV复制和CMV传播的功效。将比较随机接受伐昔洛韦组和安慰剂组的 HIV 感染妇女所生婴儿的 CMV 时间。这些补充研究将为 HIV-1 背景下 CMV 流行病学提供重要的新数据，并将为可能降低婴儿发病率和死亡率的新干预措施奠定基础。