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

简介（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高级研究员。Slyker博士提出了K01职业发展奖，以获得流行病学和临床研究方面的指导，结合她在免疫学方面的严格背景，将使她能够在分子流行病学方面追求长期的职业生涯，专注于面临艾滋病毒风险的妇女和儿童。在获奖期间，Slyker博士将接受流行病学、生物统计学、临床试验和巨细胞病毒研究方面的培训，导师在这些领域具有相当的专业知识。John-Stewart, Richardson, Boeckh)，他们都致力于提供密集的支持，并拥有丰富的指导经验。随着巨细胞病毒疫苗和治疗方法的不断发展，拟议的研究解决了一个具有高度公共卫生意义的主题，具有重要的潜在意义。该研究计划将为Slyker博士提供在复杂分析、研究设计和巨细胞病毒发病机制方面获得技能的机会。该候选人和研究计划预计将使斯莱克尔博士发展成为一名独立的研究科学家。华盛顿大学将为斯莱克尔博士的职业发展提供一个理想的环境，并提供资源和机会，以促进她的长期成功。此外，Slyker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。

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.