Clinical Research in HSV Infections

描述（由申请人提供）：该职业生涯中期导师奖的目标是通过与多个正在进行的培训项目合作，扩大华盛顿大学的临床病毒学培训，重点关注 HSV-2 感染。 Wald 博士是一位成功且资金充足的临床研究者，拥有指导传染病研究员和研究生的记录。拟议的研究是沃尔德博士正在进行的研究计划中两个主题相关项目的延续。这两个项目都重点关注受 HSV-2 感染比例过高的人群：孕妇和 HIV 感染者。第一个项目的重点是预防新生儿单纯疱疹病毒。具体目的是： 1) 评估单独孕妇与孕妇及其伴侣的 HSV 血清学检测对妊娠第三个月性行为的影响； 2) 评估阿昔洛韦治疗预防 HSV-2 血清阳性妇女分娩时病毒脱落的功效以及分娩期间给予阿昔洛韦对新生儿的影响； 3) 开发并测试快速 PCR 检测方法，以检测女性分娩时生殖器 HSV 的脱落情况。这种怀孕期间预防 HSV 的方法结合了行为、药理学和新型诊断工具。第二个项目重点研究 HSV-1 和 HIV 之间的相互作用。具体目标是：1）测量临床和亚临床HSV-2再激活对粘膜HIV复制的影响； 2) 确定HSV-2再激活对接受HAART治疗和未接受HAART治疗的HIV感染患者全身性HIV复制的影响； 3) 确定HAART对HIV感染者HSV再激活的影响。该项目整合了流行病学、临床和实验方法，以了解 HSV-2 感染的发病机制、后遗症和预防策略，旨在为具有各种背景的学员提供以患者为导向的临床病毒学方面的监督研究指导。这些人员将包括传染病研究人员（内科、儿科和妇产科）、医学生和住院医生以及流行病学研究生。该计划建立在成功的临床研究基础设施之上，包括临床设施、数据管理、数据分析和生物统计学，以及与实验室科学家的密切合作，以进行转化研究。还提供研究行为道德方面的培训，以及参加相关领域的研讨会、合作者和课程的机会。

DESCRIPTION (provided by applicant): The goal of this mid-career mentor award is to expand training in clinical virology, with focus on HSV-2 infections, at the University of Washington, through collaborations with several ongoing training programs. Dr. Wald is a successful and well-funded clinical investigator with a record of mentoring infectious disease fellows and graduate students. The proposed research is a continuation of two thematically related projects from Dr. Wald's ongoing research program. Both projects focus on populations that suffer disproportionably from HSV-2 infections: Pregnant women and HIV infected persons. The first project focuses on prevention of neonatal HSV. The specific aims are: 1) To evaluate the effect of HSV serologic testing of pregnant women alone versus pregnant women and their partners on sexual behavior in 3rd trimester of pregnancy; 2) To evaluate the efficacy of acyclovir therapy in prevention of viral shedding at delivery among HSV-2 seropositive women and the effect of acyclovir administered during labor on the neonate; 3) To develop and test a rapid PCR assay to detect genital HSV shedding among women at the time of labor. This approach to HSV prevention during pregnancy combines behavioral, pharmacologic, and novel diagnostic tools. The second project focuses on interactions between HSV-1 and HIV. The specific aims are: 1) To measure the effect of clinical and subclinical HSV-2 reactivation on mucosal HIV replication; 2) To determine the effect of HSV-2 reactivation on systemic HIV replication in HIV-infected patients treated with HAART and not treated with HAART; 3) To determine the effect of HAART on HSV reactivation in HIV infected persons. The program integrates epidemiologic, clinical and experimental approaches to understanding the pathogenesis, sequelae and prevention strategies for HSV-2 infection and aims to provide supervised research mentorship in patient-oriented clinical virology to trainees with a variety of backgrounds. These will include fellows in infectious diseases (internal medicine, pediatrics and ob-gyn), medical students and residents, and graduate students in epidemiology. The program is built on a successful clinical research infrastructure that includes clinical facilities, data management, data analysis and biostatistics, and close collaborations with lab-based scientist that allows for translational research. Training in ethics of conduct of research is also provided, as is access to seminars, collaborators and classes in related fields.