Clinical Research in HSV Infections

描述（由申请人提供）：这个职业中期导师奖的目标是通过与几个正在进行的培训项目合作，扩大华盛顿大学临床病毒学培训，重点是2型单纯疱疹病毒感染。沃尔德博士是一位成功的、资金充足的临床研究者，曾指导过传染病研究员和研究生。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。这两个项目都侧重于严重感染2型单纯疱疹病毒的人群：孕妇和艾滋病毒感染者。第一个项目侧重于预防新生儿单纯疱疹病毒。具体目的是：1)评价单独进行HSV血清学检测与孕妇及其伴侣进行HSV血清学检测对妊娠晚期性行为的影响；2)评价阿昔洛韦治疗预防HSV-2血清阳性产妇分娩时病毒脱落的效果及分娩时给予阿昔洛韦对新生儿的影响；3)开发和测试一种快速PCR检测方法，以检测分娩时女性生殖器HSV的脱落。这种方法预防HSV在怀孕期间结合行为，药理学，和新的诊断工具。第二个项目侧重于1型单纯疱疹病毒与艾滋病毒之间的相互作用。具体目的是：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感染者全身HIV复制的影响；3)确定HAART对HIV感染者HSV再活化的影响。该项目整合了流行病学、临床和实验方法，以了解2型单纯疱疹病毒感染的发病机制、后遗症和预防策略，旨在为具有不同背景的学员提供以患者为导向的临床病毒学监督研究指导。这些人将包括传染病（内科、儿科和妇产科）、医学院学生和住院医生，以及流行病学研究生。该项目建立在一个成功的临床研究基础设施上，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，从而进行转化研究。还提供研究行为道德方面的培训，以及参加有关领域的研讨会、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.