Clinical Research in HSV Infections

描述（由申请人提供）：这个职业生涯中期导师奖的目标是扩大临床病毒学的培训，重点是HSV-2感染，在华盛顿大学，通过与几个正在进行的培训计划合作。Wald博士是一位成功且资金充足的临床研究人员，曾指导传染病研究员和研究生。拟议的研究是Wald博士正在进行的研究计划中两个主题相关项目的延续。这两个项目的重点是易受HSV-2感染的人群：孕妇和艾滋病毒感染者。第一个项目侧重于预防新生儿HSV。具体目标是：1）评价单纯孕妇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HSV-2血清学阳性孕妇分娩时病毒脱落的有效性以及分娩时给予阿昔洛韦对新生儿的影响; 3）建立并测试一种快速PCR检测方法，以检测分娩时妇女生殖器HSV脱落。这种在怀孕期间预防HSV的方法结合了行为学，药理学和新的诊断工具。第二个项目的重点是HSV-1和艾滋病毒之间的相互作用。具体目标是：1）测量临床和亚临床HSV-2再活化对粘膜HIV复制的影响; 2）确定HSV-2再活化对用HAART治疗和未用HAART治疗的HIV感染患者中的系统性HIV复制的影响; 3）确定HAART对HIV感染者中的HSV再活化的影响。该计划整合了流行病学，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的监督研究指导。其中包括传染病研究员（内科、儿科和妇产科）、医科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，允许进行转化研究。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.