PHASE III EVALUATION FOLLOWING NEONATAL HSV LIMITED TO THE SKIN, EYE AND MOUTH

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究将评估口服阿昔洛韦长期抑制治疗局限于皮肤、眼睛和口腔（SEM）的HSV感染婴儿的疗效。它将确定口服抑制性阿昔洛韦治疗是否能改善SEM疾病后婴儿的神经系统预后（主要终点）。根据早期CASG研究的数据，选择神经系统预后评估作为主要研究终点，该研究发现，在出生后6个月内，扫描电镜婴儿出现3次皮肤复发与出生后12个月的异常神经系统预后相关。这表明这组婴儿可能发生了中枢神经系统（CNS）内HSV的亚临床再激活。因此，本研究的主要目标是系统地研究抑制性阿昔洛韦，以防止这种假定的亚临床中枢神经系统再激活，从而改善12月龄时的神经系统预后。本研究还将探讨在脑脊液（CSF）其他参数保持正常的情况下，脑脊液（CSF） PCR结果阳性的意义。各组之间将比较随机化后的时间和生命最初12个月内首次脑脊液PCR阳性结果（次要研究终点），结果将与临床神经学评估相关。该研究将确定持续口服阿昔洛韦悬液是否能抑制SEM疾病后婴儿皮肤病变复发（次要研究终点），并将确认长期口服阿昔洛韦治疗SEM疾病婴儿队列的安全性（第三研究终点）。最后，将评估和量化阿昔洛韦抑制性治疗对药物经济学和家庭基础设施问题的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will evaluate the efficacy of long-term suppressive therapy with oral acyclovir in infants with HSV infection limited to the skin, eyes and mouth (SEM). It will determine if suppressive oral acyclovir therapy improves neurologic outcome in infants following SEM disease (Primary Endpoint). Assessment of neurologic outcome was chosen as the primary study endpoint based upon data from an earlier CASG study finding that 3 cutaneous recurrences occurring in SEM infants within the first six months of life correlates with abnormal neurologic outcome when measured at 12 months of life. This suggests that subclinical reactivation of HSV within the central nervous system (CNS) may be occurring with this group of infants. Therefore, systematic study of suppressive acyclovir to prevent this presumed subclinical CNS reactivation and thus to improve neurologic outcome at 12 months of age is the primary goal of this investigation. This study will also address the significance of a positive cerebrospinal fluid (CSF) PCR result when all other CSF parameters remain normal. Comparisons will be made between groups with respect to time post-randomization to first positive cerebrospinal fluid PCR result during the initial 12 months of life (Secondary Study Endpoint), and results will be correlated with clinical neurological assessment. The study will determine if continuous administration of oral acyclovir suspension suppresses recurrent skin lesions in infants following SEM disease (Secondary Study Endpoint), and it will confirm the safety of long-term administration of oral acyclovir therapy in a cohort of infants with SEM disease (Tertiary Study Endpoint). Finally, the effects of suppressive acyclovir therapy on issues of pharmacoeconomic and family infrastructure will be assessed and quantitated.