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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。本研究将评估长期口服阿昔洛韦抑制治疗局限于皮肤、眼睛和口腔的HSV感染婴儿的疗效（SEM）。它将确定抑制性口服阿昔洛韦治疗是否改善SEM疾病后婴儿的神经功能结局（主要终点）。根据早期CASG研究的数据，选择神经系统结局评估作为主要研究终点，该研究发现，出生后前6个月内发生的3例SEM婴儿皮肤复发与出生后12个月时测量的异常神经系统结局相关。这表明中枢神经系统（CNS）内HSV的亚临床再激活可能发生在这组婴儿中。因此，系统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，从而改善神经系统的结果在12个月龄是本调查的主要目标。本研究还将讨论当所有其他CSF参数保持正常时，阳性脑脊液（CSF）PCR结果的意义。将对出生后最初12个月内随机化后至首次脑脊液PCR阳性结果的时间（次要研究终点）进行组间比较，并将结果与临床神经学评估相关。该研究将确定口服阿昔洛韦混悬液连续给药是否能抑制SEM疾病后婴儿的复发性皮肤病变（次要研究终点），并将证实长期口服阿昔洛韦治疗SEM疾病婴儿的安全性（三级研究终点）。最后，将评估和量化抑制性阿昔洛韦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.