LABORATORY MARKERS OF IMMINENT CYTOMEGALOVIRUS DISEASE

巨细胞病毒(CMV)是一种常见的感染，由 免疫系统。我可以引起严重疾病的病人 免疫系统被用来防止排斥反应的药物破坏。 移植的器官。在这些移植患者中，检测到的 血液中的CMV(病毒血症)已被证明可以预测 病人会患上疾病。这些信息已经被用来 设计已证明临床受益的对照试验 未发病前巨细胞病毒感染的治疗(称为 先发制人疗法)。在首席调查员的实验室里， CMV(病毒载量)的数量也被证明与 患有巨细胞病毒病。此外，以前确定的风险因素在 三个不同的移植患者群体中的每一个都不再是 一旦病毒载量得到控制，在统计学上具有显著意义。 这些结果表明CMV负荷是主要的决定因素。 并提供了优化使用抗病毒药物的方法 具有抗CMV活性的药物。这项研究项目旨在 适用于艾滋病患者的同一分子病毒学实验室 已在移植中成功评估的技术 病人。患者组相似是因为他们的 免疫受损状态使CMV成为一种常见的 病原体，但它们是不同的，因为受影响的器官范围 是截然不同的。初步结果表明，这些经验教训 研究巨细胞病毒的自然历史和致病机理 移植患者的感染可能会传染给艾滋病患者。 具体地说，我们假设：1)CMV病毒血症将表现为 为即将发生的巨细胞病毒病提供早期标记物。2)患有以下疾病的患者 罹患巨细胞病毒病的病毒血症可能损害了中和能力 抗体活性。3)CMV病毒载量的连续检测 接受治疗的患者将识别那些初始治疗不充分的患者 治疗和那些产生CMV耐药株的人。4)更好 用有效的抗逆转录病毒药物控制艾滋病毒复制可能 加强对CMV活动性感染的免疫控制并预测未来 减少了巨细胞病毒病。总而言之，所有这些结果都将 提高对巨细胞病毒感染及其疾病的认识 病因，将识别出CMV病的高危患者，因此导致 直接用于旨在减少这种疾病的对照临床试验 感染艾滋病毒的患者。

Cytomegalovirus (CMV) is common infection, kept under control by the immune system. I can cause serious disease in patients whose immune systems are damaged by drugs required to prevent rejection of a transplanted organ. In these transplant patients, the detection of CMV in the blood (viremia) has been shown to predict which patients will develop disease. This information has been used to design controlled trials which have demonstrated clinical benefit from treatment of CMV infection before disease has developed (termed pre-emptive therapy). In the laboratory of the Principal Investigator, the quantity of CMV (virus load) has also been shown to correlate with CMV disease. Furthermore, previously identified risk factors in each of 3 distinct populations of transplant patients were no longer significant once virus load had been controlled for statistically. These results demonstrated that CMV load is the major determinant of CMV disease, and provide ways of optimizing the use of antiviral drugs with activity against CMV. This research project aims to apply to AIDS patients the same molecular virologic laboratory techniques which have been successfully evaluated in transplant patients. The patient groups are similar because their immunocompromised state allows CMV to become a common pathogen, but they are different because the range of organs affected is distinct. Preliminary results are presented to show that the lessons learned from studying the natural history and pathogenesis of CMV infection in transplant patients can be transferred to AIDS patients. Specifically, we hypothesize that: 1) CMV viremia will be shown to provide an early marker of imminent CmV disease. 2) Patients with viremia who develop CMV disease may have impaired neutralizing antibody activity. 3) The serial measurement of CMV viral load in patients being treated will identify those with inadequate initial therapy and those who develop resistant strains of CMV. 4) Better control of HIV replication with potent anti-retroviral drugs may improve immune control of active CMV infection and predict future decreases in CMV disease. In combination, all of these results will improve our understanding of CMV infection and the diseases it causes, will identify patients at high risk of CMV disease and so lead directly to controlled clinical trials aimed at reducing that disease in patients with HIV infection.