CMV viremia and mortality in hospitalized HIV-infected children

被诊断为晚期感染艾滋病毒的非洲儿童的死亡率往往超过20%，而且 迫切需要新的策略来改善他们的预后。巨细胞病毒感染，以及 血浆CMV病毒载量是加速HIV进展的危险因素。此外，CMV重新激活 在高达三分之一的危重非免疫抑制患者中，并与死亡率有关。CMV病毒血症 可能通过终末期器官疾病，急性肺损伤，加重，导致危重病人预后不良 炎症反应和免疫调节。我们建议在一群儿童中研究CMV病毒血症。 在危重期间被诊断出感染了艾滋病毒。我们的目标是确定CMV病毒血症对 死亡率和住院时间(目标1)、开始抗逆转录病毒治疗的反应(目标2)以及 免疫激活和炎症(目标3)。我们假设CMV病毒血症将影响约50%的儿童，并将 与死亡率、抗逆转录病毒治疗后免疫恢复受损以及免疫活性升高和 发炎。结果将告知在这一人群中进行的CMV抑制的干预性试验是否 有保证，并将通知试验研究设计。 这项研究将使用181名病情严重的肯尼亚人的存档标本和数据进行 参加HAART儿科紧急启动(PUSH)研究的儿童。年，儿童被诊断出感染艾滋病毒。 医院，开始抗逆转录病毒治疗(ART)，随后进行系列血浆和PBMC的纵向治疗 保存超过24周的标本。我们将使用定量聚合酶链式反应来评估CMV DNA水平并确定 CMV病毒血症的患病率和持续时间。将使用多变量回归模型来评估 巨细胞病毒血症与临床结局(病死率或15天内继续住院)的关系 对抗逆转录病毒治疗的反应(HIV病毒载量、CD4%和幼稚T细胞百分比的变化)和免疫学 参数(血浆炎症标志物水平和活化、衰老T细胞百分比的变化) 同时控制为HIV疾病阶段。通过定义CMV病毒血症之间的关系，ART 严重感染艾滋病毒的儿童的反应性炎症和死亡率，我们的研究可能提供 将巨细胞病毒预防试验作为降低本病高死亡率的策略的基本原理 人口。 好了！

African children diagnosed with HIV infection late in disease have a mortality rate often exceeding 20%, and there is an urgent need for novel strategies to improve their prognosis. Cytomegalovirus (CMV) infection, and plasma CMV viral load are risk factors for accelerated HIV progression. Additionally, CMV reactivation occurs in up to a third of critically ill non-immunosuppressed patients, and is associated with mortality. CMV viremia may contribute to poor outcomes in the critically ill through end organ disease, acute lung injury, augmented inflammatory responses, and immunomodulation. We propose to study CMV viremia in a cohort of children diagnosed with HIV infection while critically ill. Our aims are to determine the impact of CMV viremia on mortality and duration of hospitalization (Aim 1), response to antiretroviral therapy initiation (Aim 2), and Immune activation and inflammation (Aim 3). We hypothesize CMV viremia will affect ~50% of children and will be associated with mortality, impaired immunologic recovery post ART, and elevated immune activation and inflammation. Results will inform whether an interventional trial of CMV suppression in this population is warranted, and will inform trial study design. The study will be conducted using archived specimens and data from a cohort of 181 severely ill Kenyan children enrolled in the Pediatric Urgent Start of HAART (PUSH) Study. Children were diagnosed with HIV in hospital, started on antiretroviral therapy (ART), and followed longitudinally with serial plasma and PBMC specimens stored over 24 weeks. We will use quantitative PCR to assess CMV DNA levels and determine the prevalence and duration of CMV viremia. Multivariable regression models will be used to assess the relationship between CMV viremia and clinical outcome (mortality or continued hospitalization at 15 days), response to ART (change in HIV viral load, CD4 percent, and percentage of naïve T cells), and immunologic parameters (levels of plasma inflammatory markers and change in percentage of activated, senescent T cells) while controlling for HIV disease stage. By defining the relationships between CMV viremia, ART response inflammation, and mortality among severely ill HIV-infected children, our study may provide the rationale for a trial of CMV prophylaxis as a strategy to reduce the high mortality rate in this population. !