Predictors of Immunologic Long-term Non-Progression in Children with HIV

描述(申请人提供)：这项拟议的研究将评估参加预测研究(CIPRA 1U19AI53741-01A1，一项开放标签的随机研究)的儿童T和B淋巴细胞、自然杀伤细胞和单核细胞的激活和其他表面标志，以比较CD4+在15-24%之间时的抗逆转录病毒治疗启动(ART)与CD4+降至15%以下时的抗逆转录病毒治疗启动(ART)。 用流式细胞仪检测300名儿童的CDS、CD4、CDS、CD19、CD16/56、CD4/45RA/62L、CD8/45RA/62L、CD8/45RA/62L、CD4/DR/38、 CD8/DR/38、CD3/4/45RO、CD3/4-/45RO、CD14/16/DR和CD14/16/163 主要目标和假设是 1)确定随机接受延期抗逆转录病毒治疗的儿童，如果他们存活8年或更长时间，而CD4没有下降到15%以下，他们的外周血单核细胞是否表现出早期独特的激活或其他标记。 假设：低激活的T细胞亚群和其他T细胞亚群分布，如低激活的细胞毒性T细胞(CD8+DR+CD38+)和高初始T细胞(CD45+RA+62L+)的低或高值预示着那些将不需要抗逆转录病毒治疗的儿童将他们的CD4+T细胞百分比保持在15%以上。 2)确定神经发育障碍儿童是否在其外周血单核细胞上表现出早期独特的激活或其他标记 假设：高激活的细胞毒性T细胞(CD8+DR+CD38+)、激活的单核细胞(CD14+CD16+DR+)和血管周围巨噬细胞(CD14+CD16+CD163+)预测神经发育障碍的儿童。 这项研究补充了由NIH资助的两项合作研究，包括NIAID资助的CIPRA关于何时开始主要研究的赠款，以及来自NICHD和NIMH的神经发育次级研究的补充赠款。这项研究与公共卫生有关，因为它将提供关于血液中某些细胞是否可以预测儿童将出现艾滋病毒疾病恶化或神经发育的知识。这将是决定何时对儿童进行抗逆转录病毒治疗的重要因素。

DESCRIPTION (provided by applicant): This proposed study will evaluate the activation and other surface markers of T and B lymphocytes, natural killer cells and monocytes in children who are enrolled in the PREDICT Study (CIPRA 1U19AI53741-01A1, An open label, randomized study to compare antiretroviral therapy initiation (ART) when CD4+ is between 15- 24% to ART initiation when CD4+ falls below 15% in children with HIV infection and moderate immune suppression). Measurements of the following markers will be performed by flow cytometry in 300 children at baseline and yearly for 3 years: CDS, CD4, CDS, CD19, CD16/56, CD4/45RA/62L, CD8/45RA/62L, CD4/DR/38, CD8/DR/38, CD3/4/45RO, CD3/4-/45RO, CD14/16/DR and CD14/16/163 The primary objectives and hypotheses are to 1) Determine if children randomized to deferred antiretroviral therapy who survive at 8 years and longer without CD4 falling below 15% display an early unique expression of activation or other markers on their peripheral blood mononuclear cells. Hypothesis: Low or high values of activated and other T cell subset distributions such as low activated cytotoxic T cells (CD8+DR+CD38+) and high naive T cells (CD45+RA+62L+) predicts those children who will not need antiretroviral therapy to keep their CD4+ T cell percentages above 15%. 2) Determine if children with neurodevelopment impairment display an early unique expression of activation or other markers on their peripheral blood mononuclear cells Hypothesis: High activated cytotoxic T cells (CD8+DR+CD38+), activated monocytes (CD14+CD16+DR+) and perivascular macrophages (CD14+CD16+CD163+) predict those children with neurodevelopment impairment. This study complements two collaborative research funded by NIH including the NIAID-funded CIPRA grant for the main when to start study and supplemental grants for the neurodevelopment sub-study from both NICHD and NIMH. This study is relevant to public health because it will provide knowledge on whether certain cells in the blood can predict children who will have worsening of HIV disease or neurodevelopment. This will be important in deciding when to treat children with antiretroviral therapy.