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

描述（申请人提供）：本拟定研究将评价入组PREDICT研究的儿童的T和B淋巴细胞、自然杀伤细胞和单核细胞的活化和其他表面标志物（CIPRA 1U 19 AI 53741 - 01 A1，开放标签，一项比较CD 4+介于15- 24%时开始抗逆转录病毒治疗（ART）与CD 4+福尔斯低于15%时开始ART的随机研究感染艾滋病毒和中度免疫抑制的儿童）。 在基线和3年内每年对300名儿童进行以下标志物的流式细胞术测量：CDS、CD 4、CDS、CD 19、CD 16/56、CD 4/45 RA/62 L、CD 8/45 RA/62 L、CD 4/DR/38、 CD8/DR/38、CD3/4-/45 RO、CD3/4-/45 RO、CD14/16/DR和CD14/16/163 主要目标和假设是 1)确定随机接受延迟抗逆转录病毒治疗的儿童，如果生存8年或更长时间，CD 4不低于15%，其外周血单核细胞上是否显示出活化或其他标志物的早期独特表达。 假设：低或高值的活化和其他T细胞亚群分布，如低活化细胞毒性T细胞（CD 8 +DR+ CD 38+）和高幼稚T细胞（CD 45 +RA+62 L+）预测那些不需要抗逆转录病毒治疗的儿童将其CD 4 + T细胞百分比保持在15%以上。 2)确定患有神经发育障碍的儿童是否在其外周血单核细胞上显示活化或其他标志物的早期独特表达 假设：高活化的细胞毒性T细胞（CD 8 +DR+ CD 38+）、活化的单核细胞（CD 14 + CD 16 +DR+）和血管周围巨噬细胞（CD 14 + CD 16 + CD 163+）可预测神经发育障碍。 这项研究补充了NIH资助的两项合作研究，包括NIAID资助的CIPRA补助金，用于开始研究的主要时间，以及NICHD和NIMH神经发育子研究的补充赠款。这项研究与公共卫生有关，因为它将提供血液中某些细胞是否可以预测艾滋病毒疾病或神经发育恶化的儿童的知识。这对决定何时用抗逆转录病毒疗法治疗儿童很重要。

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.