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

HIV 儿童免疫学长期无进展的预测因素

• 批准号: 7900925
• 负责人: Jintanat Ananworanich
• 金额: $ 7.79万
• 依托单位: HIV-NAT, THE THAI RED CROSS AIDS RCH CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-15 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7900925
• 关键词: 12 year old; Adult; Age; Applications Grants; B-Lymphocytes; Blood; CD19 gene; CD4 Positive T Lymphocytes; Cells; Child; Complement; Cytotoxic T-Lymphocytes; Data; Disease; Disease Progression; Enrollment; Flow Cytometry; Funding; Grant; HIV; HIV Infections; Immunologics; Immunosuppression; Impairment; Knowledge; Measurement; Mental Health; National Institute of Child Health and Human Development; National Institute of Mental Health; Natural Killer Cells; Neurologic; Peripheral Blood Mononuclear Cell; Population; Public Health; Publishing; Randomized; Research; Research Personnel; Research Project Grants; Staging; Surface; Symptoms; T-Lymphocyte; T-Lymphocyte Subsets; United States National Institutes of Health; antiretroviral therapy; arm; falls; macrophage; monocyte; neurodevelopment; open label; programs; response

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.

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+艾滋病毒感染和中度免疫抑制儿童的15％低于15％）。 以下标记的测量值将通过300名儿童的流式细胞术在基线和每年的3年中进行：CDS，CD4，CDS，CD19，CD19，CD19，CD16/56，CD4/45RA/62L，CD8/45RA/62L，CD4/DR/DR/38，CD8/45RA/62L， 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）确定在8年及以下的儿童中随机延迟了抗逆转录病毒疗法，而没有CD4降至15％以下的儿童在其周围血液单核细胞上表现出早期的激活或其他标志物的早期独特表达。 假设：活化和其他T细胞子集分布的低值或高值，例如低活化的细胞毒性T细胞（CD8+DR+CD38+）和高天真T细胞（CD45+RA+62L+）预测那些不需要抗逆转录病毒治疗的儿童以保持其CD4+T细胞以上15％。 2）确定神经发育障碍儿童是否在其周围血液单核细胞上表现出早期的激活或其他标记的独特表达 假设：高活化的细胞毒性T细胞（CD8+DR+DR+CD38+），活化的单核细胞（CD14+CD16+DR+）和血管周围巨噬细胞（CD14+CD16+CD163+）预测那些患有神经内皮障碍的儿童。 这项研究补充了由NIH资助的两项合作研究，其中包括NIAID资助的CIPRA赠款，用于开始学习的主要何时开始学习，并为NICHD和NIMH的神经发育子研究补充赠款。这项研究与公共卫生有关，因为它将提供有关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。这对于决定何时治疗抗逆转录病毒疗法的儿童很重要。