Impact of GBV-C infection on perinatal HIV transmission

描述（由申请人提供）：感染GBV-C（一种非致病性黄病毒）似乎可显著提高HIV感染成人的存活率。迄今为止，10项研究中有8项发现GBV-C病毒血症降低了HIV相关死亡率或改善了治疗反应;这些结果不太可能是人为的。虽然GBV-C可以抑制HIV复制并改变细胞因子和趋化因子的表达，但其作用机制尚不清楚。我们假设GBV-C感染也减少了母婴HIV传播（随HIV病毒载量而变化），并减缓了儿童的HIV进展;以前都没有检查过。曼谷围产期研究为审查这些问题提供了一个独特的机会。我们建议分析母亲和婴儿的血清GBV-C抗体和病毒RNA从三个CDC围产期研究（自然史和两个临床研究）。本研究的主要目的是：1.确定母亲GBV-C感染（RNA或抗体）是否减少母婴HIV传播; 2.确定GBV-C感染状态和HIV感染状态与生物学、行为学和社会经济学变量之间的关系;研究GBV-C病毒血症是否与HIV感染婴儿的疾病进展缓慢有关; 4.研究HIV感染母亲的GBV-C母婴传播率，作为母亲和分娩特征的函数;和5.检查母亲和婴儿中GBV-C清除的时间。泰国卫生部-疾病预防控制中心合作提供了来自妇女和婴儿的大量数据和标本，包括艾滋病毒血清状态和病毒载量、临床、免疫学和血液学指标以及人口统计学和行为变量。在亚特兰大疾病预防控制中心，将使用罗氏检测试剂盒检测血清中的抗体，并使用内部定量RT-PCR检测病毒RNA。在感染GBV-C的妇女和儿童中，将分析随后的样本以确定清除率。将通过分层、logistic回归、Kaplan-Meier和考克斯比例风险回归分析数据。到目前为止，关于GBV-C仍有许多未知之处，包括其减少艾滋病毒传播和减缓儿童艾滋病毒进展的能力。这项拟议的研究将提供重要的知识，并可能进一步提高GBV-C对HIV感染的有益影响的可信度。积极的发现将推动更多的基础研究，以阐明生物学机制，并可能开发新的预防和治疗方法。

DESCRIPTION (provided by applicant): Infection with GBV-C, a non-pathogenic flavivirus, appears to dramatically improve survival in HIV-infected adults. Eight of 10 studies to date found that GBV-C viremia reduced HIV-related mortality or improved therapeutic response; these results are unlikely artefactual. The mechanism by which GBV-C acts is unknown though GBV-C may inhibit HIV replication and alter cytokine and chemokine expression. We hypothesize that GBV-C infection also reduces mother-infant HIV transmission (which varies with HIV viral load) and slows HIV progression in children; neither have been previously examined. The Bangkok perinatal studies provide a unique opportunity to examine these issues. We propose to analyse sera of mothers and infants for GBV-C antibody and viral RNA from three CDC perinatal studies (a natural history and two clinical studies). The objectives of the proposed study are: 1. To determine if maternal GBV-C infection (RNA or antibody) reduces mother-infant HIV transmission; 2. To determine the association between GBV-C infection status and HIV status and biologic, behavioral and socio-economic variables; 3. To examine if GBV-C viremia is associated with slower progression to disease among HIV-infected infants; 4.To examine the rate of GBV-C mother-to-child transmission among HIV infected mothers as a function of maternal and delivery characteristics; and 5. to examine the timing of GBV-C clearance in mothers and infants. Extensive data and specimens from women and infants are available from the Thailand MOPH-CDC collaboration, including HIV serostatus and viral load, clinical, immunologic and hematologic measures, and demographic and behavioral variables. At CDC Atlanta, sera will be tested for antibody using a Roche assay, and for viral RNA with an in-house quantitative RT-PCR test. In women and children with GBV-C infection, later samples will be analyzed to determine the rate of clearance. Data will be analyzed through stratification, logistic regression, and Kaplan-Meier and Cox proportional hazards regression. As yet, much remains unknown about GBV-C, including its ability to reduce HIV transmission and slow HIV progression in children. The proposed study will provide important knowledge and may lend further credibility to the beneficial impact of GBV-C on HIV infection. A positive finding would add impetus to additional basic research to elucidate the biologic mechanisms and potentially develop new modatities of prophylaxis and treatment.