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，似乎极大地提高了感染艾滋病毒的成年人的存活率。到目前为止，10项研究中有8项发现，GBV-C病毒血症降低了艾滋病毒相关死亡率或改善了治疗反应；这些结果不太可能是虚假的。尽管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GBV-C的作用机制尚不清楚。我们假设，GBV-C感染还可以减少母婴传播HIV(随HIV病毒载量而变化)，并减缓儿童中HIV的进展；这两种情况以前都没有进行过检查。曼谷的围产期研究为研究这些问题提供了一个独特的机会。我们建议分析来自三项CDC围产期研究(一项自然病史和两项临床研究)的母婴血清中的GBV-C抗体和病毒RNA。这项研究的目的是：1.确定母体GBV-C感染(RNA或抗体)是否减少母婴传播；2.确定GBV-C感染状况与艾滋病毒状况和生物、行为和社会经济变量之间的关系；3.检查GBV-C病毒血症是否与HIV感染婴儿的疾病进展缓慢有关；4.检查感染艾滋病毒的母亲中GBV-C母婴传播率与母亲和分娩特征的关系；以及5.检查母亲和婴儿中GBV-C清除的时间。泰国卫生部和疾病预防控制中心的合作提供了来自妇女和婴儿的广泛数据和样本，包括艾滋病毒血清水平和病毒载量、临床、免疫学和血液学指标，以及人口和行为变量。在亚特兰大疾控中心，血清将使用罗氏检测进行抗体检测，病毒RNA将通过内部定量RT-PCR检测。在感染了GBV-C病毒的妇女和儿童中，稍后将对样本进行分析，以确定清除率。数据将通过分层、Logistic回归、Kaplan-Meier和Cox比例风险回归进行分析。到目前为止，关于GBV-C的许多方面仍不清楚，包括它减少艾滋病毒传播和减缓儿童艾滋病毒进展的能力。拟议的研究将提供重要的知识，并可能进一步增强GBV-C对艾滋病毒感染的有益影响的可信度。一个积极的发现将增加额外的基础研究的动力，以阐明生物机制，并潜在地开发新的预防和治疗方式。

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.