Oral microbial signatures in perinatal HIV infection

项目摘要 在围产期感染的儿童中，在很小的时候就开始抗逆转录病毒治疗(ART)是 显示减少了被认为是艾滋病毒主要障碍的“病毒库”的大小 治愈或缓解。对扩大我们对早期艺术启蒙如何影响的理解至关重要 艾滋病毒的发病机制正在扩大可以帮助跟踪这些过程的生物标志物的范围。 在这里，我们建议进行一项分子流行病学研究，以调查口腔感染的程度 微生物特征可用作生物标志物来预测临床相关病毒学和 早期治疗、感染艾滋病毒的婴儿和儿童的免疫学变化。查找一个 口腔样本中的生物标记物将在临床上有用，因为非侵入性采样总是 首选。我们建议对两组HIV感染者的口腔微生物群落进行表征。 在约翰内斯堡Rahima Moosa母婴医院登记的婴儿和儿童， 南非。队列1是260名10-12岁的围产期感染儿童的队列 从2岁以下开始就对艺术有很好的控制的年龄。在……里面 与第一组平行的是220名年龄匹配的未感染艾滋病毒的儿童，他们来自同一 社区。Cohort 2是一组宫内感染的儿童，在 新生儿期。这一群体的招募工作于3年前开始，目前仍在继续。与...并行 Cohort 2是在出生时招募的接触艾滋病毒的未感染婴儿的队列。我们打算测试一下 这些队列中选定时间点的口腔样本。我们将描述细菌的特征 利用靶向16S rRNA测序对这些口腔样本中的群落进行分析。具体目标1将 检验这样一种假设，即较早开始抗逆转录病毒治疗(3个月以下)将留下独特的 控制良好的青春期前儿童口腔中可检测到的微生物特征 艺术。《特定目标2》将检验这样的假设：口腔微生物签名将与 控制良好的大龄青春期前围产期感染儿童的病毒库大小 关于抗逆转录病毒治疗以及宫内感染的婴幼儿在 新生儿期。具体目标3将描述口腔微生物群落中与年龄相关的动态 在极早期(生命48小时)接受宫内感染治疗的婴儿和接触艾滋病毒的婴儿之间 未受感染的婴儿。我们在南部设计了一项大规模而严谨的流行病学研究 受艾滋病毒疫情影响最大的非洲人口。我们有独特的群体，可以 研究以确定口腔微生物特征是否与已知参数有关 与艾滋病毒缓解有关。

Project Summary Initiation of antiretroviral therapy (ART) at a young age in perinatally-infected children has been shown to reduce the size of the “viral reservoir,” which is considered the primary obstacle to HIV cure or remission. Critical to expanding our understanding of how early ART initiation influences HIV pathogenesis is expanding the range of biomarkers that can help track these processes. Here we propose a molecular epidemiology study to investigate the extent to which oral microbial signatures can be used as biomarkers to predict clinically-relevant virologic and immunologic changes among early-treated, HIV-infected infants and children. Finding a biomarker in oral samples would be clinically-useful as non-invasive sampling is always preferred. We propose to characterize oral microbial communities in two cohorts of HIV-infected infants and children enrolled at Rahima Moosa Mother and Child Hospital in Johannesburg, South Africa. Cohort 1 is a cohort of 260 perinatally-infected children now between 10-12 years of age who have been well-controlled on ART since initiating it when under 2 years of age. In parallel with Cohort 1 is a cohort of 220 age-matched HIV-uninfected children from the same community. Cohort 2 is a cohort of intrauterine-infected children initiated on ART within the neonatal period. Recruitment into this cohort started 3 years ago and is on-going. In parallel with Cohort 2 is a cohort of HIV-exposed, uninfected infants recruited at birth. We propose to test oral samples from selected time-points from these cohorts. We will characterize bacterial communities in these oral samples using targeted 16S rRNA sequencing. Specific Aim 1 will test the hypothesis that earlier initiation of ART (under 3 months of age) will leave distinct microbial signatures in the oral cavity detectable in pre-adolescent children well-controlled on ART. Specific Aim 2 will test the hypothesis that oral microbial signatures will be associated with the size of the viral reservoir in older pre-adolescent perinatally-infected children well-controlled on ART as well as in intrauterine-infected infants and young children initiating ART during the neonatal period. Specific Aim 3 will describe age-related dynamics in oral microbial communities between very early (<48 hours of life) treated intrauterine-infected infants and HIV-exposed uninfected infants. We have designed a large and rigorous epidemiologic study in the southern African population most affected by the HIV epidemic. We have unique cohorts that can be studied to determine whether oral microbial signatures are associated with known parameters relevant to HIV remission.