Oral microbial signatures in perinatal HIV infection

项目摘要 在围产期感染的儿童中，在年轻时开始抗逆转录病毒治疗（ART）， 被证明可以减少“病毒库”的大小，这被认为是艾滋病毒的主要障碍 治愈或缓解。对于扩大我们对早期ART启动如何影响 HIV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，我们提出了一个分子流行病学研究，以调查在何种程度上，口腔 微生物标记可用作生物标志物来预测临床相关的病毒学， 早期治疗的艾滋病毒感染婴儿和儿童的免疫变化。找到一个 口腔样品中的生物标志物将在临床上有用，因为非侵入性采样总是 preferred.我们建议在两组HIV感染者中描述口腔微生物群落的特征， 在约翰内斯堡的Rahima Moosa妇幼医院登记的婴儿和儿童， 南非队列1是260名10-12岁围产期感染儿童的队列 自2岁以下开始ART治疗以来，ART控制良好的年龄。在 与队列1平行的是一个队列，由220名年龄匹配的未感染艾滋病毒的儿童组成， 社区队列2是一个队列的子宫内感染儿童开始抗逆转录病毒治疗， 新生儿期该队列的招募始于3年前，目前正在进行中。平行于 队列2是在出生时招募的暴露于艾滋病毒的未感染婴儿的队列。我们建议测试 来自这些队列的选定时间点的口服样品。我们将描述细菌 使用靶向16 S rRNA测序在这些口腔样本中的群落。具体目标1将 检验早期开始抗逆转录病毒治疗（3个月以下）将留下明显的 青春期前儿童口腔中可检测到的微生物特征 条具体目标2将检验以下假设：口腔微生物特征将与 年龄较大的青春期前围产期感染儿童的病毒储存库大小得到良好控制 在接受抗逆转录病毒治疗的婴儿和幼儿中， 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（出生后<48小时）接受治疗的宫内感染婴儿和 未感染的婴儿我们设计了一个大规模的严格的流行病学研究， 受艾滋病毒流行影响最严重的非洲人口。我们有独特的群体， 研究以确定口腔微生物特征是否与已知参数相关 与艾滋病缓解有关。

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.