Oral microbial signatures in perinatal HIV infection

围产期艾滋病毒感染的口腔微生物特征

• 批准号: 10197099
• 负责人: Louise Kuhn
• 金额: $ 59.66万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-12 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197099
• 关键词: 12 year old; 16S ribosomal RNA sequencing; 2 year old; Adult; Affect; African; Age; Age-Months; Antibiotics; Biological Markers; Birth; Breast Feeding; Cells; Child; Clinical; Clinical Trials; Collection; Communities; DNA; Data; Development; Disease; Disease remission; Early treatment; Enrollment; Environmental Risk Factor; Epidemic; Growth; HIV; HIV Infections; HIV antiretroviral; HIV-1; HIV-exposed uninfected infant; Health; Heterogeneity; Hour; Human; Human Microbiome; Immune system; Immunity; Immunologic Markers; Immunologics; Infant; Infection; Interruption; Intervention; Life; Molecular Epidemiology; Mothers; Oral; Oral Characters; Oral cavity; Outcome; Pathogenesis; Pediatric Hospitals; Perinatal; Persons; Population; Primary Infection; Process; Quality of life; Reporting; Sampling; South Africa; Technology; Testing; Time; Tissues; Viral; Viral reservoir; acute infection; age related; antiretroviral therapy; bacterial community; base; clinical predictors; clinically relevant; cohort; design; epidemiology study; improved; infancy; infant infection; information model; insight; microbial; microbial signature; microbiome; microorganism; neonatal period; novel; oral microbial community; perinatal HIV; preadolescence; prospective; recruit; virology

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.

项目摘要 在周围感染儿童的年龄很小的时候就开始抗逆转录病毒疗法（ART） 显示出可减少“病毒储层”的大小，这被认为是艾滋病毒的主要障碍 治愈或缓解。对我们对早期艺术倡议如何影响的理解至关重要 HIV发病机理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，我们提出了一项分子流行病学研究，以研究口服的程度 微生物特征可以用作生物标志物，以预测临床上与临床相关的病毒学和 早期治疗，受HIV感染的婴儿和儿童的免疫学变化。寻找 口头样品中的生物标志物在临床上是可用的，因为非侵入性采样始终是 首选。我们建议在两个感染HIV的人群中表征口腔微生物群落 婴儿和儿童在约翰内斯堡的Rahima Moosa母亲和儿童医院入学 南非。队列1是现在10至12岁之间的260个围产期感染儿童的队列 自2岁以下时开始艺术以来，他们一直在艺术上受到良好控制的年龄。 与队列1平行是来自同一同一的220名年龄匹配的HIV未感染儿童的队列 社区。队列2是一组插入式感染的儿童 新生儿期。招募该队列始于3年前，并且正在进行中。并联 队列2是一群艾滋病毒暴露，未感染的婴儿。我们建议测试 来自这些队列中选定时间点的口头样本。我们将描述细菌 具体目标1将 检验以下假设，即早期的艺术倡议（3个月以下）将留下独特的 在青春期前儿童中可检测到的口腔中的微生物特征 艺术。具体目标2将检验以下假设，即口腔微生物特征将与 在较老的预生殖前感染的儿童中，病毒储存室的大小很好地控制了 关于艺术以及内脏感染的婴儿和幼儿在此期间发起艺术 新生儿期。特定目标3将描述口腔微生物群落中与年龄相关的动态 在非常早（<48小时的生命）治疗的宫内感染的婴儿和艾滋病毒暴露 未感染的婴儿。我们在南部设计了一项大型而严格的流行病学研究 受艾滋病毒流行影响最大的非洲人口。我们有独特的队列 研究案以确定口服微生物特征是否与已知参数相关联 与艾滋病毒缓解有关。