Dynamics of HIV-infection, Oral Innate Immunity and The Development of Oral Diseases in Children

项目摘要/摘要 口腔疾病是世界上最流行的非传染性疾病之一。唾液 抗菌肽(AMPs)是一种受免疫系统调节的蛋白质，可破坏细胞膜的完整性。 细菌的数量。它们的抗菌活性对细菌以及一些病毒和真菌起作用。同时， 中毒素(IL-37)和人类β防御素(HBD 2和3)与龋齿有关，分泌性 白细胞蛋白酶抑制剂(SLPI)具有抑制白色念珠菌生长的作用。有非常多的 关于艾滋病毒携带者幼儿AMP的数据有限。在肯尼亚，大约5%的人口感染了艾滋病毒 呈阳性，估计有10.5万名0-14岁的儿童和青少年感染。伊利诺伊大学 华盛顿和内罗毕大学已经为国立卫生研究院在肯尼亚研究儿科艾滋病毒提供了20年的资金。这 协作非常适合进行这项符合PAR-21-246评估的探索性研究 HIV感染对HIV/AIDS患者口腔疾病发生和发展的影响程度 并通过扩大现有的实验室基础设施来建立全球口腔健康研究能力 允许在艾滋病毒的背景下对唾液AMP进行局部分析。这项纵向研究将在队列中进行 在当地最大的教学和转诊医院Jaramogi Oginga Odinga接受护理的儿童 肯尼亚西部。在12个月内，我们将招募和跟踪300名儿童(3-4岁)，按出场情况进行分层 艾滋病毒：a)感染艾滋病毒(艾滋病毒+/N=100)，b)暴露于艾滋病毒而未感染(HEU/N=100)，以及c)未暴露于艾滋病毒 未感染组(HUU/N=100；对照组)。我们将评估参与者的艺术忠诚度、长度和 治疗方案；牙菌斑；CD4；HIV-1RNA；以及其他药物。我们的目标是：1)描述影响 基线和超过12个月的HIV感染对唾液抗菌肽分泌的影响 随访期。为了配合目前艾滋病毒的医疗护理计划，我们将收集未受刺激的唾液。 (基线、6个月和12个月评估)，以衡量一套全面的AMP：LL-37、hBDS和SLPI。通过 根据HIV暴露(HIV+、HEU、HUU)分层，我们将能够按组测量AMP水平并评估 与分泌有关的因素。2)确定唾液AMP与口腔疾病之间的关系 在艾滋病毒的背景下。在基线、6个月和12个月的研究中，我们将a)：评估AMP的程度 与口腔疾病(加上念珠菌菌落形成单位、唾液流动)的存在和发展有关 在艾滋病毒暴露和相关治疗的背景下，以及b)确定影响这些指标的因素 联想。3)加强现有的艾滋病毒研究能力。我们将扩大现有的人力和基础设施 包括口腔健康研究的资源。虽然目前对唾液AMP的研究是在肯尼亚以外进行的， 我们将在现有实验室资产的基础上，允许当地人进行这些分析，从而开始一系列研究 这增加了肯尼亚的研究机会。

PROJECT SUMMARY/ABSTRACT Oral diseases are among the most prevalent non-communicable diseases (NCDs) worldwide. Salivary antimicrobial peptides (AMPs) are proteins regulated by our immune system that disrupt the membrane integrity of bacteria. Their antimicrobial activity acts on bacteria as well as some viruses and fungi. While levels of cathelicidins (LL-37) and human beta defensins (hBD 2&3) have been associated with dental caries, secretory leukocyte protease inhibitor (SLPI) has been known for inhibiting the growth of Candida albicans. There is very limited data on AMPs in young children living with HIV. In Kenya, where about 5% of the population is HIV positive, there are an estimated 105,000 infected children and adolescents aged 0-14. The University of Washington and the University of Nairobi have >20 years of NIH funding studying pediatric HIV in Kenya. This collaboration is ideally positioned to conduct this exploratory study which is aligned with PAR-21-246 to assess the extent to which HIV infection influences the occurrence and progression of oral diseases among HIV/AIDS Kenyan children and to create research capacity in global oral health by expanding current lab infrastructure to allow local analysis of salivary AMPs in the context of HIV. This longitudinal study will be conducted in a cohort of children who receive care at the Jaramogi Oginga Odinga, the largest local teaching and referral hospital in western Kenya. Over 12 months, we will recruit and follow a cohort of 300 children (3-4y) stratified by presence of HIV: a) HIV-infected (HIV+/N=100), b) HIV exposed uninfected (HEU/N=100), and c) HIV unexposed uninfected (HUU/N=100; CONTROL GROUP). We will assess participants for ART adherence, length and regimen; dental plaque; CD4; HIV-1 RNA; and additional medications. Our aims are to: 1) Describe the impact of HIV infection on the secretion of salivary antimicrobial peptides at baseline and over a 12-month follow-up period. Coinciding with current HIV schedule for medical care, we will collect unstimulated saliva (baseline, 6, and 12-month assessments) to measure a comprehensive set of AMPs: LL-37, hBDs and SLPI. By stratifying by HIV exposure (HIV+, HEU, HUU), we will be able to measure AMP levels by group and assess factors associated with secretion. 2) Determine the associations between salivary AMPs and oral diseases in the context of HIV. At baseline, 6 and 12 months of the study, we will a): assess the degree to which AMPs are associated with presence and progression of oral diseases (plus candida colony forming units, saliva flow rate and pH), within the context of HIV exposure and related treatment, and b) identify factors impacting these associations. 3) Enhance existing HIV research capacity. We will expand current human and infrastructure resources to include oral health research. While currently the study of salivary AMPs is conducted out of Kenya, we will build upon existing lab assets allowing locals to conduct these analyses, thus starting a line of research that increases Kenyan research opportunities.