Periodontitis as a comorbidity in SIV infection and Antiretroviral Therapy

牙周炎作为 SIV 感染和抗逆转录病毒治疗的合并症

• 批准号: 10548688
• 负责人: Prasun K Datta
• 金额: $ 65.96万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548688
• 关键词: 12 year old; 20 year old; Address; Adult; Affect; Age; Aging; Animals; Anti-Retroviral Agents; Biological; Biological Markers; CD4 Positive T Lymphocytes; Characteristics; Chronic; Clinical; Cross-Sectional Studies; Data; Dental Plaque; Dental caries; Development; Diabetes Mellitus; Disease; Documentation; Ecology; Enrollment; Environment; Experimental Designs; HIV Infections; HIV-1; Health; Human; Immune; Immune response; Immune system; Immunity; Immunologics; Impairment; Individual; Infection; Inflammation; Inflammatory; Innate Immune Response; Knowledge; Ligature; Literature; Longitudinal prospective study; Macaca mulatta; Measures; Microbial Biofilms; Modeling; Mouth Diseases; Mucous Membrane; Oral; Oral Characters; Oral cavity; Outcome; Periodontal Diseases; Periodontitis; Periodontium; Pharmaceutical Preparations; Population; Regenerative capacity; Reporting; Research; Research Activity; SIV; Salivary; Serum; Tissues; Tooth structure; Treatment Efficacy; Variant; Viral; Viremia; age effect; age group; aged; antiretroviral therapy; chronic infection; collaborative approach; commensal bacteria; comorbidity; dysbiosis; host microbiome; immune function; improved; innovation; mature animal; microbial; microbiome; microbiome alteration; microbiome composition; microbiota; multidisciplinary; nonhuman primate; novel; oral infection; oral microbiome; pathogenic bacteria; predicting response; response; young adult

Abstract The two major oral diseases of mankind are chronic infections that result in dental caries and periodontitis. There is evidence of specific dynamics of alterations in commensal and pathogenic bacteria related to periodontitis within the normal population that appears to differ with aging and in diabetes. It is unclear, however, how HIV-1 infection and current management with antiretroviral drugs may affect the microbiome and disease. It is also unclear how differences in this oral microbial ecology and systemic viral environment together with host responses contribute to the destruction of the periodontium. Since characteristics of the immune system repertoire are critical for maintaining general health, congenital or acquired disruptors of development of normal immune functions are reflected in altered microbiota across body niches within the population. While extensive literature has been acquired over the last 3+ decades on the features of the oral microbial biofilms in health and periodontitis, these have primarily been reported from cross-sectional studies in adults with chronic periodontitis. The interaction of a microbial dybiosis and dysregulated response in periodontitis coincident with HIV-1 infection and response to antiretroviral therapy (ART) remains unknown. This proposal engages a multi-disciplinary and multi-institutional collaborative approach for the determination of the interaction of the chronic oral infection and inflammatory disease, periodontitis, with the course and characteristics of SIV infections and response to ART. The study will use a nonhuman primate model of ligature-induced periodontitis, which is a well-established model of oral infection, inflammation, and mucosal disease, in Macaca mulatta. The experimental design will address specific knowledge gaps about the interaction of the chronic infection and dysregulated immune responses of periodontitis with the immunological and biologic changes occurring with SIV infection, including: (i) Periodontitis effects on the viremia and CD4+ levels from SIV infection; (ii) SIV effects on the oral microbiome and salivary and serum responses; and (iii) Interaction of periodontitis on ART efficacy. Our over-arching hypothesis is that “Periodontitis and age will synergize to negatively impact parameters of SIV infection and will deleteriously affect the efficacy of ART in managing the SIV infection.” Our proposed studies will be examined in three Specific Aims: Specific Aim 1: To delineate age effects on the oral microbiome and targeted salivary biomarkers in health, changes that occur with experimental periodontitis, and impact of a subsequent SIV infection. Specific Aim 2: To delineate the effect of experimental periodontitis and age on the efficacy of ART treatment for an SIV infection. Specific Aim 3: To delineate the effect of severe periodontitis on the efficacy of existing ART treatment to control an SIV infection.

摘要 人类的两种主要口腔疾病是导致龋齿和牙周炎的慢性感染。那里 是与牙周炎相关的共生菌和病原菌变化的特定动态证据吗？ 在正常人群中，这似乎随着年龄的增长和糖尿病的发生而有所不同。然而，目前还不清楚HIV-1是如何 感染和目前的抗逆转录病毒药物治疗可能会影响微生物群和疾病。它也是 不清楚这种口腔微生物生态和全身病毒环境与宿主之间的差异 反应导致牙周组织的破坏。由于免疫系统的特点 曲目对维持一般健康至关重要，先天或后天干扰正常发育 免疫功能反映在种群内整个身体利基的改变微生物区系中。虽然范围很广 在过去的30多年里，已经获得了关于口腔微生物生物膜在健康和健康方面的特征的文献 牙周炎，这些主要是从成人慢性牙周炎的横断面研究中报告的。 伴发HIV-1感染的牙周炎中微生物代谢异常和反应失调的相互作用 对抗逆转录病毒疗法(ART)的反应仍不清楚。这项建议涉及多学科和 多机构协作方法确定慢性口腔感染与疾病的相互作用 炎症性疾病，牙周炎，具有SIV感染的病程和特点以及对ART的反应。 这项研究将使用非人类灵长类动物的结扎诱导的牙周炎模型，这是一个公认的模型 口腔感染、炎症和粘膜疾病，在猕猴身上。实验设计将解决 关于慢性感染和免疫反应失调的相互作用的具体知识空白 SIV感染引起的免疫学和生物学改变的牙周炎，包括：(I)牙周炎 SIV感染对病毒血症和CD4+水平的影响；(Ii)SIV对口腔微生物群和唾液的影响 和血清反应；以及(Iii)牙周炎对ART疗效的交互作用。我们最重要的假设是 牙周炎和年龄将协同作用，对SIV感染参数产生负面影响，并将是有害的 影响抗逆转录病毒治疗在管理SIV感染方面的有效性。我们建议的研究将从三个具体方面进行研究 目的：特定目标1：描述年龄对口腔微生物群和唾液生物标记物的影响 健康，实验性牙周炎发生的变化，以及随后SIV感染的影响。特定的 目的2：探讨实验性牙周炎和年龄对ART治疗SIV疗效的影响。 感染。具体目标3：描述严重牙周炎对现有ART疗效的影响 控制SIV感染的治疗。