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.

抽象的 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致病菌变化的特定动态的证据 在正常人群中，这种情况似乎随着衰老和糖尿病而有所不同。然而，目前尚不清楚 HIV-1 是如何 感染和当前抗逆转录病毒药物的治疗可能会影响微生物组和疾病。这也是 尚不清楚这种口腔微生物生态学和全身病毒环境与宿主之间的差异如何 反应会导致牙周组织的破坏。由于免疫系统的特点 曲目对于维持总体健康至关重要，先天性或后天性干扰正常发育 免疫功能反映在人群体内不同部位微生物群的改变上。虽然广泛 在过去的 3 多年里，我们获得了有关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，这些主要是从患有慢性牙周炎的成人的横断面研究中报道的。 与 HIV-1 感染同时发生的牙周炎中微生物失调和失调反应的相互作用 抗逆转录病毒治疗（ART）的反应仍然未知。该提案涉及多学科和 多机构协作方法确定慢性口腔感染和 炎症性疾病、牙周炎、SIV 感染的病程和特征以及 ART 的反应。 该研究将使用结扎引起的牙周炎的非人类灵长类动物模型，这是一个成熟的模型 猕猴的口腔感染、炎症和粘膜疾病。实验设计将解决 关于慢性感染与免疫反应失调之间相互作用的具体知识差距 牙周炎伴随 SIV 感染发生的免疫学和生物学变化，包括： (i) 牙周炎 SIV 感染对病毒血症和 CD4+ 水平的影响； (ii) SIV 对口腔微生物组和唾液的影响 和血清反应； (iii) 牙周炎与 ART 疗效的相互作用。我们的首要假设是 “牙周炎和年龄将协同作用，对 SIV 感染参数产生负面影响，并将产生有害影响 影响 ART 在控制 SIV 感染方面的功效。”我们提出的研究将在三个具体方面进行审查 目标：具体目标 1：描绘年龄对口腔微生物组和目标唾液生物标志物的影响 健康状况、实验性牙周炎发生的变化以及随后的 SIV 感染的影响。具体的 目标 2：描述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。