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