Effect of Lactobacillus on genital HIV-1 RNA and DNA shedding in women

乳酸菌对女性生殖器 HIV-1 RNA 和 DNA 脱落的影响

• 批准号: 7622147
• 负责人: JANE E HITTI
• 金额: $ 36.93万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7622147
• 关键词: Accounting; Archives; Bacteria; Bacterial Vaginosis; Cells; Cervical; Cervix Uteri; Child; DNA; Down-Regulation; Endocervix; Equilibrium; Evaluation; Female; Genetic Transcription; Genital system; HIV; HIV-1; Health; Heterosexuals; Host Defense; Hydrogen Peroxide; Inflammatory; Inflammatory Response Pathway; Irrigation; Kenya; Lactobacillus; Lymphocyte; Maintenance; Measures; Mediating; Mothers; Organism; Pathway interactions; Perinatal; Plasma; Polymerase Chain Reaction; Prevention strategy; Probiotics; Process; Production; Public Health; RNA; RNA replication; Relative (related person); Sampling; Sexual Partners; Time; United States; Vagina; Vaginal Douching; Viral; Viral Load result; Virus; Woman; Work; antiretroviral therapy; cohort; cytokine; macrophage; pandemic disease; protective effect; reproductive; transmission process; vaginal fluid; vaginal lactobacilli

DESCRIPTION (provided by applicant): Genital HIV-1 viral load is a major predictor of sexual and perinatal HIV transmission, and strategies to decrease HIV-1 shedding while promoting vaginal health are urgently needed. We hypothesize that hydrogen peroxide-producing Lactobacillus (L. crispatus and L. jensenii), key components of the normal vaginal flora, decrease genital HIV-1 RNA and DNA shedding among HIV-1-infected women by direct viral inhibition and also by relative suppression of potentially pathogenic vaginal bacteria associated with bacterial vaginosis (BV). We propose to evaluate this hypothesis using archived cervicovaginal lavage (CVL) and cervical cytobrush samples from parallel cohorts of HIV-1-infected women in the United States and Kenya. Specifically, we will: 1. Examine the effect over time of L. crispatus, L. jensenii and L. iners presence and concentrations on HIV-1 RNA load in CVL, as well as the effect of these organisms on pro-inflammatory cytokines and other BV-associated flora. We anticipate that acquisition and/or higher concentrations of L. crispatus and L. jensenii (but not L. iners) will result in a significant decrease in CVL HIV-1 RNA, accounting for other factors such as plasma viral load and antiretroviral therapy, and that this protective effect may be mediated by down-regulation of pro-inflammatory cytokines and/or suppression of BV-associated bacteria. 2. Assess the longitudinal effect of vaginal Lactobacillus species, other BV-associated organisms, and pro-inflammatory cytokines on endocervical HIV-1 DNA quantitation, as well as endocervical HIV-1 RNA. We hypothesize that the protective effect of L crispatus and L jensenii will extend to the endocervix and will include a decrease in proliferation of HIV-1-infected cells as well as viral replication. Taken together, these aims will add to our understanding of the mechanisms by which hydrogen peroxide- producing Lactobacillus modulates HIV-1 in the female genital tract, and may add rationale for further evaluation of probiotics as a potential secondary HIV-1 prevention strategy. PUBLIC HEALTH RELEVANCE: The amount of HIV in the vagina and cervix is a major predictor of HIV transmission between sex partners and from mother to child. This study will examine how Lactobacillus, an essential bacteria for vaginal health, works to decrease the amount of HIV in the female reproductive tract.

描述（申请人提供）：生殖器HIV-1病毒载量是性传播和围产期HIV传播的主要预测因子，迫切需要减少HIV-1脱落同时促进阴道健康的策略。我们假设产生过氧化氢的乳杆菌（L. crispatus和L. jensenii）是正常阴道菌群的关键成分，通过直接的病毒抑制和相对抑制与细菌性阴道病（BV）相关的潜在致病性阴道细菌，可以减少HIV-1感染妇女生殖器HIV-1 RNA和DNA的脱落。我们建议使用美国和肯尼亚hiv -1感染妇女平行队列中存档的宫颈阴道灌洗（CVL）和宫颈细胞刷样本来评估这一假设。具体来说，我们将：1。随着时间的推移，研究crispatus、L. jensenii和L. iners的存在和浓度对CVL中HIV-1 RNA载量的影响，以及这些生物体对促炎细胞因子和其他bv相关菌群的影响。我们预计获得和/或更高浓度的crispatus和L. jensenii（但不是L. iners）将导致CVL HIV-1 RNA的显著降低，考虑到其他因素，如血浆病毒载量和抗逆转录病毒治疗，这种保护作用可能是通过下调促炎细胞因子和/或抑制bv相关细菌来介导的。2. 评估阴道乳杆菌种类、其他bv相关生物和促炎细胞因子对宫颈内HIV-1 DNA定量以及宫颈内HIV-1 RNA的纵向影响。我们假设，crispatus和L jensenii的保护作用将扩展到宫颈内，并将包括减少hiv -1感染细胞的增殖以及病毒复制。综上所述，这些目标将增加我们对产生过氧化氢的乳酸杆菌调节女性生殖道中HIV-1的机制的理解，并可能为进一步评估益生菌作为潜在的继发性HIV-1预防策略提供理论依据。公共卫生相关性：阴道和子宫颈中的艾滋病毒数量是性伴侣之间和母婴之间艾滋病毒传播的主要预测指标。这项研究将研究乳酸菌（一种对阴道健康至关重要的细菌）如何减少女性生殖道中的艾滋病毒数量。