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

描述（由申请人提供）：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，迫切需要在促进阴道健康的同时减少HIV-1脱落的策略。我们假设产生过氧化氢的乳酸杆菌（L。crispatus和L. jensenii），正常阴道植物群的关键成分，通过直接抑制病毒以及通过相对抑制与细菌性阴道病（BV）相关的潜在致病性阴道细菌，减少HIV-1感染妇女的生殖器HIV-1 RNA和DNA脱落。我们建议使用存档的宫颈阴道灌洗（CVL）和宫颈细胞刷样本从平行队列的HIV-1感染的妇女在美国和肯尼亚，以评估这一假设。具体来说，我们将：1。检查L随时间的影响。crispatus，L. jensenii和L.研究了CVL中HIV-1 RNA负载的存在和浓度，以及这些微生物对促炎细胞因子和其他BV相关植物群的影响。我们预计，收购和/或更高浓度的L。crispatus和L. jensenii（而不是L. iners）将导致CVL HIV-1 RNA的显著减少，这是其他因素如血浆病毒载量和抗逆转录病毒治疗的原因，并且这种保护作用可能是通过下调促炎细胞因子和/或抑制BV相关细菌介导的。2.评估阴道乳杆菌属、其他BV相关微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。我们推测卷曲乳杆菌和詹氏乳杆菌的保护作用将延伸到宫颈内膜，并将包括减少HIV-1感染细胞的增殖以及病毒复制。总之，这些目标将增加我们对产生过氧化氢的乳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二级HIV-1预防策略增加理由。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因素。这项研究将研究乳酸杆菌，阴道健康的基本细菌，如何减少女性生殖道中的艾滋病毒数量。

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.