GENITAL TRACT VIROLOGY/IMMUNOLOGY AND HIV INFECTION

描述：此应用程序旨在调查 胎儿/新生儿围产期接触感染艾滋病毒的母亲的情况 生殖道分泌物作为垂直传播的机制，以及 生殖道免疫反应在保护人类健康方面的重要性 婴儿从母婴垂直传播HIV-1。为了实现他们的目标， 申请者提出以下假设：(1)垂直率 病毒的传播与病毒的数量直接相关 生殖道；(2)生殖道中的病毒数量各不相同 直接与外周血液中的病毒量， 生殖道炎和宫颈异位，并与之相反 与母亲的CD4计数；(3)HIV特异性抗体的存在和滴度 宫颈灌洗液中的抗体与感染率成反比 变速箱。此外，申请人建议进行 对其他几个问题的初步研究：(I)风险是否 传播的可能性与产科辅助因素的存在有关 包括胎膜破裂的持续时间； 生殖道中病毒的数量与AZT的使用无关，但 定量地减少生殖道中的病毒负担；。(Iii) 外周血液和生殖器艾滋病毒之间存在异质性 (Iv)婴儿病毒分离物是否会有最密切的联系 (V)生殖道分离株对AZT的耐药性 生殖道比敏感菌株更容易传播； 以及(Vi)怀孕前服用AZT的妇女是否更有可能 生殖道中有耐药菌株的女性比开始接受AZT的女性更多 在怀孕期间。 本申请有几个具体目的，即：(1)评估 下生殖道病毒DNA-PCR检测与临床感染的关系 对宫颈阴道灌洗液(CVL)标本进行培养)和垂直 传播；(2)确定临床关系 潜在可修改的因素或重要的预测因素 垂直传播的可能性，以及病毒在 下生殖道；以及(3)评估局部、下生殖道 生殖道传播时的免疫力。 拟议工作的研究人群将包括被录取的妇女 在有适当CVL标本的智者中。恰如其分 用于聚合酶链式反应和抗体检测的样本是可以运输的 迅速送到WITS指定的现场实验室，并在4分钟内冻结 几个小时。来自Brigham和女性网站的参与者的标本将 也要立即进行艾滋病毒培养。CVL标本取自 WITS参与者在注册时、怀孕34周时和2 产后6个月。此外，还将采集血液样本用于 来自布里格姆和妇女网站参与者的PBMC艾滋病毒培养。 临床病史和体检，包括妇科 念珠菌和阴道病原体的培养检查将是 WITS的部分数据是常规获得的。 预计每年将有100-150名妇女/年的样本进行聚合酶链式反应和 WITS 100例血清抗体检测结果分析 存储库。每年将有大约20名妇女的样本 可用于培养。传播性母婴的DNA-PCR样本 对将通过异源双链迁移率分析和测序进行分析。 申请者估计每年将有2-3个配对样本/ 可用于ZDV抗性的测定。

DESCRIPTION: This application is aimed at investigating the importance of peripartum exposure of the fetus/neonate to HIV-infected maternal genital tract secretions as a mechanism for vertical transmission, and the importance of the genital tract immune response in protecting the infant from vertical transmission of HIV-1. To achieve their goals, the applicants propose the following hypotheses: (1) the rate of vertical transmission varies directly with the amount of virus present in the genital tract; (2) the amount of virus in the genital tract varies directly with the amount of virus in the peripheral blood, the amount of genital tract inflammation and cervical ectopy, and varies inversely with the maternal CD4 count; (3) the presence and titer of HIV-specific antibodies in the cervical lavage fluid varies inversely with the rate of transmission. In addition, the applicants propose to conduct preliminary studies on several additional issues: (i) whether the risk of transmission is related to the presence of obstetrical co-factors including duration of rupture of membranes; (ii) whether the presence of virus in the genital tract is independent of AZT use but quantitatively reduces viral burden in the genital tract; (iii) whether there is heterogeneity between peripheral blood and genital HIV isolates; (iv) whether infant viral isolates will be most closely linked to genital tract isolates; (v) whether AZT resistant isolates in the genital tract are more likely to be transmitted than sensitive isolates; and (vi) whether women taking AZT prior to pregnancy are more likely to have resistant isolates in the genital tract than women who begin AZT during pregnancy. This application several Specific Aims, namely: (1) To assess the relationship between lower genital tract virus (detected by DNA-PCR and culture performed on cervico-vaginal lavage(CVL) specimens) and vertical transmission; (2) to determine the relationships between clinical factors that are potentially modifiable or that are important predictors of vertical transmission, and the presence and amount of virus in the lower genital tract; and (3) to assess the impact of local, lower genital tract immunity on transmission. The study population for the proposed work will consist of women enrolled in WITS who have appropriate CVL specimens obtained. Appropriate specimens for PCR and antibody testing are those that can be transported rapidly to a WITS- designated on-site laboratory and frozen within 4 hours. Specimens from participants at the Brigham and Women's site will also undergo immediate culture for HIV. CVL specimens are obtained from WITS participants at the time of enrollment, 34 weeks gestation, and 2 and 6 months postpartum. In addition, blood samples will be taken for PBMC HIV culture from the Brigham and Women's site participants. Clinical histories and physical exams, including gynecological examinations with culture for Candida and vaginal pathogens, will be part of the WITS data routinely obtained. Specimens from 100-150 women/per year are expected for the PCR and antibody determination along with 100 specimens from the WITS repository. Specimens from approximately 20 women/per year will be available for culture. DNA-PCR samples from transmitting mother-infant pairs will be analyzed by heteroduplex mobility analysis and sequencing. The applicants estimate taht 2-3 paired samples/per year will be available for determination of ZDV resistance.