PLACENTA-ANTIHIV THERAPY

描述：(改编自申请者摘要)本提案将 关注完整的人类胎盘绒毛是如何感染的 不同的艾滋病毒毒株。是否有一种区分能力 合胞体诱导和非合胞体诱导的HIV毒株感染人 将确定妊娠前三个月/晚期的胎盘。特定的 感染胎盘细胞类型-合体滋养层细胞，细胞滋养层细胞， 基质细胞、内皮细胞和霍夫鲍尔细胞-将通过原位测定 聚合酶链式反应/杂交。模拟细胞条件的模型，如中所述 并允许定义艾滋病毒的性质和本地化 1/3胎盘感染及病毒感染性 将使用三个月的孕期。抗艾滋病毒治疗是单独进行还是在 联合应用可降低非宫内感染者的传染性 胎盘将被解决，同时检查是否有明显的 单一/多重治疗所产生的细胞/胎盘毒性。 宫内感染胎盘对体外抗HIV治疗的反应 将会被确定。将对两个胎盘种群进行研究。A)感染 目前正在接受抗艾滋病毒治疗的母亲的胎盘。在……里面 这些胎盘，其中多种抗艾滋病毒治疗对胎儿有利 减少胎盘感染和艾滋病毒传播给胎儿 将会建立起来。体外数据将与临床相关。 信息。B)艾滋病毒阳性母亲的感染胎盘，她们有 在怀孕期间从未接受过任何抗艾滋病毒治疗，将 同时对单一/多种疗法进行评估并与 胎盘在宫内治疗。单药/多药的药代动力学/毒性 抗艾滋病毒治疗将在延长(16-24小时)的双重人类期限下进行检查 多剂量给药的胎盘灌流条件。它是 预计这些研究将确定不同的艾滋病毒毒株 感染不同胎龄的人胎盘，哪些胎盘 细胞正在被感染，并建立单一/多重抗艾滋病毒治疗 可以被代谢/运输，并减少人类感染艾滋病毒 胎盘。

DESCRIPTION: (Adapted from Applicant's Abstract) This proposal will concentrate on how the intact human placental villous becomes infected with different strains of HIV. Whether there is a differential ability of syncytial-inducing and non-syncytial-inducing HIV strains to infect the placenta during the first/third trimesters will be determined. Specific infection of placental cell types - syncytiotrophoblast, cytotrophoblast, stromal, endothelial, and Hofbauer cells - will be determined by in situ PCR/hybridization. A model that simulates cellular conditions as noted in utero and allows definition of the nature and localization of the HIV infection and viral infectivity for placentae from the first/third trimesters will be used. How anti-HIV therapy either alone or in combination can reduce the infectivity of the non-in utero infected placentae will be resolved, while examining if there is any significant cellular/placental toxicity being produced by the mono/multiple therapy. How the in utero infected placentae responds to anti-HIV therapy in vitro will be determined. Two placental populations will be studied. a) Infected placentae from mothers who are currently receiving anti-HIV therapy. In these placentae, which multiple anti-HIV therapy benefit the fetus in reducing the infection of the placenta and transmission of HIV to the fetus will be established. The in vitro data will be correlated with the clinical information. b) The infected placentae from HIV-positive mothers, who have never been treated during pregnancy with any anti-HIV therapy, will be evaluated for mono/multiple therapy concurrently and compared with those placentae treated in utero. The pharmaco-kinetics/toxicity of mono/multiple anti-HIV therapy will be examined under extended (16-24 hr) dual human term placental perfusion conditions in a multiple-dosing manner. It is anticipated that these studies will establish how different HIV strains infect the human placenta from different gestational ages, which placental cells are being infected, and establish how mono/multiple anti-HIV therapy can be metabolized/ transported and reduce the HIV infection in the human placenta.