PLACENTA-ANTIHIV THERAPY

胎盘抗艾滋病毒治疗

• 批准号: 2886736
• 负责人: Richard Kermit Miller
• 金额: $ 41.92万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886736
• 关键词: 2'3' dideoxyinosine; 2'3' dideoxynucleoside; AIDS; AIDS therapy; antiAIDS agent; combination chemotherapy; drug adverse effect; gestational age; human immunodeficiency virus; human tissue; in situ hybridization; perfusion; pharmacokinetics; placenta; placental hormones; placental transfer; polymerase chain reaction; tissue /cell culture; vertical transmission; virus infection mechanism; zidovudine

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.

描述：（改编自申请人摘要）本提案将 集中研究完整的人类胎盘绒毛是如何感染 不同的HIV病毒。 是否存在一种不同的能力， 合胞诱导和非合胞诱导HIV毒株感染 在第一个/第三个三个月期间的胎盘将被确定。 具体 感染胎盘细胞类型-合体滋养层，细胞滋养层， 基质细胞、内皮细胞和Hofbauer细胞-将通过原位 PCR/杂交。 一种模拟细胞条件的模型，如 子宫内，并允许定义的性质和定位的艾滋病毒 感染和病毒感染性的胎盘从第一/第三 将使用三个月。 抗艾滋病病毒治疗无论是单独还是联合 联合用药可以降低子宫内未感染的 胎盘将得到解决，同时检查是否有任何显着 单药/多药治疗产生的细胞/胎盘毒性。 宫内感染胎盘对体外抗HIV治疗的反应 将被确定。 将研究两个胎盘群体。 a）感染 目前正在接受抗艾滋病毒治疗的母亲的胎盘。 在 这些胎盘，其中多种抗艾滋病毒治疗有利于胎儿在 减少胎盘感染和艾滋病毒向胎儿的传播 将建立。 体外数据将与临床数据相关联。 信息. B）来自HIV阳性母亲的感染胎盘， 在怀孕期间从未接受过任何抗艾滋病毒治疗， 同时评价单药/多药治疗，并与 在子宫内处理胎盘。 单药/多药的药物动力学/毒性 抗HIV治疗将在延长（16 - 24小时）的双重人类期内进行检查 胎盘灌注条件下，以多次给药的方式。 是 预计这些研究将确定不同的艾滋病毒株 感染不同胎龄的人胎盘， 细胞被感染，并建立如何单/多抗艾滋病毒治疗 可以被代谢/运输并减少人类的HIV感染 胎盘