EFFICACY AND TOXICITY OF CSIC AND RETROCYCLIN IN THE SIV VAGINAL CHALLENGE MODEL

CSIC 和逆环素在 SIV 阴道挑战模型中的功效和毒性

• 批准号: 8358131
• 负责人: Preston A Marx
• 金额: $ 5.78万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8358131
• 关键词: Animals; Biopsy; Blood; Blood specimen; Colposcopy; Depo Provera; Dose; Endoscopic Biopsy; Funding; Grant; HIV; HIV Entry Inhibitors; Hour; Implant; Intestines; Macaca mulatta; Modeling; Monitor; National Center for Research Resources; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Route; SIV; Source; Tissue Sample; Toxic effect; Toxicity Tests; United States National Institutes of Health; Vagina; Vaginal Ring; Virus; Virus Diseases; absorption; cost; microbicide; non-nucleoside reverse transcriptase inhibitors; retrocyclin; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall objective of this study is to evaluate the toxicity and efficacy of two microbicides  an HIV entry inhibitor (RC-101) and an HIV non-nucleoside reverse transcriptase inhibitor (CSIC) against RT-SHIV virus challenge. There are five specific aims to achieve this objective. Aim 1 will assess the vaginal and systemic toxicity of RC-101 and CSIC. Microbicide rings will be placed in the vaginal vault of Rhesus macaques (Macaca mulatta). Blood, tissue sampling and colposcopies will be performed to determine vaginal and systemic absorption and toxicity as well as to determine the release rate of the microbicides. Aim 2 will determine the minimal infectious dose of RT-SHIV by the vaginal route. Six Rhesus macaques will be inoculated with RT-SHIV via the vaginal route and blood samples will be collected to monitor viral infection. To date, two animals have been treated with Depo-Provera and inoculated with 10 TICD50 RT-SHIV. The remaining four animals will be inoculated with the dose dependent upon the results of the first two animals. Aims 3, 4 and 5 will determine the efficacy of each microbicide individually, as well as in combination, against RT-SHIV challenge. Vaginal rings containing either RC-101, CSIC, a combination of the two or the vehicle only (6 animals in each group) will be implanted vaginally. The animals will be challenged vaginally 24 hours later with RT-SHIV. Blood samples, vaginal biopsies and endoscopic intestinal pinch biopsies will be collected to monitor for viral infection. Thus far, six animals have been assigned to test the toxicity and efficacy of CSIC (Aims 1 and 3).

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 这项研究的总体目的是评估两种微生物抑制剂（RC-101）和HIV非核苷逆转录酶抑制剂（CSIC）对RT-SHIV病毒挑战的毒性和疗效。 实现这一目标有五个特定的目标。 AIM 1将评估RC-101和CSIC的阴道和全身毒性。 微生物环将放置在鼠尾草猕猴（Macaca Mulatta）的阴道库中。 将进行血液，组织采样和阴道镜，以确定阴道和全身吸收和毒性，并确定微生物的释放速率。 AIM 2将通过阴道途径确定RT-SHIV的最小感染剂量。 RT-SHIV将通过阴道途径接种六个恒河猴，并将收集血液样本以监测病毒感染。 迄今为止，已经用depo-provera处理了两只动物，并用10个TICD50 RT-SHIV接种。剩下的四只动物将接种剂量，取决于前两只动物的结果。 AIM 3、4和5将对RT-SHIV挑战分别和组合确定每个杀菌剂的功效。 包含RC-101，CSIC，两者或仅车辆的组合（每组中有6只动物）的阴道环将被阴道植入。 24小时后，将通过RT-SHIV阴道挑战这些动物。 将收集血液样本，阴道活检和内窥镜肠击活检以监测病毒感染。 到目前为止，已经分配了六只动物来测试CSIC的毒性和功效（目标1和3）。