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: 8173044
• 负责人: Preston A Marx
• 金额: $ 6.18万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173044
• 关键词: Adult; Animals; Code; Colposcopy; Computer Retrieval of Information on Scientific Projects Database; Dose; Drug Formulations; Female; Funding; Goals; Grant; HIV; HIV-1; In Vitro; Infection; Inflammation; Institution; Macaca; Macaca mulatta; Modeling; Monkeys; Pharmaceutical Preparations; Prevention; Research; Research Personnel; Resources; Route; Serum; Silicones; Source; Testing; Toxic effect; United States National Institutes of Health; Vagina; Virus; absorption; drug candidate; efficacy testing; non-nucleoside reverse transcriptase inhibitors; receptor; recombinant virus; retrocyclin; transmission process; vaginal microbicide; vaginal transmission

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The SHIV/female rhesus macaque model is being used to evaluate the toxicity and efficacy of 2 candidate vaginal microbicides, RC-101, an HIV co-receptor blocker, and CSIC, a non-nucleoside reverse transcriptase inhibitor. The SIV-HIV recombinant virus, RT-SHIV, carries the HIV-1 RT coding region. This virus is susceptible in vitro to both candidate drugs. This project will interact closely with the other projects 1-3 and the cores that will carry out the in vitro studies needed to validate RC-101 and CSIC for use in the monkey model. The aims of the study are: 1. To assess vaginal and systemic toxicity of CSIC and RC-101 in adult rhesus macaques. Vaginal colposcopy will assess inflammation associated with drugs in the silicone rings that will be specially made for use in macaques. Sera will be tested for absorption of drug(s) and vaginal washes will be used to assess release of drug into the vaginal vault. 2. To determine the minimal infectious dose for RT-SHIV by the vaginal route. Six macaques will be used to determine the minimal infectious dose of RT-SHIV by the vaginal route. 3. To test the efficacy of RC-101 as a vaginal microbicide against RT-SHIV. Twelve female rhesus macaques will be used to test prevention of transmission by vaginal silicone ring application containing RC-101 4. To test the efficacy of CSIC, a non-nucleoside RT inhibitor against vaginal challenge with RT-SHIV. Twelve female rhesus macaques will be used to test prevention of transmission by CSIC containing silicone rings. 5. To test the efficacy of the combination of CSIC and RC-101. The final plan is to deliver both drugs in the same ring formulation. The goal is to show that these 2 drugs can be used together and will afford better protection against HIV-1 vaginal infection than either could alone. Thus far animals have been requested for aim 1.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 SHIV/雌性恒河猴模型用于评价2种候选阴道杀微生物剂RC-101（HIV共受体阻断剂）和CSIC（非核苷逆转录酶抑制剂）的毒性和疗效。SIV-HIV重组病毒RT-SHIV携带HIV-1 RT编码区。该病毒在体外对两种候选药物均敏感。本项目将与其他项目1-3和核心密切互动，这些项目将进行验证RC-101和CSIC在猴模型中使用所需的体外研究。 这项研究的目的是： 1.评估CSIC和RC-101在成年恒河猴中的阴道和全身毒性。阴道镜检查将评估与硅胶环中药物相关的炎症，硅胶环将专门用于猕猴。 将检测血清的药物吸收，并将使用阴道洗液评估药物释放到阴道穹窿中。 2.确定RT-SHIV经阴道感染的最小感染剂量。将使用6只猕猴确定阴道途径RT-SHIV的最小感染剂量。 3.测试RC-101作为阴道杀微生物剂对RT-SHIV的效力。 12只雌性恒河猴将用于测试通过阴道施用含有RC-101的硅胶环预防传播 4.检测CSIC（一种非核苷类RT抑制剂）对RT-SHIV阴道攻击的疗效。 12只雌性恒河猴将用于测试含有硅胶环的CSIC的传播预防作用。 5.测试CSIC和RC-101组合的功效。最终的计划是在相同的环制剂中递送两种药物。目的是证明这两种药物可以一起使用，并且比单独使用更能预防HIV-1阴道感染。 到目前为止，动物已被要求用于目标1。