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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 SHIV/雌性恒河猴模型被用来评估两种候选阴道杀菌剂的毒性和功效：RC-101（一种 HIV 共受体阻断剂）和 CSIC（一种非核苷逆转录酶抑制剂）。 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。该项目将与其他项目 1-3 以及将进行验证 RC-101 和 CSIC 在猴子模型中使用所需的体外研究的核心密切互动。 该研究的目的是： 1. 评估CSIC和RC-101对成年恒河猴的阴道和全身毒性。阴道阴道镜检查将评估与专门用于猕猴的硅胶环中的药物相关的炎症。 将测试血清的药物吸收情况，并使用阴道冲洗液来评估药物释放到阴道穹窿中的情况。 2. 确定RT-SHIV经阴道途径的最低感染剂量。将使用六只猕猴来确定通过阴道途径的 RT-SHIV 的最低感染剂量。 3. 测试RC-101作为阴道杀微生物剂对抗RT-SHIV的功效。 将使用 12 只雌性恒河猴来测试通过含有 RC-101 的阴道硅胶环应用来预防传播 4. 测试CSIC（一种非核苷RT抑制剂）对抗RT-SHIV阴道攻击的功效。 将使用 12 只雌性恒河猴来测试含有硅胶环的 CSIC 的传播预防效果。 5.测试CSIC与RC-101组合的功效。最终计划是在同一个环制剂中提供两种药物。目的是证明这两种药物可以一起使用，并且比单独使用任何一种药物都能更好地预防 HIV-1 阴道感染。 到目前为止，目标 1 已要求动物。