Efficacy and Toxicity of CSIC abd Retrocylin in the SIV Virus Challenge Model

CSIC abd Retrocylin 在 SIV 病毒攻击模型中的功效和毒性

• 批准号: 8380861
• 负责人: Preston A Marx
• 金额: $ 41.33万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8380861
• 关键词: Adult; Animal Husbandry; Animal Model; Animal Welfare; Animals; Clinical Trials; Code; Colposcopy; Dose; Drug Formulations; Drug resistance; Environment; Evaluation; Female; Genetic Recombination; Goals; HIV; HIV Entry Inhibitors; HIV-1; Head; Housing; Human; Hybrids; Implant; In Vitro; Infection; Inflammation; Laboratories; Macaca; Macaca mulatta; Modeling; Monitor; Monkeys; Personal Communication; Pharmaceutical Preparations; Phase; Prevention; Prevention approach; Primates; Principal Investigator; Procedures; Publishing; RNA-Directed DNA Polymerase; Reporting; Research; Resources; Reverse Transcriptase Inhibitors; Route; SIV; Serum; Sexual Transmission; Silicones; Surface; Technical Expertise; Testing; Time; Tissues; Topical application; Toxic effect; United States National Institutes of Health; Vagina; Virus; Virus Diseases; Washington; Work; absorption; base; clinical care; cost effective; data exchange; design; efficacy testing; evaluation/testing; experience; in vivo; inhibitor/antagonist; interest; microbicide; non-nucleoside reverse transcriptase inhibitors; nonhuman primate; novel strategies; programs; repository; research study; retrocyclin; simian human immunodeficiency virus; transmission process; vaginal microbicide; vaginal transmission

Project 4 will use the SHIV/female rhesus macaque model to evaluate the toxicity and efficacy of 2 candidate vaginal microbicides, RC-101 and CSIC. Two different SHIVs will be required because RC-101 is HIV-1 env specific and CSIC is HIV-1 RT specific. SHIV162p4 carries the HIV-1 env and RT-SHIV carries the HIV-1 RT coding region. Project 4 will interact closely with the 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. There are 5 aims: 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. Although SHIV162p4 is well characterized for vaginal infection, there are no reports on RT-SHIV infection by a mucosal route. Six macaques will be used to determine the minimal infectious dose of RTSHIV by the vaginal route. 3. To test the efficacy of RC-101 as a vaginal microbicide against SHIV162p4. 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. All animals will be monitored for infection for 6 months. This is a highly collaborative project that will closely coordinate with all other projects.

项目4将使用SHIV/雌性恒河猴模型来评估2个候选药物的毒性和有效性