Nonhuman Primate Studies of Tenofovir and UC781

替诺福韦和 UC781 的非人类灵长类动物研究

基本信息

批准号：
7898232
负责人：
DOROTHY L PATTON
金额：
$ 37.82万
依托单位：
MAGEE-WOMEN'S RES INST AND FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-15 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7898232
关键词：
AIDS/HIV problem Adult Animals Anti-Bacterial Agents Anti-Retroviral Agents Antibodies Antiviral Agents Biopsy Biopsy Specimen CD4 Lymphocyte Count Cell secretion Cervical Characteristics Clinical Research Clinical Trials Collaborations Contrast Media Cytology DNA Data Dosage Forms Drug Formulations Drug Kinetics Ecosystem Epithelium Exposure to Female Film Gel Genital system Goals Gram&apos s stain HIV High Pressure Liquid Chromatography Hour Human Image Infection Infection prevention Irrigation Kinetics Life Local Microbicides Macaca Macaca nemestrina Magnetic Resonance Imaging Measurement Measures Microbiology Modeling Monitor MultiHance Nucleotides Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Plasma Prevention Preventive RNA Research Reverse Transcriptase Inhibitors Safety Sampling Serum Sexually Transmitted Diseases Site Swab System Tenofovir Testing Tissues U-Series Cooperative Agreements UC 781 Vagina Vaginal Douching Vaginal Gel Viral Load result Virus Woman efficacy testing in vivo microbicide non-nucleoside reverse transcriptase inhibitors nonhuman primate novel pandemic disease pharmacokinetic characteristic preclinical safety preclinical study protective effect reproductive routine Bacterial stain simian human immunodeficiency virus trafficking

项目摘要

Research efforts to develop topical microbicides for intravaginal use for the prevention of sexually transmitted infections (STI) including HIV have been ongoing for over a decade. In the past year an estimated 4.3 million people became newly infected with HIV. Women now represent almost half of all adults living with HIV/AIDS. The need for a female controlled STI preventive product is well understood. Preclinical safety and efficacy testing of topical microbicide products must be performed prior to human use to assess the product's effects on the vaginal ecosystem and to assess potential anti-HIV activity. We have developed a useful model to evaluate the safety of topical microbicide products after vaginal use in the pigtailed macaque. We have used this model to study the effects of single and repeated applications of microbicides on vaginal microflora and epithelium. We have conducted preclinical safety and pharmacokinetic studies of vaginal gel formulations containing UC781 ( 1% and 0.1%) and tenofovir (1%) in this macaque model. In addition, we have the ability to image (MRI) product dispersal and transport in the female reproductive tract. In this proposed cooperative agreement, a novel delivery system for topical microbicides, vaginal films, will be compared to vaginal gel formulations. We will use our macaque model to assess safety, dispersal and pharmacokinetic characteristics of various film formulations containing UC781 and/or tenofovir, and compare these findings to those compiled for gel formulations. Finally, we will assess the efficacy of each of the developed film products using a macaque model for RT-SHIV infection. These studies will in part guide the optimization of a combination topical microbicide delivery system.

开发局部杀菌剂以用于预防性行为的局部杀菌剂的研究工作包括艾滋病毒在内的传播感染（STI）已经持续了十多年。在过去的一年中估计有430万人被艾滋病毒新近感染。现在，女性几乎代表了所有成年人的一半与艾滋病毒/艾滋病生活在一起。人们对女性受控预防产品的需求已得到充分了解。临床前局部菌心生产产品的安全性和有效性测试必须在人使用前进行评估该产品对阴道生态系统的影响并评估潜在的抗HIV活性。我们已经开发了一个有用的模型，以评估阴道使用后局部杀菌剂产品的安全性辫子的猕猴。我们已经使用此模型来研究单一和重复应用的影响阴道菌群和上皮上的菌物。我们进行了临床前的安全性和含有UC781（1％和0.1％）和替诺福韦（1％）的阴道凝胶制剂的药代动力学研究这个猕猴的模型。此外，我们还具有图像（MRI）产品分散和运输的能力女性生殖道。在这项提出的合作协议中与阴道凝胶制剂进行比较。我们将使用猕猴模型评估安全性，分散和包含UC781和/或Tenofovir的各种膜配方的药代动力学特征，并比较这些发现是针对凝胶配方汇编的那些发现的。最后，我们将评估每个的功效使用用于RT-SHIV感染的猕猴模型开发了膜产品。这些研究将部分指导组合局部菌心递送系统的优化。