Nonhuman Primate Studies of Tenofovir and UC781

替诺福韦和 UC781 的非人类灵长类动物研究

• 批准号: 8471642
• 负责人: DOROTHY L PATTON
• 金额: $ 50.55万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8471642
• 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' 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; cervicovaginal; efficacy testing; in vivo; microbicide; non-nucleoside reverse transcriptase inhibitors; nonhuman primate; novel; pandemic disease; pharmacokinetic characteristic; preclinical efficacy; preclinical safety; preclinical study; protective effect; reproductive; routine Bacterial stain; simian human immunodeficiency virus; trafficking

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.

研究开发阴道内使用的局部杀微生物剂以预防性传播疾病 包括艾滋病毒在内的传染性疾病（STI）已经持续了十多年。在过去的一年里， 估计有430万人新感染了艾滋病毒。妇女现在几乎占所有成年人的一半 艾滋病毒/艾滋病感染者。对女性受控制的性传播感染预防产品的需求是众所周知的。临床前 局部杀微生物剂产品的安全性和有效性测试必须在人类使用之前进行， 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来评估阴道使用后局部杀微生物剂产品的安全性， 马尾猕猴我们已经使用这个模型来研究单次和重复应用 杀微生物剂对阴道菌群和上皮的作用。我们进行了临床前安全性研究， 含有UC 781（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 这个猕猴模型此外，我们有能力成像（MRI）产品的分散和运输， 女性生殖道。 在这项拟议的合作协议中，一种新型的局部杀微生物剂递送系统，阴道膜，将 与阴道凝胶制剂进行比较。我们将使用我们的猕猴模型来评估安全性，扩散和 本发明提供了含有UC 781和/或替诺福韦的各种膜制剂的药代动力学特征，并比较 这些发现与凝胶制剂的结果一致。最后，我们将评估每种药物的疗效。 使用猕猴模型进行RT-SHIV感染来开发膜产品。这些研究将部分指导 组合局部杀微生物剂递送系统的优化。