TOPICAL MICROBICIDE DRUG COMBINATIONS FOR THE PREVENTION OF SHIV

用于预防 SHIV 的外用杀菌剂药物组合

• 批准号: 8357460
• 负责人: FRANCIS J NOVEMBRE
• 金额: $ 5.95万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357460
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Animals; Anti-Retroviral Agents; Clinical Trials; Clinical Trials Design; Data; Devices; Drug Combinations; Drug Kinetics; Effectiveness; Female; Funding; Future; Gel; Grant; HIV; HIV Infections; HIV vaccine; Integrase Inhibitors; Intervention; Local Microbicides; Macaca; National Center for Research Resources; Pharmaceutical Preparations; Phase; Prevention; Primates; Principal Investigator; Prophylactic treatment; Protocols documentation; Research; Research Infrastructure; Resources; Reverse Transcription; Source; Tenofovir; Time; Tissues; United States National Institutes of Health; Vagina; Vaginal Gel; Vaginal Ring; Woman; cost; design; drug resistant virus; follow-up; inhibitor/antagonist; pandemic disease; simian human immunodeficiency virus; vaginal transmission

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Women are disproportionately affected by the AIDS pandemic globally. In the absence of an effective HIV vaccine, there is a critical need for developing female-controlled biomedical interventions, such as anti-HIV vaginal gels or rings, which can enable women to protect them from acquiring HIV. The CAPRISA 004 study, a phase IIb clinical trial, demonstrated for the first time that a vaginal gel containing the reverse transcription inhibitor Tenofovir (TFV) was safe and effective for reducing HIV infection in women. These findings support the data generated under this protocol, which showed that gels containing 1% TFV was completely protective against vaginal transmission of simian-HIV in macaques. Follow-up studies evaluating the window of protection in macaques revealed that TFV provided durable protection for up to 3 days and that the protection was associated with high TFV levels in vaginal tissues. Additional studies are now underway to assess the efficacy of TFV gels against vaginal transmission of drug-resistant viruses. Furthermore, this protocol also supported projects evaluating gels formulated with integrase inhibitors and showed them to be highly protective for both pre- and post exposure prophylaxis. In addition to gels, we have conducted pharmacokinetic studies in macaques to evaluate TFV release from intravaginal rings (IVRs). This device is designed to deliver sustained drug levels over weeks from a single application. These animal studies have been instrumental in advancing the field by highlighting the high effectiveness of topical antiretroviral prophylaxis and will continue to aid in future clinical trial designs.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在全球范围内，艾滋病大流行病对妇女的影响尤为严重。在缺乏有效的艾滋病毒疫苗的情况下，迫切需要开发由女性控制的生物医学干预措施，如抗艾滋病毒阴道凝胶或环，使妇女能够保护自己不感染艾滋病毒。CAPRISA 004研究是一项IIb期临床试验，首次证明含有逆转录抑制剂泰诺福韦（TFV）的阴道凝胶对减少女性艾滋病毒感染是安全有效的。 这些发现支持了根据该方案生成的数据，该数据表明含有1% TFV的凝胶对猕猴中猴HIV的阴道传播具有完全保护作用。 评估猕猴保护窗口的后续研究显示，TFV提供长达3天的持久保护，并且保护与阴道组织中的高TFV水平相关。目前正在进行其他研究，以评估TFV凝胶对耐药病毒阴道传播的有效性。此外，该方案还支持评价用整合酶抑制剂配制的凝胶的项目，并显示其对暴露前和暴露后预防具有高度保护性。除凝胶外，我们还在猕猴中进行了药代动力学研究，以评价TFV从阴道环（IVRs）中的释放。该装置旨在通过单次应用在数周内提供持续的药物水平。这些动物研究通过突出局部抗逆转录病毒预防的高效性，在推进该领域方面发挥了重要作用，并将继续有助于未来的临床试验设计。