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: 7958237
• 负责人: FRANCIS J NOVEMBRE
• 金额: $ 5.67万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958237
• 关键词: AIDS prevention; AIDS/HIV problem; Adult; Africa South of the Sahara; Anti-Retroviral Agents; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Detergents; Dose; Drug Combinations; Female; Funding; Gel; Generations; Grant; HIV; Human; Institution; Integrase; Integrase Inhibitors; Life; Local Microbicides; Macaca; Modality; Modeling; Nucleosides; Nucleotides; Pharmaceutical Preparations; Pilot Projects; Prevention; Prevention strategy; Primates; Prophylactic treatment; RNA-Directed DNA Polymerase; Reporting; Research; Research Personnel; Resources; Source; Tenofovir; Time; United States National Institutes of Health; Virus; Woman; design; emtricitabine; inhibitor/antagonist; interest; microbicide; 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. 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. In 2007, UNAIDS reported that women comprise 61% of adults in Sub-Saharan Africa living with HIV/AIDS. This highlights the critical need for an effective, female-controlled HIV prevention strategy such as a vaginally-applied microbicide gel, which can enable women to protect themselves from acquiring HIV. First-generation microbicides that had detergent-like activities proved ineffective and have fueled interest in expanding our research efforts on developing topical microbicide gels formulated with antiretroviral (ARV) drugs. Unlike first-generation, these gels are more promising because they can deliver a high dose of potent drugs that can block HIV replication at the mucosal point of entry. To this end, we have successfully formulated and evaluated several gels containing single or combinations of nucleoside/nucleotide reverse transcriptase (emtricitabine and tenofovir) or integrase (L-870812) inhibitors. We have completed efficacy studies for two gels containing tenofovir (TFV) alone or in combination with emtricitabine (FTC) against vaginal transmission using a repeat-challenge macaque model. Both gels were fully protective indicating that drug combinations may not be needed for effective topical prophylaxis. In addition, we have initiated another study to evaluate the window of protection by the tenofovir gel and examine efficacy when virus exposure occurs 3 days after gel application. We also completed a pilot study to assess the efficacy of a gel with an integrase inhibitor and show that it was highly protective demonstrating for the first time the utility of this class of drugs. Our results highlight the high efficacy of topical antiretroviral prophylaxis as a biomedical prevention strategy, support clinical trials in humans, and inform their design by identifying highly effective modalities.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 2007年，联合国艾滋病规划署报告说，在撒哈拉以南非洲艾滋病毒/艾滋病感染者中，妇女占61%。这突出表明，迫切需要一种有效的、由女性控制的艾滋病毒预防战略，如经阴道使用的杀微生物剂凝胶，使妇女能够保护自己免受艾滋病毒感染。具有类似洗涤剂活性的第一代杀微生物剂被证明无效，并激发了我们扩大研究力度，开发与抗逆转录病毒(ARV)药物配制的局部杀微生物剂凝胶的兴趣。与第一代不同，这些凝胶更有希望，因为它们可以提供大剂量的有效药物，可以在黏膜入口点阻止艾滋病毒复制。为此，我们已经成功地配制并评价了几种含有核苷/核苷酸逆转录酶(恩曲他滨和替诺福韦)或整合酶(L-870812)抑制剂单一或组合的凝胶。 我们已经完成了两种含有替诺福韦(TFV)或与恩曲他滨(FTC)联合使用的凝胶对重复挑战猕猴模型的阴道传播的疗效研究。这两种凝胶都具有完全的保护性，这表明可能不需要联合用药来进行有效的局部预防。此外，我们还启动了另一项研究，以评估替诺福韦凝胶的保护窗口，并在凝胶使用3天后检查病毒暴露的有效性。 我们还完成了一项初步研究，以评估含有整合酶抑制剂的凝胶的有效性，并表明它具有高度的保护性，首次证明了这类药物的实用性。我们的结果强调了局部抗逆转录病毒预防作为一种生物医学预防策略的高效性，支持人类临床试验，并通过确定高效的模式来指导其设计。