An Etonogestrel/Ethinyl Estradiol/QGriffithsin (ETG/EE/QGRFT) IVR to Prevent Pregnancy and HIV

用于预防怀孕和艾滋病毒的依托孕烯/乙炔雌二醇/QGriffithsin (ETG/EE/QGRFT) IVR

• 批准号: 9926449
• 负责人: Nina R. Derby
• 金额: $ 106.89万
• 依托单位: POPULATION COUNCIL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-06 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9926449
• 关键词: Adherence; Adverse event; Anti-Retroviral Agents; Antiretroviral resistance; Antiviral Agents; Biological Assay; Biological Response Modifiers; Caliber; Collaborations; Colposcopy; Computer Assisted; Contraceptive Agents; Contraceptive Usage; Contraceptive methods; Counseling; Couples; Cross-Over Studies; Development Plans; Dose; Drug Delivery Systems; Drug Kinetics; Estrogens; Ethinyl Estradiol; Etonogestrel; Excision; Fibroins; Formulation; Frequencies; Future; HIV; HIV Infections; HIV drug resistance; HIV resistance; Hemorrhage; High Pressure Liquid Chromatography; High Risk Woman; Human; In Vitro; Infectious Pregnancy Complications; Institutes; Instruction; Interview; Lead; Lectin; Levonorgestrel; Macaca mulatta; Measurement; Measures; Menstruation; Methodology; Pharmacodynamics; Pilot Projects; Placebos; Plasma; Population; Pregnancy; Prevention; Process; Progestins; Questionnaires; Reporting; Research Design; Resistance; Resistance development; Risk; Safety; Science; Self Assessment; Serious Adverse Event; Sex Behavior; Silicones; Silk; Technology; Testing; Text Messaging; Tissues; Vagina; Vaginal Ring; Viremia; Virus Shedding; Woman; Women' s Health; Work; anti-viral efficacy; base; demographics; design; diaries; efficacy study; experimental study; improved; in vivo; innovation; non-drug; novel; parity; preference; prevent; product development; reproductive tract; safety assessment; sex; side effect; simian human immunodeficiency virus; social; technology development; tool; transcriptome; transcriptome sequencing; transmission process; unintended pregnancy; vaginal fluid

An Etonogestrel/Ethinyl Estradiol/QGriffithsin (EEQ) IVR to Prevent Pregnancy and HIV Several multipurpose prevention technologies (MPTs) have been advanced to prevent unintended pregnancy and HIV. The current MPT development pipeline is dominated by antiretroviral (ARV) products with progestin- only contraception using levonorgestrel. The Population Council, in collaboration with Oak Crest Institute of Science (OCIS), proposes to develop a 90d pod-type IVR containing the progestin etonogestrel (ETG), the estrogen ethinyl estradiol (EE), and the anti-HIV lectin QGriffithsin (QGRFT), hereafter referred to as the EEQ IVR, to prevent unintended pregnancy and HIV. This product offers a highly effective contraceptive combination (used in NuvaRing®) with the extremely potent and stable non-ARV anti-HIV lectin QGRFT. The EEQ IVR offers significant advantages over ARV/progestin-only contraceptive products. It could reduce both the emergence of drug-resistant HIV and the concern of potential increased risk of HIV transmission as well as common irregular bleeding complaints associated with use of a progestin-only contraceptive. Aim 1: The proposed product development plan for the EEQ IVR includes innovative formulation work involving pod IVR designs and the use of silk fibroin to achieve QGRFT release for 90d. We will develop a scalable process to manufacture an EEQ IVR. Aim 2: Two lead EEQ IVRs will be tested in safety/pharmacokinetics/pharmacodynamics studies in rhesus macaques (RMs). We intend that the EEQ IVR will be safe, deliver target API doses for 90d in vivo and demonstrate in vitro efficacy against HIV/SHIV AD8. Based on these studies, the lead RM IVR will be selected and advanced to in vivo efficacy studies in RMs. We postulate that the EEQ IVR will be efficacious against SHIV AD8 in vivo and will not drive resistance. Aim 3: We will conduct a pilot study among 24 US couples to compare adherence, preference and acceptability of 3 placebo silicone IVRs of different external diameters (46mm, 56mm and 66mm) to inform the design of the EEQ IVR. Using a 3-way crossover study design, we will identify the external IVR diameter associated with greatest adherence and preference to inform the final EEQ IVR design. The EEQ IVR has the potential to significantly improve women’s health and advance the MPT and drug delivery fields. The EEQ IVR would be the first non-ARV MPT for women at high risk for both unintended pregnancy and HIV acquisition.

Etonogestel/Ethinyl雌二醇/Qgriffithsin（EEQ）IVR以防止妊娠和HIV 已经采取了几种多功能预防技术（MPT），以防止意外怀孕 和艾滋病毒。当前的MPT开发管道以抗逆转录病毒（ARV）产物为主 仅使用左甲状腺病。人口委员会与橡树冠学院合作 科学（OCIS），提出了开发90D POD型IVR，该IVR含有孕激素Etonogestel（ETG）， 雌激素乙醇雌二醇（EE）和抗HIV讲座Qgriffithsin（QGRFT），此前称为EEQ IVR，以防止意外怀孕和艾滋病毒。该产品提供高效的避孕药 组合（用于NUVARING®）与极具潜力和稳定的非ARV抗HIV凝集素QGRFT。这 EEQ IVR与仅ARV/仅孕激素避孕产品具有显着优势。它可以减少两者 抗药性艾滋病毒的出现以及潜在的艾滋病毒传播风险增加以及 常见的不规则出血投诉与使用仅孕激素的避孕药相关。目标1： EEQ IVR的拟议产品开发计划包括创新的公式工作涉及POD IVR 设计和使用丝纤维蛋白可实现90D的QGRFT释放。我们将开发一个可扩展的过程 生产EEQ IVR。 AIM 2：将测试两个铅EEQ IVR 安全/药代动力学/药物猕猴（RMS）的药物学研究。我们打算EEQ IVR 将是安全的，为体内90D提供目标API剂量，并证明针对HIV/SHIV AD8的体外效率。 基于这些研究，将选择铅RM IVR并将其提高到RMS中的体内效率研究。我们 假设EEQ IVR将对体内的SHIV AD8有效，并且不会驱动抗性。目标3： 我们将在24对夫妇中进行一项试点研究，以比较3 安慰剂硅胶IVR不同的外部直径（46mm，56mm和66mm），以告知设计的设计 EEQ IVR。使用三向跨界研究设计，我们将确定与 最大的依从性和偏好，以告知最终的EEQ IVR设计。 EEQ IVR有潜力 显着改善妇女的健康，并提高MPT和药物输送领域。 EEQ IVR将是 对于意外怀孕和艾滋病毒的高风险妇女，第一个非ARV MPT。