Phase 1/2 trial of Pharmacological HIV-1 Prevention

HIV-1 药理学预防的 1/2 期试验

• 批准号: 6849301
• 负责人: Kimberly Page
• 金额: $ 73.79万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849301
• 关键词: AIDS education /prevention; AIDS therapy; HIV infections; antiAIDS agent; blood cell count; clinical research; clinical trial phase I; clinical trial phase II; cooperative study; disease /disorder proneness /risk; enzyme linked immunosorbent assay; female; high risk behavior /lifestyle; human immunodeficiency virus 1; human subject; human therapy evaluation; immunopharmacology; interview; longitudinal human study; oral administration; patient oriented research; sexually transmitted diseases; therapy compliance; western blottings

DESCRIPTION (provided by applicant): UNAIDS estimates that 14,000 persons are newly infected with HIV-1 every day throughout the world, of which one half are between the ages of 15 and 24. New transmission occurs despite widespread awareness of the modes of HIV-1 transmission, and the protection afforded by condom use. Young women are especially susceptible, due to limited capacity to negotiate the circumstances of sexual activity, including the numbers of sexual partners, the types of sexual partners, and whether condoms are used. For example, we have found that HIV-1 infection in young Cambodian female sex workers reaches a prevalence of 26% only 2 to 3 years after sexual debut. Novel concepts for HIV-1 prevention are urgently needed. We propose to evaluate the acceptability and safety of HIV-1 chemoprophylaxis in a double blind phase I/II placebo controlled randomized trial of an antiretroviral drug among HIV-1 uninfected women at risk. Cambodian women who sell beer, or "beer girls," are targeted for this study because they are readily identified in public places, they have stable employment allowing retention in the study, and they are at high risk for HIV-1 infection. Cambodia is ideal for this study at this time because of the recent explosive spread of HIV-1. The selected antiretroviral agent is FDA approved for human use, allows once-a-day dosing, is well tolerated for several years, and is active against most drug resistant HIV-1 strains. The study will also obtain preliminary information regarding HIV-1 incidence and drug efficacy that are required for planning a phase III trial. We estimate that 200 women treated for up to 24 months are sufficient to evaluate safety and acceptability, and may demonstrate efficacy if the prophylactic effect of the drug and the control group HIV-1 incidence prove to be comparable to estimates from non-human primate studies and Cambodian serosurveillance. This staged approach to prevention research is optimized to generate efficacy information in short time frames through use of pilot randomized studies in groups who suffer explosive HIV-1 spread before long term cohorts can be established. Pilot studies that confirm high incidence and acceptable interventions will be expanded into closely monitored efficacy trials. These studies ultimately aim to break the epidemic cycle of HIV-1 by protecting young women, which may also spare their future children and sexual partners.

描述（由申请人提供）：联合国艾滋病规划署估计，全世界每天有14，000人新感染HIV-1，其中一半年龄在15至24岁之间。尽管人们普遍认识到HIV-1的传播方式，并通过使用避孕套提供保护，但仍发生了新的传播。青年妇女特别容易受到影响，因为她们在性活动的环境方面，包括在性伴侣的人数、性伴侣的类型以及是否使用避孕套等方面的谈判能力有限。例如，我们发现，柬埔寨年轻女性性工作者在初次性行为后仅2至3年，HIV-1感染率就达到26%。迫切需要新的HIV-1预防概念。我们建议在HIV-1未感染的高危女性中进行一项抗逆转录病毒药物的双盲I/II期安慰剂对照随机试验，以评估HIV-1化学预防的可接受性和安全性。这项研究的对象是卖啤酒的柬埔寨妇女或“啤酒女孩”，因为她们在公共场所很容易被发现，她们有稳定的工作，可以留在研究中，而且她们感染艾滋病毒-1的风险很高。由于最近HIV-1的爆炸性传播，柬埔寨目前是这项研究的理想选择。所选的抗逆转录病毒药物是FDA批准用于人类使用的，允许每天一次给药，耐受性良好，可持续数年，对大多数耐药HIV-1菌株有效。该研究还将获得计划III期试验所需的有关HIV-1发病率和药物疗效的初步信息。我们估计，200名妇女治疗长达24个月，足以评估安全性和可接受性，并可能证明有效性，如果药物的预防作用和对照组HIV-1的发病率证明是从非人灵长类动物研究和柬埔寨血清监测的估计可比。这种预防研究的分阶段方法经过优化，可以在建立长期队列之前，通过在遭受爆炸性HIV-1传播的群体中使用试点随机研究，在短时间内产生疗效信息。确认高发病率和可接受干预措施的试点研究将扩大到密切监测的疗效试验。这些研究的最终目的是通过保护年轻妇女来打破艾滋病毒-1的流行周期，这也可能使她们未来的孩子和性伴侣免受伤害。