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: 6590071
• 负责人: Kimberly Page
• 金额: $ 42.43万
• 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 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6590071
• 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(由申请者提供)：联合国艾滋病规划署估计，全世界每天有14,000人新感染艾滋病毒-1，其中一半人年龄在15岁至24岁之间。尽管人们普遍认识到艾滋病毒-1的传播方式以及使用避孕套提供的保护，但仍出现了新的传播。年轻女性尤其容易受到影响，因为她们谈判性活动情况的能力有限，包括性伴侣的数量、性伴侣的类型以及是否使用避孕套。例如，我们发现，在柬埔寨年轻的女性性工作者中，艾滋病毒-1的感染率在首次性行为后2到3年内就达到了26%。迫切需要预防艾滋病毒-1病毒的新概念。我们建议在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中评估HIV-1化学预防在未感染HIV-1的风险女性中的可接受性和安全性。柬埔寨卖啤酒的妇女，或“啤酒女孩”，是这项研究的目标，因为她们很容易在公共场所被认出，她们有稳定的工作，可以留在研究中，而且她们感染HIV-1的风险很高。由于最近艾滋病毒-1的爆炸性传播，柬埔寨是目前进行这项研究的理想国家。选定的抗逆转录病毒药物是FDA批准的人类使用，允许每天给药一次，几年来耐受性良好，对大多数抗药性HIV-1毒株都有活性。这项研究还将获得规划第三阶段试验所需的艾滋病毒-1发病率和药物疗效的初步信息。我们估计，接受长达24个月的治疗的200名妇女足以评估安全性和可接受性，如果该药物的预防效果和对照组的HIV-1发病率被证明与非人类灵长类动物研究和柬埔寨血清监测的估计值相当，则可能显示出有效性。这种预防研究的阶段性方法得到优化，通过在长期队列建立之前遭受艾滋病毒-1爆炸性传播的人群中使用试点随机研究，在短时间内产生疗效信息。证实高发病率和可接受干预措施的试点研究将扩大为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女性来打破艾滋病毒-1的流行循环，这也可能使她们未来的孩子和性伴侣免于死亡。