Clinical Trial of CNS Penetrating ART to Prevent NeuroAIDS in China

中枢神经系统穿透性ART预防神经艾滋病在中国的临床试验

基本信息

批准号：
8265001
负责人：
Scott L Letendre
金额：
$ 52.45万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8265001
关键词：
ABCB1 gene AIDS clinical trial group AIDS neuropathy AIDS prevention AIDS/HIV problem Accounting Address Adherence Anti-Retroviral Agents Area Biological Assay Biological Markers Biological Preservation Blood - brain barrier anatomy Bone Diseases Brain Brain Injuries CD14 gene CD4 Positive T Lymphocytes CYP2B6 gene Cardiovascular Diseases Caucasians Caucasoid Race Cells Characteristics China Chinese People Chronic Chronic Disease Clinical Clinical Trials Communities Comorbidity Complex Complication Data Development Disadvantaged Disease Disease Progression Dose Drug Industry Drug usage Effectiveness Encephalopathies Enrollment Environment Europe Frequencies Funding Genes Genetic Genetic Markers Genetic Polymorphism Goals Government Guidelines HIV HLA-DR4 Antigen Hepatic Hepatitis Hepatitis B Virus Hepatitis C Hepatitis C virus Hepatitis Viruses High Prevalence Hospitals Human Genetics Impaired cognition Impairment Individual Infection Inflammation Injection of therapeutic agent Interleukin-6 Kidney Diseases Lamivudine Lead Life Link Liver diseases Low Prevalence Medical Mental disorders Metabolic Diseases Metabolism Monocyte Chemoattractant Protein-1 Moods National Institute of Mental Health Nervous system structure Neuraxis Neurocognitive Neuroglia Nevirapine North America Outcome Study Participant Patients Penetration Perception Performance Permeability Pharmaceutical Preparations Pharmacology Phase Population Population Study Prevalence Prevention Procedures Province Public Health Randomized Randomized Controlled Clinical Trials Recovery Regimen Reporting Research Research Infrastructure Research Project Grants Resources Risk Risk Factors Safety Sample Size Single Nucleotide Polymorphism Tenofovir Therapeutic Time United States Variant Viral Load result Viral hepatitis Virus Diseases Work Zidovudine antiretroviral therapy arm base cohort cost cost effective design drug metabolism efavirenz experience follow-up high risk immune activation injured microbial molecular marker nervous system disorder neuropsychological pathogen prevent primary outcome programs public health relevance public-private partnership randomized trial research study response volunteer

项目摘要

DESCRIPTION (provided by applicant): Advances in treatment have transformed HIV disease to a chronic illness in most individuals in the U.S. The most common central nervous system (CNS) complication of chronic HIV disease is HIV-associated neurocognitive disorder (HAND). In the U.S., HAND prevalence estimates range up to 55% of treated individuals. HAND is also common outside the U.S. For example, our current project in China identified that more than a third of nearly 150 treated HIV (+) individuals in Anhui and Yunnan provinces had HAND. Data such as these support that the benefits of antiretroviral therapy (ART) can be incomplete, with many patients not returning to normal neurocognitive performance or, worse, developing new neurocognitive impairment while taking ART. One explanation for this is the limited penetration of some antiretrovirals into the nervous system. Recent reports have identified that worse antiretroviral penetration characteristics are associated with worse control of HIV replication and worse neurocognitive performance. Most reports, however, have focused on treatment - rather than prevention - of HAND. Like many other medical conditions, prevention of HAND may be a more cost-effective public health goal than treating disease that has already occurred. We propose to build on our prior work in China by performing a phase IV, randomized, controlled clinical trial of the safety and effectiveness of ART that differs in its penetration characteristics in 250 ART-naive individuals who have normal neurocognitive performance. The primary objective will be to determine the effects of better penetrating (BP) ART (zidovudine-lamivudine-nevirapine) compared with worse penetrating (WP) ART (tenofovir-lamivudine-efavirenz) on the prevention of HAND. We hypothesize that volunteers who are randomized to BP-ART will be less likely to neurocognitively decline over 96 weeks of observation than those who are randomized to WP-ART. The secondary objective will be to assess the influence on study outcomes of two conditions: persistent immune activation and viral hepatitis. In an exploratory aim, the project will also assess the influence on study outcomes of a concise panel of drug disposition-associated genetic polymorphisms. Demonstrating that HAND can be prevented by using BP-ART should influence HIV treatment guidelines in the U.S., China, and elsewhere and ultimately lead to preservation of normal neurocognitive functioning in people afflicted with HIV/AIDS. PUBLIC HEALTH RELEVANCE: The project proposes to demonstrate that HAND can be prevented by using better penetrating antiretroviral therapy, which should influence HIV treatment guidelines in the U.S., China, and elsewhere and ultimately lead to preservation of normal neurocognitive functioning in people afflicted with HIV/AIDS.

描述（由申请人提供）：治疗的进展已将HIV疾病转化为美国大多数人的慢性疾病，最常见的中枢神经系统（CNS）慢性HIV疾病并发症是与HIV相关的神经认知疾病（Hand）。在美国，手患病率估计范围高达55％的治疗个体。例如，Hand在美国以外的地方也很常见，我们目前在中国的项目确定，在Anhui和Yunnan Provinces中，近150名接受治疗的艾滋病毒（+）个体中有三分之一以上。这样的数据支持抗逆转录病毒疗法（ART）的益处可能是不完整的，许多患者没有恢复正常的神经认知表现，或者更糟糕的是，在服用ART时会产生新的神经认知障碍。一个解释是一些抗逆转录病毒在神经系统中的有限渗透。最近的报道表明，较差的抗逆转录病毒渗透特征与对HIV复制的控制差和神经认知性能较差有关。但是，大多数报告都专注于手工治疗而不是预防。与许多其他医疗状况一样，与治疗已经发生的疾病相比，预防手可能是一个更具成本效益的公共卫生目标。我们建议通过对艺术的安全性和有效性进行IV期，随机，对照临床试验的临床试验，在250名具有正常神经认知性能的艺术人群的渗透特征方面有所不同。主要目标是确定更好的穿透性（BP）ART（Zidovudine-Lamivudine-nevirapine）的影响，而较差的穿透性（WP）ART（Tenofovir-Lamivudine-efavirenz）对预防手动的影响。我们假设，与随机的WP-ART那些观察的志愿者在96周的观察中的神经认知能力下降的可能性较小。次要目标是评估对两种情况的研究结果的影响：持续的免疫激活和病毒肝炎。在探索目的中，该项目还将评估对与药物处置相关的遗传多态性的简明研究结果的影响。可以通过使用BP-ART来预防该手，应影响美国，中国和其他地方的HIV治疗指南，并最终导致患有艾滋病毒/艾滋病患者的正常神经认知功能。公共卫生相关性：该项目建议通过使用更好的穿透性抗逆转录病毒疗法来证明该手可以预防该手，这应影响美国，中国和其他地方的HIV治疗指南，并最终导致患有艾滋病毒/艾滋病患者的正常神经认知功能。