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：
8111860
负责人：
Scott L Letendre
金额：
$ 53.39万
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/8111860
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）：治疗的进步已将美国大多数人的 HIV 疾病转变为慢性疾病。慢性 HIV 疾病最常见的中枢神经系统 (CNS) 并发症是 HIV 相关神经认知障碍 (HAND)。在美国，HAND 患病率估计高达 55% 的接受治疗者。 HAND 在美国以外也很常见。例如，我们目前在中国的项目发现，在安徽和云南省近 150 名接受治疗的 HIV (+) 个体中，有超过三分之一患有 HAND。诸如此类的数据表明，抗逆转录病毒治疗 (ART) 的益处可能并不完整，许多患者无法恢复正常的神经认知功能，或者更糟的是，在接受 ART 的同时出现新的神经认知障碍。对此的一种解释是某些抗逆转录病毒药物对神经系统的渗透有限。最近的报告发现，较差的抗逆转录病毒渗透特性与较差的 HIV 复制控制和较差的神经认知能力有关。然而，大多数报告都侧重于手部疾病的治疗，而不是预防。与许多其他医疗状况一样，预防手足口病可能是比治疗已经发生的疾病更具成本效益的公共卫生目标。我们建议在中国之前的工作基础上，对 250 名神经认知表现正常、未接受过 ART 的个体进行一项关于 ART 安全性和有效性的 IV 期随机对照临床试验，该试验的渗透特征有所不同。主要目标是确定渗透性较好 (BP) ART（齐多夫定-拉米夫定-奈韦拉平）与渗透性较差 (WP) ART（替诺福韦-拉米夫定-依非韦伦）相比对预防 HAND 的效果。我们假设，在 96 周的观察期内，被随机分配到 BP-ART 的志愿者比被随机分配到 WP-ART 的志愿者神经认知能力下降的可能性更小。第二个目标是评估两种情况对研究结果的影响：持续免疫激活和病毒性肝炎。在探索性目标中，该项目还将评估与药物处置相关的遗传多态性的简明小组对研究结果的影响。证明使用 BP-ART 可以预防 HAND 应该会影响美国、中国和其他地方的 HIV 治疗指南，并最终导致 HIV/AIDS 患者保持正常的神经认知功能。公共健康相关性：该项目旨在证明可以通过使用更好的渗透性抗逆转录病毒疗法来预防手足口病，这应该会影响美国、中国和其他地方的艾滋病毒治疗指南，并最终导致艾滋病毒感染者/患者保持正常的神经认知功能。艾滋病。