HIV, HCV and Liver Disease Among Injection Drug Users in Chennai, India

印度钦奈注射吸毒者的艾滋病毒、丙型肝炎和肝病

基本信息

批准号：
8133094
负责人：
Shruti H Mehta
金额：
$ 58.09万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2010-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8133094
关键词：
Acquired Immunodeficiency Syndrome Adherence Adverse event Affect Africa Alcohol consumption Alcohols Algorithms Anti-Retroviral Agents Antitubercular Agents Central Asia Clinical Trials Cohort Studies Collaborations Cross-Sectional Studies Developing Countries Diagnostic Double-Blind Method Drug Addiction Drug usage Eastern Europe Education Epidemic Europe Fatty Liver Fibrosis Future Genes Genetic Predisposition to Disease Genetic screening method Genotype HCV Liver Disease HIV Heavy Drinking Hepatic Hepatitis Hepatitis B Virus Hepatitis C Hepatitis C Prevalence Hepatitis C virus Hepatotoxicity Highly Active Antiretroviral Therapy Histologic Home environment Incidence India Infection Injecting drug user Injection of therapeutic agent Insulin Resistance International Intervention Liver Liver Fibrosis Liver diseases Morbidity - disease rate NIH Program Announcements Nevirapine Nucleotides Pattern Persons Pharmaceutical Preparations Phenotype Placebo Control Population Prevalence Questionnaires Randomized Clinical Trials Recruitment Activity Regimen Research Rifampin Risk Risk Factors Sample Size Scientist Secondary to Single Nucleotide Polymorphism Stavudine Steatohepatitis Testing Text Treatment Protocols Tuberculosis Ultrasonography Universities Vitamin E Work antiretroviral therapy burden of illness cohort cost disorder risk experience follow-up high risk improved liver biopsy member mortality novel novel diagnostics public health relevance response tool treatment response tuberculosis treatment

项目摘要

DESCRIPTION (provided by applicant): Proposed is an application in response to PA-09-020, "International Research Collaboration on Drug Addiction." that brings together Johns Hopkins University and the YR Gaitonde Centre for AIDS Research and Education to characterize interactions between HIV, hepatitis C virus (HCV), tuberculosis (TB), alcohol and liver disease among injection drug users (IDUs) in Chennai, India and to inform future treatment initiatives and interventions to reduce the burden of liver disease in a population with a confluence of hepatotoxic factors. In the developed world, liver disease has emerged as a leading cause of morbidity among HIV-infected IDUs. However, little work has been done in developing countries which represent the fastest growing HIV epidemics among IDUs. HCV treatment is not widely available in the developing world; however this disparity will change raising the urgency of understanding how exposures unique to India affect prevalence and forms of liver disease and whether those at greatest risk can be identified with novel, culturally acceptable tools. Accordingly, our aims are: AIM 1: To ascertain the prevalence of fatty liver disease (e.g., steatosis, steatohepatitis) and investigate the hypothesis d4T use, HCV genotype 3, insulin resistance and alcohol use are independently associated; AIM 1.1: To validate existing diagnostic algorithms for steatosis and fibrosis and to compare the predictive accuracy of existing panels (e.g., APRI, FIB-4) with new panels that use low-cost tests and local risk factors; AIM 2: To determine whether steatosis and liver fibrosis impact the incidence of future hepatic adverse events associated with antiretroviral therapy (ART) and anti-tuberculosis therapy (ATT); AIM 3: To begin to pilot interventions to reduce the burden of liver disease among IDUs in India; AIM 3.1. To quantify the acceptability and potential for HCV treatment response (prevalence of single nucleotide polymorphisms [SNPs] in the IL28b gene) among IDUs in India; and AIM 3.2. To conduct a double-blinded placebo controlled randomized clinical trial to determine the efficacy of Vitamin E for the treatment of steatosis. We will achieve these aims through a mix of cross-sectional studies, longitudinal cohort follow-up and a double-blinded placebo controlled randomized clinical trial building on two existing cohorts. For Aim 1, we will use ultrasonography for steatosis and Fibroscan(R) for fibrosis. For Aim 2, we will follow persons semi-annually to identify new initiates of ART and ATT and conduct intensive follow-up after initiation to determine hepatic tolerability. In Aim 3, we will assess acceptability of HCV treatment via questionnaire and potential treatment response via host genetic testing. The Aim 3 trial will be conducted among 100 IDUs with histologic steatohepatitis at baseline. We have a small window of opportunity to prepare for the impending epidemic of liver disease among IDUs in the developing world. These findings will also inform donors such as PEPFAR and GFATM regarding treatment decisions as the prevalence of HIV-HCV co-infection continues to rise as a result of the increasing contribution of injection drug use to the HIV epidemic in the developing countries including Africa. PUBLIC HEALTH RELEVANCE: Injection drug users (IDUs) are at high risk for HIV and hepatitis infections and the long-term complications of these infections, including liver disease, drug-related hepatotoxicity and mortality. The findings from this study will help to inform interventions to reduce the morbidity and mortality associated with drug use, HIV and hepatitis C. to inform interventions to reduce the morbidity and mortality associated with drug use, HIV and hepatitis C.

描述（由申请人提供）：提议是针对PA-09-020的“国际药物成瘾研究合作”的申请。这汇集了约翰·霍普金斯大学和艾滋病研究中心的艾滋病研究和教育中心，以表征艾滋病毒，丙型肝炎病毒（HCV），结核病（TB），钦奈，印度和印度，印度和印度，印度和印度，印度和印度，印度和印度的注射吸毒者中的酒精和肝病之间的相互作用告知未来的治疗计划和干预措施，以减轻肝毒性因素汇合的人群中肝病的负担。在发达国家，肝病已成为艾滋病毒感染的IDU中发病率的主要原因。但是，在发展中国家，这是IDU中增长最快的艾滋病毒流行病的发展中国家。在发展中国家，HCV治疗并非广泛使用。然而，这种差异将改变提高理解印度独有的暴露方式的紧迫性，并影响肝病的流行和形式，以及那些具有最大风险的人是否可以使用新颖的，具有文化上可接受的工具来确定。因此，我们的目的是：目标1：确定脂肪肝病的患病率（例如脂肪变性，脂肪性肝炎）并研究了假设D4T的使用，HCV基因型3，胰岛素抵抗和酒精使用均独立相关；目标1.1：验证现有的脂肪变性和纤维化诊断算法，并比较现有面板（例如APRI，FIB-4）的预测准确性与使用低成本测试和局部风险因素的新面板；目标2：确定脂肪变性和肝纤维化是否影响与抗逆转录病毒疗法（ART）和抗结核治疗（ATT）相关的未来肝脏不良事件的发生率；目标3：开始进行试点干预以减轻印度IDU的肝病负担；目标3.1。量化印度IDU中HCV治疗反应的可接受性和潜力（IL28B基因中单核苷酸多态性[SNP]的流行率）；和目标3.2。进行双盲安慰剂对照随机临床试验，以确定维生素E治疗脂肪变性的功效。我们将通过横截面研究，纵向队列随访以及两次现有队列的双盲安慰剂控制随机临床试验大楼的组合来实现这些目标。对于AIM 1，我们将使用超声检查进行脂肪变性和纤维纤维（R）进行纤维化。对于AIM 2，我们将在半年度关注人员，以确定艺术和ATT的新启动，并在开始后进行密集的随访，以确定肝耐受性。在AIM 3中，我们将通过问卷调查评估HCV治疗的可接受性，并通过宿主基因测试来评估潜在的治疗反应。 AIM 3试验将在基线时在100个IDU中进行组织学脂肪性肝炎进行。我们有一个很小的机会窗口，为发展中国家IDU中即将来临的肝病流行准备。这些发现还将告知PEPFAR和GFATM等有关治疗决定的捐助者，因为HIV-HCV共同感染的流行率不断增加，这是由于注射毒品使用对艾滋病毒在包括非洲在内的发展中国家的艾滋病毒流行的贡献不断增加。公共卫生相关性：注射药物使用者（IDU）有艾滋病毒和肝炎感染的高风险，以及这些感染的长期并发症，包括肝病，与药物有关的肝毒性和死亡率。这项研究的结果将有助于告知干预措施，以降低与药物使用，HIV和肝炎相关的发病率和死亡率。告知干预措施以降低与吸毒，艾滋病毒和肝炎有关的发病率和死亡率。