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

描述（由申请人提供）：建议是一个应用程序，以回应PA-09-020，“国际研究合作对药物成瘾。“汇集了约翰霍普金斯大学和YR Gaitonde艾滋病研究和教育中心，以描述印度钦奈注射吸毒者（IDUs）中艾滋病毒，丙型肝炎病毒（HCV），结核病（TB），酒精和肝病之间的相互作用，并为未来的治疗计划和干预措施提供信息，以减少肝毒性因素汇合的人群中肝病的负担。在发达国家，肝病已成为感染艾滋病毒的注射吸毒者发病的主要原因。然而，在注射吸毒者中艾滋病毒流行病增长最快的发展中国家，所做的工作很少。HCV治疗在发展中国家并不普遍;然而，这种差异将改变，提高了解印度独特的暴露如何影响肝病的患病率和形式以及是否可以用新的，文化上可接受的工具来识别最大风险的紧迫性。因此，我们的目的是：目的1：确定脂肪肝疾病的患病率（例如，脂肪变性，脂肪性肝炎），并研究假设d4 T的使用，HCV基因型3，胰岛素抵抗和酒精使用是独立相关的; AIM 1.1：验证现有的脂肪变性和纤维化的诊断算法，并比较现有面板的预测准确性（例如，APRI，FIB-4）与使用低成本检测和当地风险因素的新面板; AIM 2：确定脂肪变性和肝纤维化是否影响与抗逆转录病毒治疗（ART）和抗结核治疗（ATT）相关的未来肝脏不良事件的发生率; AIM 3：开始试点干预措施，以减少印度注射吸毒者的肝脏疾病负担; AIM 3.1。量化印度注射吸毒者中HCV治疗应答的可接受性和潜力（IL 28 b基因单核苷酸多态性[SNP]的患病率）;和AIM 3.2。进行一项双盲安慰剂对照随机临床试验，以确定维生素E治疗脂肪变性的疗效。我们将通过横断面研究、纵向队列随访和基于两个现有队列的双盲安慰剂对照随机临床试验来实现这些目标。对于目标1，我们将使用超声波检查脂肪变性，使用Fibroscan（R）检查纤维化。对于目标2，我们将每半年对患者进行一次随访，以确定ART和ATT的新启动者，并在启动后进行强化随访，以确定肝脏耐受性。在目标3中，我们将通过问卷调查评估HCV治疗的可接受性，并通过宿主基因检测评估潜在的治疗反应。Aim 3试验将在100名基线时患有组织学脂肪性肝炎的注射吸毒者中进行。我们有一个小小的机会之窗来为发展中国家注射吸毒者中即将到来的肝病流行做好准备。这些调查结果还将为总统艾滋病紧急救援计划和全球抗击艾滋病、结核病和疟疾基金等捐助者提供有关治疗决定的信息，因为在包括非洲在内的发展中国家，注射吸毒对艾滋病毒流行的影响越来越大，导致艾滋病毒和丙型肝炎病毒合并感染的流行率继续上升。 公共卫生相关性：注射吸毒者感染艾滋病毒和肝炎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的风险很高。这项研究的结果将有助于采取干预措施，减少与吸毒、艾滋病毒和丙型肝炎相关的发病率和死亡率。 为减少与吸毒、艾滋病毒和丙型肝炎有关的发病率和死亡率的干预措施提供信息。

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.