Drug Interactions in Substance Abusers with HIV Infection

艾滋病毒感染者的药物相互作用

• 批准号: 7884371
• 负责人: Gerald H. Friedland
• 金额: $ 36.87万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884371
• 关键词: AIDS/HIV problem; Address; Affect; Anti-Retroviral Agents; Antitubercular Agents; Area; Bacteria; Buprenorphine; CCR5 gene; Cessation of life; Chemicals; China; Clinical Trials; Communicable Diseases; Country; Cytochrome P450; Dependency; Development; Disease; Dose; Drug Interactions; Drug Kinetics; Drug usage; Drug user; Epidemic; European; Grant; HIV; HIV Infections; HIV therapy; Hepatitis C; Hepatitis C virus; Illicit Drugs; Individual; Infection; Injecting drug user; Injection of therapeutic agent; Integrase Inhibitors; Isoenzymes; Life; Liver Failure; Methadone; Methodology; Morbidity - disease rate; Opiates; Outcome; Patients; Performance; Pharmaceutical Preparations; Pharmacodynamics; Phase; Population; Population Study; Procedures; Protease Inhibitor; Rifampin; Rifamycins; Route; Southeastern Asia; Substance abuse problem; Therapeutic; Tuberculosis; USSR; Vulnerable Populations; Work; antiretroviral therapy; drug metabolism; effective therapy; experience; improved; inhibitor/antagonist; mortality; neglect; public health relevance; rifapentine; substance abuse treatment; substance abuser; success; tuberculosis drugs; tuberculosis treatment

DESCRIPTION (provided by applicant): The worldwide epidemics of HIV/AIDS and substance abuse adversely affect tens of millions of people. Injection drug use (IDU), largely of opiates, is the second most frequent route of acquisition of HIV in the US and most frequent in many Western European countries. The world's most volatile emerging HIV epidemics are fueled by illicit drug use in the former Soviet Union, other Eastern European countries,[1] Southeast Asia, China and other Western Pacific countries. HIV/AIDS and related co morbid conditions, including hepatitis C (HCV) and tuberculosis (TB), are the major causes of morbidity and mortality among drug users. HCV, highly prevalent among drug users in the US, particularly in those co-infected with HIV, is a major cause of liver failure and death. One third of the world's population is infected with micro bacterium TB, with increasing numbers in IDUs with HIV co infection. Substantial advances in the treatment of chemical dependency and dramatic advances in HIV/AIDS treatment have been made in past decades. The success of antiretroviral therapy and treatment for other co morbid conditions such as TB and HCV in substance abusers requires concomitant treatment of substance abuse. Problematic drug interactions between therapies for HIV, and substance abuse and TB and HCV therapies as well can blunt or reverse therapeutic .benefits for each and all of these diseases. Our group performed the first studies of drug interactions with antiretroviral and substances abuse therapies and have continued to work productively in this area over the past two decades. We now propose pharmacokinetic and pharmacodynamic study of drug interactions with exciting new antiretroviral therapies. These studies will form the first specific aim of this proposal. As second and third aims, we will broaden our work with substance abuse and new antiretroviral therapies to address critical drug interactions between TB and HCV and .substance abuse therapies. To accomplish these aims, we propose three critical studies of antiretroviral and substance abuse therapy, two important neglected studies of TB and substance abuse therapies, one study of TB, substance abuse and antiretroviral and one study of the most promising HCV therapy, in a logical sequential order over the five year course of this grant. This work will be performed by a highly experienced and interactive team, expert in the treatment of substance abuse, HIV/AIDS and TB and HCV, the conditions targeted by this proposal. This team is skilled and productive in the performance of phase I, II, III and IV clinical trials with injection drug users and other vulnerable populations. Public Health Relevance: Injection drug users have high rates of HIV/AIDS and other infectious diseases which are responsible for illness and death. Treatment of substance abuse is necessary for successful treatment of these infections, but interactions between different drugs interfere with treatment success. This grant will perform studies to identify these interactions and improve the treatment of these conditions in this vulnerable population.

描述（由申请人提供）：艾滋病毒/艾滋病和药物滥用的全球流行给数千万人带来了不利影响。注射吸毒 (IDU)（主要是阿片类药物）是美国第二常见的艾滋病毒感染途径，也是许多西欧国家最常见的艾滋病毒感染途径。前苏联、其他东欧国家、[1] 东南亚、中国和其他西太平洋国家的非法药物使用加剧了世界上最不稳定的艾滋病毒流行。艾滋病毒/艾滋病和相关并发症，包括丙型肝炎 (HCV) 和结核病 (TB)，是吸毒者发病和死亡的主要原因。 HCV 在美国吸毒者中非常流行，特别是在同时感染 HIV 的吸毒者中，它是肝衰竭和死亡的主要原因。世界上三分之一的人口感染了结核菌，同时感染艾滋病毒的注射吸毒者人数也在不断增加。过去几十年来，化学依赖性的治疗取得了实质性进展，艾滋病毒/艾滋病治疗也取得了巨大进展。药物滥用者的抗逆转录病毒治疗和其他合并症（例如结核病和丙型肝炎）的成功治疗需要同时治疗药物滥用。 HIV、药物滥用以及结核病和丙肝病毒治疗之间存在问题的药物相互作用也会削弱或逆转所有这些疾病的治疗效果。我们的小组首次进行了药物与抗逆转录病毒和药物滥用疗法相互作用的研究，并在过去二十年中继续在这一领域开展富有成效的工作。我们现在提出药物与令人兴奋的新抗逆转录病毒疗法相互作用的药代动力学和药效学研究。这些研究将构成该提案的第一个具体目标。作为第二个和第三个目标，我们将扩大我们在药物滥用和新的抗逆转录病毒疗法方面的工作，以解决结核病和丙型肝炎之间的关键药物相互作用以及药物滥用疗法。为了实现这些目标，我们提出了三项关于抗逆转录病毒和药物滥用治疗的关键研究，两项关于结核病和药物滥用治疗的重要被忽视的研究，一项关于结核病、药物滥用和抗逆转录病毒的研究以及一项关于最有希望的丙型肝炎病毒治疗的研究，这些研究按逻辑顺序在本次拨款的五年期间进行。这项工作将由经验丰富的互动团队执行，该团队是药物滥用、艾滋病毒/艾滋病、结核病和丙型肝炎治疗方面的专家，这些疾病都是本提案所针对的疾病。该团队在对注射吸毒者和其他弱势群体进行 I、II、III 和 IV 期临床试验方面技术精湛且富有成效。 公共卫生相关性：注射吸毒者感染艾滋病毒/艾滋病和其他传染病的比例很高，这些疾病是导致疾病和死亡的原因。治疗药物滥用对于成功治疗这些感染是必要的，但不同药物之间的相互作用会干扰治疗的成功。这笔赠款将进行研究，以确定这些相互作用并改善对这一弱势群体的这些疾病的治疗。