Drug Interactions in Substance Abusers with HIV Infection

说明（由申请人提供）：全世界艾滋病毒/艾滋病的流行和药物滥用对数千万人产生了不利影响。注射药物使用（IDU），主要是阿片类药物，是美国感染艾滋病毒的第二常见途径，在许多西欧国家也是最常见的途径。在前苏联、其他东欧国家、bb0东南亚、中国和其他西太平洋国家，非法使用药物加剧了世界上最不稳定的新出现的艾滋病毒流行病。艾滋病毒/艾滋病和相关的合并症，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。丙型肝炎病毒在美国吸毒者中非常普遍，特别是在合并感染艾滋病毒的吸毒者中，是导致肝功能衰竭和死亡的主要原因。世界人口的三分之一感染了微细菌结核，注射吸毒者中合并感染艾滋病毒的人数不断增加。在过去几十年里，在治疗药物依赖方面取得了重大进展，在治疗艾滋病毒/艾滋病方面也取得了巨大进展。抗逆转录病毒疗法和治疗药物滥用者中结核病和丙型肝炎病毒等其他合并症的成功需要对药物滥用进行同时治疗。艾滋病毒治疗、药物滥用、结核病和丙型肝炎病毒治疗之间的药物相互作用问题也会削弱或逆转治疗。对所有这些疾病都有好处。我们小组首次研究了药物与抗逆转录病毒和药物滥用疗法的相互作用，并在过去二十年中继续在这一领域开展富有成效的工作。我们现在建议药物相互作用的药代动力学和药效学研究与令人兴奋的新的抗逆转录病毒疗法。这些研究将构成本建议的第一个具体目标。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病毒之间的关键药物相互作用。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，这些研究在该资助的五年期间按照逻辑顺序进行。这项工作将由一个经验丰富的互动性团队进行，该团队是药物滥用、艾滋病毒/艾滋病以及结核病和丙型肝炎病毒治疗方面的专家，这些都是本提案所针对的情况。该团队在针对注射吸毒者和其他弱势群体的I、II、III和IV期临床试验中表现熟练且富有成效。

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.