Drug Interactions in Substance Abusers with HIV Infection

描述(申请人提供)：艾滋病毒/艾滋病的全球流行和药物滥用对数千万人造成不利影响。注射吸毒(IDU)，主要是鸦片类药物，是美国第二常见的艾滋病毒感染途径，在许多西欧国家也是最常见的。前苏联、其他东欧国家、东南亚、中国和其他西太平洋国家的非法药物使用助长了世界上最不稳定的新出现的艾滋病毒流行。艾滋病毒/艾滋病和相关的共病，包括丙型肝炎(丙型肝炎)和结核病(结核病)，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流行，特别是在那些同时感染艾滋病毒的人中，是导致肝功能衰竭和死亡的主要原因。世界上三分之一的人口感染了微小细菌结核病，感染艾滋病毒的注射吸毒者的人数不断增加。在过去几十年中，在治疗化学依赖方面取得了重大进展，在艾滋病毒/艾滋病治疗方面也取得了重大进展。药物滥用者的抗逆转录病毒治疗和对结核病和丙型肝炎等其他共病疾病的治疗要取得成功，就需要同时治疗药物滥用。艾滋病毒治疗和药物滥用以及结核病和丙型肝炎治疗之间存在问题的药物相互作用可能会削弱或逆转这些疾病的治疗益处。我们小组对药物与抗逆转录病毒和药物滥用疗法的相互作用进行了第一次研究，并在过去20年里继续在这一领域进行富有成效的工作。我们现在建议对药物与激动人心的新抗逆转录病毒疗法的相互作用进行药代动力学和药效学研究。这些研究将构成这项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，两项被忽视的关于结核病和药物滥用治疗的重要研究，一项关于结核病、物质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，在这笔赠款的五年过程中按逻辑顺序排列。这项工作将由一个经验丰富和互动的团队进行，他们是治疗药物滥用、艾滋病毒/艾滋病、结核病和丙型肝炎的专家，这是本提案所针对的情况。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娴熟、富有成效。 公共卫生相关性：注射吸毒者艾滋病毒/艾滋病和其他传染病的发病率很高，这是疾病和死亡的罪魁祸首。药物滥用的治疗对于这些感染的成功治疗是必要的，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，并改善这一弱势群体中这些疾病的治疗。

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.