Evaluations of medication assisted treatments for substance use disorders among persons living with and at risk for HIV infection

项目摘要： 现申请续期为期五年的独立科学家奖(K02)，以协助继续 受保护的时间允许桑德拉·斯普林格博士继续她富有成效的研究生涯，包括干预 这将改善艾滋病毒携带者中艾滋病毒与物质使用障碍(SUD)治疗的整合 (PLH)和那些有感染艾滋病毒风险的人。这一奖项也将增加她致力于指导的时间。 分享这一兴趣的年轻调查人员。艾滋病毒感染率至少高出28到50倍。 在注射毒品者(PWID)中与普通人群进行比较。在北美，有一种 2012年，在200万残疾人中，估计有267,000人感染艾滋病毒(PLHS)。阿片类药物代表 注射药物的主要类别，2013年，517,000名成年人报告在过去一年中使用海洛因， 与2007年相比，增长了约150%。药物辅助治疗(MAT) 阿片成瘾，再加上针头和注射器交换计划(NESP)，大大减少了 在残疾人中传播艾滋病毒的风险。此外，MAT降低了HIV阳性PWID患者的死亡率(这是 否则比艾滋病毒阴性的PWID患者高出3倍)。MAT主要以以下形式提供 用美沙酮或丁丙诺啡治疗阿片激动剂，并新出现阿片拮抗剂治疗 (如缓释纳曲酮)。然而，目前还没有可用的建议来指导 制膜剂的选择。此外，尽管有大量证据表明阿片类药物对人体的免疫调节作用 免疫反应方面，还没有研究使用系统生物学方法来评估MAT制剂的 对慢性炎症等参数的影响-对艾滋病毒疾病的进展和 即使是精英控制员或在没有抗逆转录病毒治疗的情况下实现了病毒学控制的个人也存在 (艺术)。为了解决这些问题，斯普林格博士获得了NIDA资助的5年R01评估 与她在耶鲁医学院的合作伙伴Shaw博士一起进行了一项 HIV阳性(关于抗逆转录病毒治疗)与HIV阴性PWID的前瞻性纵向研究，从MAT开始，从 康涅狄格州纽黑文最大的戒毒中心。这项提议的力量在于，斯普林格博士 是：(1)在艾滋病毒和成瘾医学方面有经验；(2)在药理学的新用途方面有经验 干预(MAT)治疗肥皂症以防止复发，使用阿片类药物和酒精作为改善艾滋病毒病毒的手段 抑制；(3)有超过15年的经验，在美国国立卫生研究院资助的PLH中进行SUD和 使用MAT干预；以及(4)是与此正在扩展的应用程序相关联的成功R01上的联合PI 她使用系统生物学评估MAT治疗HIV感染慢性炎症的经验。因此， 个人、我们的医疗保健系统和社会很有可能受益--特别是在减少 艾滋病病毒在社区中的传播。

Project Abstract: This is an application for a renewal of a fiver-year Independent Scientist Award (K02) to assist in the continued protected time to allow Dr. Sandra Springer to continue her productive research career involving interventions that will improve integration of HIV and substance use disorder (SUD) treatment among persons living with HIV (PLH) and those at risk for HIV infection. This award will also increase her time to devote towards mentoring young investigators who share this interest. The prevalence of HIV infection is 28 to at least 50 times higher among people who inject drugs (PWID) compared to the general population. In North America, there were an estimated 267,000 persons living with HIV infection (PLHs) among 2 million PWIDs in 2012. Opioids represent the dominant class of injected agent, and in 2013 517,000 adults reported heroin use within the past year, representing an approximately 150% increase compared to 2007. Medication-assisted treatment (MAT) for opiate addiction, combined with needle and syringe exchange programs (NESP) have substantially reduced the risk of HIV transmission in PWIDs. Moreover, MAT reduces mortality among HIV-positive PWIDs (which is otherwise 3-fold higher than in PWIDs who are HIV-negative). MAT is predominantly available in the form of opioid agonist treatment with methadone or buprenorphine, with emerging use of opioid antagonist treatments (e.g. extended-release naltrexone). However, there are no recommendations currently available to guide the selection of MAT agent. Moreover, despite substantial evidence for immunomodulatory effects of opioids on immune responses, no studies have employed systems biology methods to evaluate MAT agents for their effects on parameters such as chronic inflammation—particularly important for HIV disease progression and present even in elite controllers or individuals who have achieved virologic control without antiretroviral therapy (ART). To address these questions, Dr. Springer has been awarded a NIDA funded 5 year R01 to evaluate innate immunity and inflammation with her co-PI at Yale School of Medicine, Dr. Shaw, to carry out a prospective, longitudinal study of HIV-positive (on ART) vs. HIV-negative PWIDs starting MAT, recruited from the largest drug treatment center in New Haven, Connecticut. The strength of this proposal is that Dr. Springer is: (1) experienced in HIV and Addiction Medicine; (2) experienced in the novel use of pharmacologic interventions (MAT) to treat SUDs to prevent relapse to opioid and alcohol use as a means to improve HIV viral suppression; (3) has over 15 years experience of conducting NIH-funded research among PLH with SUD and using MAT interventions; and (4) is a co-PI on a successful R01 affiliated with this application that is extending her experience with using systems biology to evaluate MAT on chronic inflammation of HIV infection. As such, the individual, our health care system and society have a high likelihood to benefit – especially on the reduction of HIV within the community.