Naltrexone for Opioid Dependent Released HIV+ Criminal Justice Populations

描述(由申请人提供)：艾滋病毒和药物滥用集中在刑事司法系统(CJS)，导致全国每年26%的艾滋病毒+囚犯被释放到社区。因此，CJS是一个针对并经验性地测试干预措施的重要场所，这些干预措施解决了寻求、检测、治疗和保留(STTR)战略，以减少社区内的艾滋病毒传播。STTR要求最大限度地抑制艾滋病毒，从而减少传染性；艾滋病毒+囚犯在监禁期间成功地实现了最大限度的抑制。然而，在释放后3个月，病毒抑制大部分是由于阿片类药物复发的结果-阿片依赖(OD)在全国50%的HIV+囚犯中存在，在东北部存在70%-85%。在病毒复制的背景下，阿片类药物的复发与HAART依从性的下降、HAART的终止和艾滋病毒危险行为的增加有关--这是艾滋病毒传播的完美风暴。有效治疗药物过量会中断这种关系，并具有改善艾滋病毒结局的巨大潜力；我们的团队已经证实了使用丁丙诺啡的这一益处。由于哲学、安全、监管和人员配备方面的考虑，阿片替代疗法，特别是美沙酮，在CJS中的吸收有限。因此，研究阿片类拮抗剂纳曲酮(NTX)改善依从性和保留率的策略具有巨大的吸引力，不仅有利于个人，还可以减少艾滋病毒在社区内的传播。我们的具体目标是为正在过渡到社区的HIV+吸毒者进行安慰剂控制的NTX(d-NTX)RCT。安慰剂对照方法进一步加强了任何应该得到证实的发现。将在纽黑文、哈特福德和斯普林菲尔德的150名CJS受试者中比较艾滋病毒治疗(艾滋病毒-1RNA水平、CD4计数、ART依从性、护理滞留)、药物滥用(再次使用阿片类药物的时间、阿片类药物阴性尿液百分比、阿片类药物渴求)、不良副作用和艾滋病毒风险行为(性和药物相关风险)结果。受试者将以2：1的比例随机接受d-NTX或d-安慰剂治疗6个月，并观察12个月。这种治疗方法对CJS很有吸引力，因为它每月注射容易，没有分流，副作用很少，而且对其使用没有对立的哲学担忧。这一提议的优势在于，研究人员团队在艾滋病毒、成瘾和CJS方面经验丰富，将药物过量作为改善艾滋病毒结果的一种手段的新用途，在CJS进行了20多年的研究，以及使用d-NTX治疗药物过量的新颖性。如果这项在获释的HIV+CJS患者中进行的d-NTX安慰剂对照试验显示出有效性和安全性，它很可能成为一种干预获释艾滋病毒+囚犯的循证干预措施。因此，个人、我们的医疗保健系统和社会很有可能受益--特别是在社区内减少艾滋病毒方面。

DESCRIPTION (provided by applicant): HIV and drug abuse is concentrated within the criminal justice system (CJS) resulting in 26% of all HIV+ prisoners nationally being released to the community annually. Therefore, the CJS is an important place to target and empirically test interventions that address the Seek, Test, Treat and Retain (STTR) strategy to reduce HIV transmission within the community. STTR requires that HIV is maximally suppressed, resulting in decreased infectiousness; HIV+ prisoners successfully achieve maximal suppression during incarceration. Three 3 months post-release, however, viral suppression is lost mostly as a consequence of relapse to opioids - opioid dependence (OD) is present in 50% of HIV+ prisoners nationally and 70-85% in the Northeast. Opioid relapse is associated with decreased HAART adherence, discontinuation of HAART and increased HIV risk behaviors in the setting of viral replication - the perfect storm for HIV transmission. Effectively treating OD interrupts this relationship and has great potential to improve HIV outcomes; our team has confirmed this benefit using buprenorphine. Opioid substitution therapy, especially methadone, has had limited uptake within the CJS due to philosophical, safety, regulatory and staffing concerns. Therefore, strategies examining the efficacy of naltrexone (NTX), an opioid antagonist, to improve adherence and retention in care, has great appeal to benefit the individual, but also to reduce HIV transmission within the community. Our specific aim is to conduct a placebo-controlled RCT of depot NTX (d-NTX) for HIV+ prisoners with OD who are transitioning to the community. The placebo-control methodology further strengthens any findings that should be demonstrated. HIV treatment (HIV-1 RNA levels, CD4 count, ART adherence, retention in care), substance abuse (time to relapse to opioid use, % opioid negative urines, opioid craving), adverse side effects and HIV risk behavior (sexual and drug-related risks) outcomes will be compared in 150 subjects within CJS in New Haven, Hartford and Springfield. Subjects will be randomized 2:1 to d-NTX or d-placebo for 6 months and observed for 12 months. This therapeutic approach has great appeal by the CJS, given the ease of monthly injections, lack of diversion, few side effects and no antagonistic philosophical concerns about its use. The strength of this proposal is the team of researchers experienced in HIV, addiction and the CJS, the novel use of treating OD as a means to improve HIV outcomes, over 20 years of conducting research in the CJS and the novelty of using d-NTX for the treatment of OD. If this placebo-controlled trial of d-NTX among released HIV+ CJS-involved persons with OD demonstrates efficacy and safety, it is likely to become an evidence-based intervention to intervene with released HIV+ prisoners. 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.