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）内，导致全国每年有26%的艾滋病毒阳性囚犯被释放到社区。因此，CJS是针对寻求、检测、治疗和保留（STTR）策略以减少社区内艾滋病毒传播的干预措施进行针对性和经验性测试的重要场所。STTR要求最大限度地抑制艾滋病毒，从而降低传染性；HIV阳性囚犯在监禁期间成功地实现了最大程度的抑制。然而，释放后3个月，病毒抑制主要由于阿片类药物复发而丧失——阿片类药物依赖（OD）在全国50%的艾滋病毒阳性囚犯中存在，在东北地区为70-85%。阿片类药物复发与HAART依从性下降、HAART停药和病毒复制环境下艾滋病毒风险行为增加有关——这是艾滋病毒传播的完美风暴。有效治疗吸毒过量阻断了这种关系，并具有改善艾滋病毒结局的巨大潜力；我们的团队使用丁丙诺啡证实了这一益处。阿片类药物替代疗法，特别是美沙酮，由于哲学、安全、监管和人员配备方面的考虑，在CJS中应用有限。因此，检查纳曲酮（NTX）（一种阿片类拮抗剂）的有效性的策略，以提高依从性和保留率，对个人有很大的吸引力，而且还可以减少社区内的艾滋病毒传播。我们的具体目标是对正在向社区过渡的吸毒过量的艾滋病毒阳性囚犯进行一项安慰剂对照随机对照试验。安慰剂对照方法进一步强化了任何应该被证明的发现。将比较纽黑文、哈特福德和斯普林菲尔德的150名CJS受试者的HIV治疗（HIV-1 RNA水平、CD4计数、抗逆转录病毒治疗依从性、护理保留）、药物滥用（阿片类药物使用复发时间、阿片类药物阴性尿百分比、阿片类药物渴望）、不良副作用和HIV风险行为（性和药物相关风险）结果。受试者将按2:1随机分配至d-NTX或d-安慰剂组，为期6个月，并观察12个月。这种治疗方法对CJS有很大的吸引力，因为每月注射很容易，没有转移，副作用很少，而且对其使用没有对抗的哲学担忧。该提案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，将治疗OD作为改善艾滋病毒结果的新方法，在CJS中进行了20多年的研究，并使用d-NTX治疗OD。如果这项d-NTX在释放的HIV+ cjs相关OD人员中的安慰剂对照试验证明其有效性和安全性，则可能成为干预释放HIV+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都很有可能受益——特别是在社区内减少艾滋病毒。

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.