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26%的艾滋病毒+囚犯每年被释放到社区。因此，CJS是一个重要的地方，有针对性和经验测试干预措施，解决寻找，测试，治疗和保留（STTR）战略，以减少艾滋病毒在社区内的传播。STTR要求最大限度地抑制艾滋病毒，从而降低传染性;艾滋病毒阳性囚犯在监禁期间成功地实现了最大限度的抑制。然而，释放后三个月，病毒抑制主要是由于阿片类药物复发而失去的-全国50%的艾滋病毒+囚犯和东北部70-85%的囚犯存在阿片类药物依赖（OD）。阿片类药物复发与HAART依从性降低、HAART中止和病毒复制背景下HIV风险行为增加相关-这是HIV传播的完美风暴。有效治疗OD中断了这种关系，并有很大的潜力改善艾滋病毒的结果;我们的团队已经证实了使用丁丙诺啡的好处。阿片类药物替代疗法，特别是美沙酮，由于哲学，安全性，监管和人员配置方面的问题，在CJS中的吸收有限。因此，研究阿片类拮抗剂纳洛酮（NTX）的疗效以提高护理依从性和保留率的策略，不仅对个人有益，而且对减少社区内的艾滋病毒传播具有极大的吸引力。我们的具体目标是对正在过渡到社区的艾滋病毒+OD囚犯进行长效NTX（d-NTX）的安慰剂对照RCT。安慰剂对照方法进一步加强了应证明的任何结果。将在纽黑文、哈特福德和斯普林菲尔德的CJS内的150例受试者中比较HIV治疗（HIV-1 RNA水平、CD 4计数、ART依从性、护理保留）、物质滥用（至阿片类药物使用复发的时间、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HIV风险行为（性和药物相关风险）结局。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，而且没有对抗性的哲学问题。该提案的优势在于在艾滋病毒，成瘾和CJS方面经验丰富的研究人员团队，治疗OD作为改善艾滋病毒结果的一种手段的新用途，在CJS进行研究超过20年，以及使用d-NTX治疗OD的新奇。如果在释放的HIV+ CJS参与的OD患者中进行的d-NTX安慰剂对照试验证明了有效性和安全性，则很可能成为对释放的HIV+囚犯进行干预的循证干预。因此，个人、我们的卫生保健系统和社会都很有可能受益，特别是在减少社区内的艾滋病毒方面。

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.