This is an independent scientist award to assist in the continued research of Dr. Sandra Springer, who focuses her research on interventions that will improve linkages to care for HIV+ criminal justice populations (CJS) with co-morbid substance use disorders who are transitioning to the community. This award will also increase her time to devote towards mentoring young investigators who share this interest. HIV and drug abuse is concentrated within the CJS, therefore, it is an important place to target and empirically test interventions that address strategies to reduce HIV transmission within the community. When HIV is maximally suppressed decreased infectiousness is the result. HIV+ prisoners successfully achieve suppression during incarceration, however 3 months post-release viral suppression is lost, mostly due to relapse to drugs and alcohol. Opioid dependence (OD) and alcohol dependence (AD) are present in 50-70% of HIV+ prisoners nationally. Relapse to substance use is associated with discontinuation of HAART adherence and increased HIV risk behaviors, the perfect storm for HIV transmission. Effectively treating OD and AD interrupts this relationship and has great potential to improve HIV outcomes. Opioid substitution therapy, especially methadone, has had limited uptake within the CJS due to philosophical, safety, regulatory and staffing concerns. Similarly, pharmacologic interventions to target treatment of AD are essentially nonexistent within the CJS. Therefore, strategies examining the efficacy of naltrexone (NTX), an opioid antagonist approved by the FDA for treatment of both OD and AD, to improve adherence and retention in care, has great appeal to benefit the individual and to reduce HIV transmission within the community. Dr. Springer has been awarded 2 R01s (Project 1, NIDA R01 DA030762;and Project 2, R01 AA018944) that serve as the research platform for this independent scientist award. The specific aim of both studies is to conduct a placebo-controlled RCT of extended-release NTX (XR- NTX) for HIV+ prisoners with OD (project 1) and AD (project 2) who are transitioning to the community. The placebo-control methodology further strengthens any findings that should be demonstrated. HIV treatment, substance abuse, adverse side effects and HIV risk behavior outcomes will be compared in subjects within CJS in New Haven, Hartford and Springfield. 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 that Dr. Springer is experienced in HIV, addiction and the CJS;the novel use of pharmacologic interventions to prevent relapse to OD and AD as a means to improve HIV outcomes;over 7 years of conducting research in the CJS;and the novelty of using XR-NTX for the treatment of OD and AD. These trials may demonstrate efficacy and safety, and then XR-NTX is likely to become an evidence-based intervention 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. PUBLIC HEALTH RELEVANCE: This award will assist in increasing mentorship of young investigators who are interested in a research career involving interventions that will assist in treatment of HIV+ CJS populations with co-occurring substance use disorders. Using randomized, placebo-controlled trials, HIV treatment, opioid and alcohol treatment and HIV risk behavior outcomes are examined among HIV-infected prisoners with opioid dependence and alcohol dependence who are treated with extended-release naltrexone (XR-NTX) as they are transitioning from the correctional to the community setting. The public health relevance is that outcomes from these studies will establish the efficacy, safety and tolerability of pharmacological therapy using XR-NTX treatment among HIV+ persons within the CJS and establish XR-NTX treatment as an effective, evidence-based treatment for opioid and alcohol dependence for released HIV+ prisoners - a population who shares a disproportionate burden of morbidity and mortality and has fared poorly using the existing standard of care. 1