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.

Public Health Relevance

This renewal application for an Independent Investigator K02 award will assist Dr. Springer in continued productive scholarship and increased mentorship of young investigators regarding research involving interventions that will assist in the integrated treatment of persons living with HIV (PLH) and at risk for HIV infection with co-occurring substance use disorders (SUDs) using medication assisted therapies (MAT). Using state of the art systems biology, Dr. Springer with colleagues proposes to study the cellular, gene expression, and biochemical responses to opioid addiction treatment in a group of HIV-positive, compared to HIV-negative adults beginning MAT as her primary affiliated project with this award. She also plans to continue to produce research proposals that will evaluate MAT as HIV prevention in persons with SUDs who are at risk of acquiring HIV and to improve HIV treatment outcomes among those living with HIV. 1

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Development Award - Research (K02)
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Application #
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Flournoy Floyd, Minnjuan Wyncephel
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Budget Start
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Support Year
Fiscal Year
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Indirect Cost
Yale University
Internal Medicine/Medicine
Schools of Medicine
New Haven
United States
Zip Code
Mbaba, Mary; Brown, Shan-Estelle; Wooditch, Alese et al. (2018) Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users under Criminal Justice Supervision. Subst Use Misuse 53:1519-1528
Springer, Sandra A; Di Paola, Angela; Barbour, Russell et al. (2018) Extended-release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living with HIV and Alcohol use Disorders Transitioning to the Community: Results From a Double-Blind, Placebo-Controlled Trial. J Acquir Immune Defic Syndr 79:92-100
Marcus, Ruthanne; Bojko, Martha J; Mazhnaya, Alyona et al. (2018) A qualitative assessment of attitudes about and preferences for extended-release naltrexone, a new pharmacotherapy to treat opioid use disorders in Ukraine. J Subst Abuse Treat 86:86-93
Springer, Sandra A; Di Paola, Angela; Azar, Marwan M et al. (2018) Extended-Release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living With HIV With Opioid Use Disorders Transitioning to the Community: Results of a Double-Blind, Placebo-Controlled Randomized Trial. J Acquir Immune Defic Syndr 78:43-53
Marcus, Ruthanne; Makarenko, Iuliia; Mazhnaya, Alyona et al. (2017) Patient preferences and extended-release naltrexone: A new opportunity to treat opioid use disorders in Ukraine. Drug Alcohol Depend 179:213-219
Vagenas, Panagiotis; Di Paola, Angela; Herme, Maua et al. (2017) Corrigendum to 'An evaluation of hepatic enzyme elevations among HIV-infected released prisoners enrolled in two randomized placebo-controlled trials of extended release naltrexone' [Journal of Substance Abuse Treatment 47 (2014) 35-40]. J Subst Abuse Treat 77:44
Loeliger, Kelsey B; Biggs, Mary L; Young, Rebekah et al. (2017) Gender Differences in HIV Risk Behaviors Among Persons Involved in the U.S. Criminal Justice System and Living with HIV or at Risk for HIV: A ""Seek, Test, Treat, and Retain"" Harmonization Consortium. AIDS Behav 21:2945-2957
Springer, Sandra A; Di Paola, Angela; Azar, Marwan M et al. (2017) Extended-release naltrexone reduces alcohol consumption among released prisoners with HIV disease as they transition to the community. Drug Alcohol Depend 174:158-170
(2016) Erratum to “Correlates of retention on extended-release naltrexone among persons living with HIV infection transitioning to the community from the criminal justice system” [Drug Alcohol Depend. 157 (2015) 158–165] Drug Alcohol Depend 161:372
Springer, Sandra A; Brown, Shan-Estelle; Di Paola, Angela et al. (2015) Correlates of retention on extended-release naltrexone among persons living with HIV infection transitioning to the community from the criminal justice system. Drug Alcohol Depend 157:158-65

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