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Sandra Ann Springer, MD

Associate Professor of Medicine (AIDS) and Associate Clinical Professor of Nursing; Director, Infectious Disease Outpatient Clinic, Veterans Administration Healthcare Services, Newington

Research Summary

Dr. Springer's has significant clinical research experience with integrating addiction medicine and infectious disease prevention and treatment interventions. She is the Director of InSTRIDE –Integrating Substance Use Treatment Research with Infectious Disease for Everyone https://medicine.yale.edu/lab/springer/ In particular, she has focused on evaluating medication treatments for opioid and alcohol use disorders to improve HIV treatment outcomes among persons with HIV (PWH) released from prison and jail. She currently has an Independent Scientist Award (K02) from NIDA evaluating medications for opioid use disorder (OUD) (MOUD) among PWH. In addition to being a PI on her NIDA-Independent Scientist K02 award, she is currently MPI on 6 grants: (1) a 5 year R01 from NIDA evaluating the impact of medication treatment for opioid use disorder (MOUD) on immunologic outcomes among persons with opioid use disorder (OUD) living with HIV and without HIV infection with colleague Dr. Albert Shaw; (2) a PI on a NIDA funded R33/R61that is evaluating the impact of all forms of MOUD on HIV persistence with colleagues at Yale , Drs. Ya-Chi Ho and Yuval Kluger; (3) the contact PI of a multisite NCATS U01 that is evaluating the integration of infectious disease treatment and OUD treatment with injectable buprenorphine in hospitalized patients with OUD with co-PIs Dr. Edward Nunes, Frances Levin and Kathleen Brady; (4) a co-PI for a VA COOP comparative effectiveness RCT of injectable and sublingual buprenorphine among 900 Veterans with OUD across 20 VA national sites with co-PI Dr. Ismene Petrakis; (5) an MPI on a NIDA JCOIN HEALing award performing a 5 multisite RCT comparing long acting buprenorphine to XR-NTX for persons in prison and jail with OUD with MPIs Dr. Joshua Lee (contact), Lisa Marsch, Robert Schwartz, Elizabeth Waddell and David Farabee; (6) contact PI of a NIDA JCOIN HEALing award that is a hybrid type 1 implementation effectiveness RCT comparing mobile health unit and patient navigation community linkage programs to improve OUD and HIV prevention (PrEP) and treatment (ART) services for persons in prison and jail with co-PIs Drs. Kevin Knight and Ank Nijhawan; (7) and I am a co-I on a NIDA HEALing Communities U01 for persons with OUD in NY state where I co-lead the CJS sub-group (PIs: Drs. Nabila El-Bassel, Edward Nunes, Louisa Gilbert, Daniel Feaster.

Specialized Terms: HIV, HIV prevention, Pre-exposure prophylaxis, PrEP, Opioid use disorder, Medication treatment for Opioid use disorder, buprenorphine, extended-release naltrexone, criminal justice involved persons, persons who use drugs (PWUD), Veterans.

Extensive Research Description

I am fortunate to have had considerable success as an independent investigator starting with early research experiences as an undergraduate at Harvard1-3and during my training as an Infectious Disease Fellow. I have focused my entire research career on developing and evaluating interventions for persons affected by substance use disorders and related infectious diseases, in particular those living with or at risk for HIV; and I have been continuously NIH funded since my NIDA K23 award in 2005. I am considered one of the leaders in clinical research at the intersection ID/HIV and substance use disorders. My work in particular has specifically addressed two intersecting epidemics in this country: the opioid epidemic and the HIV epidemic. My research has shown that medication treatment of opioid use disorder, as well as alcohol use disorder, in persons with HIV improves HIV viral suppression as well as substance use outcomes. This is in line with the goals of the United States Ending the HIV Epidemic (EHE) plan to reduce new HIV infections by 90% by 20304. Most importantly, I have shown that in order to achieve these goals; we must integrate treatment of opioid use disorder (OUD) with medication treatment of OUD (MOUD) (e.g. buprenorphine, methadone, extended-release naltrexone (XR-NTX)) with HIV treatment and prevention services.

During my ID fellowship at Yale, my research identified that persons with HIV who are incarcerated lose viral suppression (VS) within 3 months after release5,6and surmised that relapse to substance use interfered with the HIV care cascade7,8. During my NIDA K23 award that launched my research career I developed the first protocol to use buprenorphine (BPN) as relapse prevention for persons with OUD and HIV transitioning to the community from prison and jail. This pilot study confirmed that BPN was not only well-accepted and tolerated, but it decreased relapse to opioid use and improved HIV VS 6 months after release.9,10 I also evaluated the impact of depression on HIV antiretroviral therapy (ART) adherence among released prisoners with HIV transitioning to the community.11In addition during this time I also created rapid OUD diagnostic tool for non-clinicians called the Rapid Opioid Dependency Screen (RODS)12 that is freely available and is being used by multiple clinical and justice settings to aid in diagnosing OUD. This early body of innovative work was the foundation of my career of continued innovations in integration of treatment of OUD and ID/HIV. After that early BPN pilot project I was awarded two R01s (NIAAA and NIDA) back to back that evaluated the effect of a monthly injectable medication treatment, XR-NTX, in the only ever double blind placebo controlled trials among PWH with AUD and OUD respectively, and both found that XR-NTX achieved and maintained HIV VS 6 months after release from prison and jail.13-18 Further our recent systematic review and meta-analysis of published studies of MOUD on infectious disease outcomes that we just completed also showed that MOUD improves VS19. These innovative studies established that medication treatment of the OUD (and AUD) combined with HIV treatment leads to HIV VS, the goal of treatment of HIV and public health, as it is TREATMENT AS PREVENTION20. Persons living with HIV cannot transmit HIV to uninfected persons if they have VS, thus incorporating MOUD is essential to the goals of the EHE plan.

This early work then led to ground-breaking new collaborations including those within and outside of my discipline to advance further innovative research including: with addiction psychiatrists like Drs. Ned Nunes, Frances Levin & Kathleen Brady on a current innovative research study integrating MOUD into hospital settings in those with concurrent infections related to OUD using long-acting injectable buprenorphine where I am contact PI (NCATS U01TR002763)21; with Dr. Ismene Petrakis at the Veterans Administration in CT where we are co-PIs on the first VA National 20 multisite study comparing two forms of buprenorphine (monthly injectable and daily sublingual) in 900 Veterans with OUD (VA CSP#2014); with basic science researchers evaluating how MOUD affects inflammation and HIV latency with innovative NIH awards as contact PI collaborating with Drs. Albert Shaw (NIDA R01DA043337)22and Ya-Chi Ho & Yuval Kluger (NIDA R61/R33 DA047037)); with implementation scientists (Dr. Nabila El-Bassel) through work on the NY state HEALing communities award (UM1DA049415); with implementation researcher Dr. Kevin Knight and ID specialist Ank Nijhawan on our $11.5 million NIDA U01DA053039 (new JCOIN hub) where I am contact PI, to compare mobile health unit provision of services to patient navigator services for persons who use drugs released from justice settings to link to PrEP/ART and MOUD23, that is also harmonizing with all of JCOIN hubs and HPTN 094 (Steve Shoptaw & Nabila El-Bassel, PIs); with technology researchers working at the interface of OUD like Dr. Sean Young; with public health expert Gregg Gonsalves where we are evaluating the effect of MOUD on VS in Veterans with HIV and OUD; and with addiction medicine specialists like Josh Lee where we are MPIs with Liz Waddell, Robert Schwartz, David Farabee, & Lisa Marsch on a NIDA JCOIN funded RCT (U01DA047982)24comparing injectable buprenorphine to injectable naltrexone in persons in prison and jail. I currently have 10 grants, of which I am PI of 7 of them. Through work collaborating with others in research, clinical work and on national committees, I have been able to more broadly discuss the importance of integration of HIV and addiction prevention and treatment services and translate science into action with policy briefs and changes in national guidelines also.25-30

References:

1. Springer SA, Gastfriend DR. A pilot study of factors associated with resilience to substance abuse in adolescent sons of alcoholic fathers. J Addict Dis. 1995;14(2):53-66.

2. Levin JM, Holman BL, Mendelson JH, et al. Gender differences in cerebral perfusion in cocaine abuse: technetium-99m-HMPAO SPECT study of drug-abusing women. J Nucl Med. 1994;35(12):1902-1909.

3. Teoh SK, Sarnyai Z, Mendelson JH, et al. Cocaine effects on pulsatile secretion of ACTH in men. J Pharmacol Exp Ther. 1994;270(3):1134-1138.

4. Ending the HIV Epidemic : A Plan For America. 2019. https://www.cdc.gov/endhiv/index.html

. Accessed April 10, 2020.

5. Springer SA, Pesanti E, Hodges J, Macura T, Doros G, Altice FL. Effectiveness of antiretroviral therapy among HIV-infected prisoners: reincarceration and the lack of sustained benefit after release to the community. Clin Infect Dis. 2004;38(12):1754-1760.

6. Springer SA, Friedland GH, Doros G, Pesanti E, Altice FL. Antiretroviral treatment regimen outcomes among HIV-infected prisoners. HIV Clin Trials. 2007;8(4):205-212.

7. Springer SA, Spaulding AC, Meyer JP, Altice FL. Public Health Implications for Adequate Transitional Care for HIV-Infected Prisoners: Five Essential Components. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2011;53(5):469-479.

8. Springer SA, Azar MM, Altice FL. HIV, alcohol dependence, and the criminal justice system: a review and call for evidence-based treatment for released prisoners. The American journal of drug and alcohol abuse. 2011;37(1):12-21.

9. Springer S, Chen S, Altice FL. Improved HIV and Substance Abuse Treatment Outcomes For Released HIV-Infected Prisoners: The Impact of Buprenorphine Treatment Journal of Urban Health. 2010.

10. Springer SA, Qiu J, Saber-Tehrani AS, Altice FL. Retention on buprenorphine is associated with high levels of maximal viral suppression among HIV-infected opioid dependent released prisoners. PLoS ONE. 2012;7(5):e38335.

11. Springer SA, Chen S, Altice F. Depression and symptomatic response among HIV-infected drug users enrolled in a randomized controlled trial of directly administered antiretroviral therapy. AIDS Care. 2009;21(8):976-983.

12. Wickersham JA, Azar MM, Cannon CM, Altice FL, Springer SA. Validation of a Brief Measure of Opioid Dependence: The Rapid Opioid Dependence Screen (RODS). J Correct Health Care. 2015;21(1):12-26.

13. Springer SA, Di Paola A, Barbour R, Azar MM, Altice FL. 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. 2018;79(1):92-100.

14. Springer SA, Di Paola A, Azar MM, et al. 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. 2018;78(1):43-53.

15. Di Paola A, Lincoln T, Skiest DJ, Desabrais M, Altice FL, Springer SA. Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for HIV-infected, opioid dependent prisoners and jail detainees who are transitioning to the community. Contemp Clin Trials. 2014;39(2):256-268.

16. Springer SA, Altice FL, Herme M, Di Paola A. Design and methods of a double blind randomized placebo-controlled trial of extended-release naltrexone for alcohol dependent and hazardous drinking prisoners with HIV who are transitioning to the community. Contemp Clin Trials. 2014;37(2):209-218.

17. Springer SA, Brown SE, Di Paola A, Altice FL. 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. 2015;157:158-165.

18. Springer SA, Di Paola A, Azar MM, Barbour R, Krishnan A, Altice FL. Extended-release naltrexone reduces alcohol consumption among released prisoners with HIV disease as they transition to the community. Drug Alcohol Depend. 2017;174:158-170.

19. McNamara K, Biondi BE, Hernandez-Ramirez RU, Taweh N, Grimshaw AA, Springer SA. A Systematic Review and Meta-Analysis of Studies Evaluating the Effect of Medication Treatment for Opioid Use Disorder on Infectious Disease Outcomes. Open Forum Infect Dis. 2021.

20. Springer SA, Larney S, Alam-Mehrjerdi Z, Altice FL, Metzger D, Shoptaw S. Drug Treatment as HIV Prevention Among Women and Girls Who Inject Drugs From a Global Perspective: Progress, Gaps, and Future Directions. J Acquir Immune Defic Syndr. 2015;69 Suppl 1:S155-S161.

21. Seval N, Frank C, Litwin AH, et al. Design and methods of a multi-site randomized controlled trial of an integrated care model of long-acting injectable buprenorphine with infectious disease treatment among persons hospitalized with infections and opioid use disorder. Contemp Clin Trials. 2021;Jun(105).

22. Biondi BE, Mohanty S, Wyk BV, Montgomery RR, Shaw AC, Springer SA. Design and implementation of a prospective cohort study of persons living with and without HIV infection who are initiating medication treatment for opioid use disorder. Contemp Clin Trials Commun. 2021;Jan 6(21).

23. Taweh N, Schlossberg E, Frank C, et al. Linking Criminal Justice-Involved Individuals to HIV, Hepatitis C, and Opioid Use Disorder Prevention and Treatment Services Upon Release to the Community: Progress, Gaps, and Future Directions. International Journal of Drug Policy. 2021.

24. Waddell EN, Springer SA, Marsch L, et al. Long-acting buprenorphine vs. naltrexone opioid treatments in CJS-involved adults (EXIT-CJS). J Subst Abuse Treat. 2021;Apr 8.

25. Springer SA, Korthuis PT, Del Rio C. Integrating Treatment at the Intersection of Opioid Use Disorder and Infectious Disease Epidemics in Medical Settings: A Call for Action After a National Academies of Sciences, Engineering, and Medicine Workshop. Ann Intern Med. 2018;169(5):335-336.

26. Springer SA, Merluzzi AP, Del Rio C. Integrating Responses to the Opioid Use Disorder and Infectious Disease Epidemics: A Report From the National Academies of Sciences, Engineering, and Medicine. JAMA.2020.

27. Seval N, Eaton E, Springer SA. Beyond Antibiotics: A Practical Guide for the Infectious Disease Physician to Treat Opioid Use Disorder in the Setting of Associated Infectious Diseases. Open Forum Infect Dis. 2020;7(1):ofz539.

28. Springer SA, Barocas JA, Wurcel A, et al. Federal and State Action Needed to End the Infectious Complications of Illicit Drug Use in the United States: IDSA and HIVMA’s Advocacy Agenda. Journal of Infectious Diseases. 2020;222(Suppl 5):S230-238.

29. Springer SA, Biondi BE, Frank C, El-Bassel N. A Call to Action to Combat the Opioid Epidemic among Women. J Addict Med. 2020.

30. Serota DP, Barocas JA, Springer SA. Infectious complications of addiction: A call for a new subspecialty within infectious diseases. Cain Infect Dis. 2019.

Coauthors

Research Interests

Acquired Immunodeficiency Syndrome; Alcoholism; Buprenorphine; HIV; Naltrexone; Opioid-Related Disorders; Prisoners; Risk-Taking; Randomized Controlled Trial; Substance-Related Disorders; Pre-Exposure Prophylaxis; Addiction Medicine

Public Health Interests

Behavioral Health; Clinical Trials; HIV/AIDS; Infectious Diseases; Substance Use, Addiction; Pharmaceuticals and Medical Devices

Selected Publications

Clinical Trials