Mental Health, Substance Use, and HIV/HCV coinfection treatment

1. Mental Health, Substance Use, and HIV/HCV coinfection treatment Jeffrey J. Weiss, PhD Assistant Professor, Psychiatry Mount Sinai School of Medicine New York, New York, USA

2. Co-Occurrence of HIV, HCV, Mental Health & Substance Use Problems Mental Health HCV HIV Substance Use (IDU)

3. POVERTY • DRUG ADDICTION • INJECTING DRUG USE • MENTAL HEALTH PROBLEMS • HISTORY OF INCARCERATION • METHADONE MAINTENANCE • SEXUAL ORIENTATION • HOUSING INSTABILITY • RACIAL/ETHNIC MINORITY • UNEMPLOYMENT

4. Continuum of HCV Care for HIV/HCV Coinfected Persons • Identification of HCV infection • Engagement in HCV Care • Knowledge about HCV infection and treatment – how it differs from HIV • Preparation for HCV Treatment • HCV Treatment • Prevention of Reinfection if SVR

5. HCV Neuropsychiatric Context There are high rates of current/past psychiatric and substance use disorders (IDU) in the population of HIV/HCV coinfected persons medically eligible for HCV treatment PEG-IFN/RBV causes neuropsychiatric symptoms (depression, anxiety, emotional lability, irritability, insomnia) in a high percentage of treated patients and can result in dose reductions and early treatment discontinuation.

6. Fatigue and weakness(65-66%) Headaches (43-62%) Body, muscle, joint aches (40-56%) Irritibility, anxiety (33-47%) Insomnia (30-40%) Neutropenia (26-27%) Loss of appetite (24-32%) Anemia (22%) Depression (20-31%) Concentration Problems (10-17%) Common Side Effects of HCV Therapy

7. Flulikesymptoms Fatigue Severity Depressive/ anxietysymptoms 0 1 2 3 4 5 6 7 8 9 10 11 12 IFN Treatment (Weeks) Time Course of IFN Side Effects KR Reddy, MD, HIV-HCV co-infection preceptorship programme, New York, 19-20 May 2005

8. Hepatitis C Patients’ Self-reported Adherence to Pegylated Interferon and Ribavirin In a sample of 180 patients on treatment for Hepatitis C (23% co-infected with HIV):  7% reported missing at least one injection of pegylated interferon in the last four weeks  21% reported missing at least one dose of ribavirin in the last 7 days When non-adherence was defined as taking <80% of either interferon or ribavirin, 13% of the co-infected patients were non-adherent compared to 5% of the mono-infected (OR: 2.8; 95% CI: 0.8–9.3; p = 0.09) Weiss et al. (2008) Alimentary Pharmacology & Therapeutics

9. The HCV Treatment Pipeline . . . HCV Polymerase and Protease Enzyme Inhibitors Drug resistance has not been a problem in HCV therapy; it may become a problem with new generation treatment Dosing every 8 hours with food will likely be required with some new agents (e.g., Telaprevir [VX-950]) The importance of adherence will likely increase in HCV treatment Providers may become more selective of who to treat for HCV due to potential development of resistant virus.

10. Determinants of HCV Treatment Adherence Prospective study of HCV-treatment naïve patients beginning PEG-IFN/RBV Mental Health, Substance Use, Cognitive assessments at Baseline, 12 weeks, 24 weeks on treatment Medical record followed to 6 months after end of treatment

11. Subject Demographics (N=24) GenderMale 88% Age Mean Years (range) 49 (20-73) Race white 42% hispanic 33% black 25% ROT IDU 67% Sexual 13% Intranasal Cocaine 8% Transfusion 8% Perinatal 4% Site of Care Coinfection Clinic 50% Private Physician 33% Veterans Hospital 17%

12. Treatment Discontinuation by week 24(11/24 = 46%) Week Reason Decision 2 Side effects Patient 4 Renal problems Provider 5 Rash/Lack of Response Both 5 Panic attacks Provider 8 Side effects Patient 10 Anemia Provider 12 Anemia Provider 16 Lack of Response Provider 20 Pneumonia Provider 24 Lack of Response Provider 24 Lack of Response Provider

13. Psychiatric/Substance Use Baseline (N=24) 20/24 with at least one lifetime substance use disorder 15/24 with at least one lifetime psychiatric disorder 0/24 meet current criteria for at least one substance use disorder 6/24 meet current criteria for at least one psychiatric disorder 5/24 currently on methadone maintenance 8/24 currently on psychotropic medication

14. Prophylactic use of psychotropics? • 13/24 with a history of psychiatric or substance use disorder not on any psychotropic medication at time of treatment initiation  5/13 discontinued treatment by week 24  5/13 did not need any psychotropic medication by week 24 of HCV treatment  3/13 needed to begin psychotropic medication during HCV treatment and remained on treatment

15. Pre-HCV treatment psychiatric management • All patients are referred for psychiatric evaluation of current functioning prior to beginning HCV treatment • If no current symptoms/disorders, monitor closely (no empirical evidence for antidepressant prophylaxis) – follow-up with evaluator by week 2 of treatment • If current symptoms/disorders, treat and stabilize prior to beginning HCV treatment; monitor closely during treatment

16. Does self-injecting interferon ever bring back memories or feelings about your former injecting drug use? (n=16) • 13/16 (81%) – ‘No’ • ‘When I see the needle, I get flashbacks of injecting myself. I remember it and the bad things it did to me. It is not bad or good; having the nurse give me the injection at the clinic is a good thing.’ • ‘Yes, it brings back memories.’ • ‘Thinking about using IV drugs – the need to inject to sustain myself.’

17. Some people say that the side effects of interferon remind them of drug withdrawal. Have you felt this way? (n=16) • 13/16 (81%) – ‘No’ • ‘Yes – my bones hurt; the monkey on your back, doesn't bring desire to use drugs though.’ • ‘In the beginning it did, but I didn't think of it that way until you just asked.’ • ‘It did remind me of withdrawal; that made it harder to deal with.’

18. Are providers more stringent in treating coinfected for HCV? • Higher prevalence of current depression, psychiatric and substance use disorders among HCV-monoinfected than HIV/HCV-coinfected patients at time of HCV treatment initiation. • No differences in engagement in psychiatric treatment between HCV-monoinfected and HIV/HCV-coinfected. • One explanation for difference is that providers are using more stringent criteria to psychiatrically screen HIV/HCV-coinfected patients for treatment. Weiss, Bräu, Dieterich, Fishbein: Poster WEPE0175 at AIDS 2008

19. Two large European cohort studies of HCV-monoinfected find that IDU (including active use) does not necessarily decrease: Adherence to HCV treatment Outcome of HCV treatment – SVRContext of adequate access to food, housing, medical care, medication, psychiatric care, syringe exchange, opioid substitution therapy. Robaeys et al. (2006) Eur J Gastroenterol Hepatol (Benelux) Bruggman et al. (2008) J Viral Hepatitis (Switzerland)

20. Acknowledgments MentorsColleaguesProject Staff David Bangsberg, MD Damaris Carriero, MS, ANP-C Samia Ahmed, MD Norbert Bräu, MD Dawn Fishbein, MD Katherine Barboza, MA Doug Dieterich, MD Juanita Jones, MPH, RPA-C Cory Head, MA Brian Edlin, MD Viktoriya Khaitova,, RPA-C Diana Lin, MPH Susan Essock, PhD David Motamed, RPA-C Georgina Osorio, MD Scott Friedman, MD Elizabeth Ryan, PhD Mario Velez, BS Jack Gorman, MD Alicia Stivala, NP Danielle Wolman, MSW Sue Marcus, PhD Tracy Swan Susan Morgello, MD Diane Tider, MPH Alison Uriel, MBBS Glenn Wagner, PhD

21. Grant Support Supported by Grant Number K23MH071177 from the National Institute of Mental Health. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.