Intensive Models of HCV Care for People Who Inject Drugs

Intensive Models of HCV Care for People Who Inject Drugs Alain Litwin, MD, MPH Professor of Medicine Albert Einstein College of Medicine Montefiore Medical Center June 20, 2015

Disclosures Gilead Sciences Janssen Pharmaceuticals Merck Pharmaceuticals

Outline Models of HCV Care for PWID Peer Program Multidisciplinary On-site Care Directly Observed Treatment (DOT) Group Treatment Key factors to consider when treating PWID Future Directions

Integrating HCV Care with Opiate Agonist Treatment Albert Einstein College of Medicine / Montefiore Medical Center Network of community-sited opiate agonist treatment programs in the Bronx, NY Comprehensive on-site primary care 3300 patients 59% Latino/a, 23% African American, 18% Caucasian 65% HCV Antibody positive 50% chronic HCV infection

Clinic Locations New Jersey The Bronx 3 1 Key 1: Melrose Wellness Center 2: Port Morris Wellness Center 3: Waters Place Wellness Center 4 Manhattan 2

Roots of Peer Program We represent a coalition of patients, providers, family members and friends: all affected by the hepatitis C epidemic in our South Bronx Community. People in methadone maintenance must have access to hepatitis C resources. We work to ensure that people who use drugs have access to treatment for both substance abuse and hepatitis C.

Clinic Outreach

Community Outreach

Peer Advocacy New York State Medicaid (Roose et al, 2014) 2003: HCV Viral load and Genotype tests covered by Medicaid 2013: Prohibited mandatory mail order pharmacies for HIV and HCV medications 2014: People who use drugs can continue to be treated at provider discretion

Integrated On-Site Treatment (n=73) (Litwin et al, 2009) Retrospective, observational chart review of on-site HCV treatment (pegylated interferon and ribavirin) provided to 73 drug users between January, 2003 and December, 2005: 90% PWID 49% recently used drugs 67% current psychiatric illness 32% HIV-infected 45% SVR genotype 1 40% SVR No association between drug use during HCV treatment and virologic outcomes Active illicit drug use during treatment (37%)

HCV Directly Observed Treatment (DOT) Study (Litwin et al, 2011)

Adherence increased in DOT arm (n=40) Over 24 weeks, pill count adherence 88% DOT vs. 77% TAU (p=0.02) All administered peg, adherence 96% DOT vs. 94% TAU (p=ns) 100 100 95 95 90 90 85 85 80 75 70 65 60 55 50 Ribavirin Adherence DOT TAU 80 75 70 65 60 55 50 Peg Adherence DOT TAU

Treatment Outcomes (n=80) Outcomes DOT TAU <12 weeks 3 (8%) 8 (20%) ETR 28 (70%) 27 (68%) SVR12 22 (55%) 20 (50%)

HIV DOT Decreases Viral Load (Berg, Arnsten et al, 2011)

HIV DOT: Association between frequent drug use, treatment arm, and adherence (Nahvi et al, 2011)

Why Group Treatment? (Stein, Soloway et al, 2012) Historic role of HCV support group at Einstein Support groups familiar in addiction treatment Synergy with participation of medical provider Address patient and provider barriers to treatment Builds on other models of group-based treatment (Sylvestre et al; Grebely, Conway et al; McQuaid; Litwin et al)

Group Treatment in Action

HCV Group Treatment Model Health Educator / Peer Sets up room: coffee, snacks Side effect and depression surveys Weights taken Group discussion cofacilitated by Health Educator and Peer Provider Conducts semi-private individual visits Vitals and focused physical Addresses adverse effects and adherence Administers peg interferon injections and growth factors as needed Answer group questions Conclude with patient milestones, updates and peer-led meditation

Group Treatment Benefits For Patients Social support is built-in Misconceptions addressed Reassurance by concurrent participation of peers fear of side effects Directly administered peg Weekly oral meds dispensed Fatty food snacks provided Support for recovery Upward spiral For Providers Frequent contact: providers and peers Co-management of cohort enhances expertise and confidence Multidisciplinary Natural mentoring opportunity Break from the usual

Triple Therapy with DAAs

What about Direct Acting Antiviral Agents? (Litwin et al, 2015) Prior studies of on-site HCV treatment (Litwin et al, 2009; Litwin et al, 2012) SVR=43% (n=86) in genotype-1 patients treated with dual therapy (peg + ribavirin) Retrospective chart review of all genotype-1 patients treated on-site with triple therapy (either telaprevir or boceprevir) Initiated HCV treatment over 21 month period Between 7/27/2011 and 3/12/2013 (n=50)

Baseline Characteristics (n=50) Characteristic N (%) or Mean +/- SD Age (mean +/- SD) 49.4 +/- 8.7 Race/ethnicity: Hispanic African American Caucasian 34 (68) 14 (28) 2 (4) Illicit drug use (within 6 months): Any Opiates Cocaine Benzos 25 (50) 13 (26) 16 (32) 11 (22) Opiate agonist treatment: Methadone Buprenorphine None 39 (78) 7 (14) 4 (8) Current psychiatric illness 43 (86) Protease inhibitor: Model of Care: Telaprevir Boceprevir Group Individual 42 (84) 8 (16) 38 (76) 12 (24)

Results and Virologic Outcomes (n=50) Characteristic N (%) Illicit drug use (during tx): Any (n=49) Opiates Cocaine Benzos 22 (45) 13 (27) 13 (27) 8 (16) Early discontinuation (non-virologic) 6 (12) ETR 35 (70) SVR12 31 (62)

Electronic Blister Packs

Sofosbuvir Treatment Outcomes SOF/PEG/RBV and SOF/RBV (n=95) Characteristic N (%) or Mean Age (mean) 51 Gender: Male 63 (67) Genotype: 1 2 3 4 Regimen: SVR12: SOF/PEG/RBV SOF/RBV Overall G1 (SOF/PEG/RBV) G1 (SOF/RBV) G2 (SOF/RBV) G3 (SOF/RBV) G4 (SOF/RBV) 57 (60) 16 (17) 21 (22) 1 (1) 23(23) 72 (61) 72 of 85 (85) 22 of 23 (96) 27 of 34 (79) 11 of 14 (79) 12 of 13 (92) 0 of 1 (0)

Combination DAA Regimens Baseline Characteristics (n = 87) Characteristic Age (mean +/- SD) 51 +/- 10 Gender: Male 56 (64) Genotype: 1 4 Regimen: LDV/SOF SIM/SOF 3D + RBV N (%) or Mean +/- SD 86 (99) 1 (1) 56 (64) 30 (35) 1 (1)

Combination DAA Regimens Outcomes (n=87) Outcome N (%) Early discontinuation (<80%) 0 (0) 4 weeks: <15 IU/ml (n=79) 79 of 79 (100) 4 weeks: not detected (n=79) 77 of 79 (97) ETR (n=58) 58 of 58 (100) SVR4 (n=46)* 46 of 46 (100)

Outcomes at CHCC 250 200 150 176 Chronic HCV 86% 83% PWID Cascade 47% on opioid of Care agonist treatment 25% actively using drugs 34% were cirrhotic 17% were HIV coinfected. 229 HCV AB+ 214 VL Drawn (94% of all Ab+'s) 176 VL+ (82% of all VL's drawn) 100 53% Cure rates: 97% 152 Evaluated (86% of all VL+'s) 80 Started Tx (46% of all VL+'s) 50 63 Finished Tx (36% of all VL+'s); 17 projected 52 SVR (30% of all VL+'s); 28 projected 0 229 HCV AB+ 214 VL 176 VL+ Drawn (94% (82% of all of all Ab+'s) VL's drawn) 152 Evaluated (86% of all VL+'s) 80 Started 63 Finished Tx (46% of Tx (36% of all VL+'s) all VL+'s); 17 projected 52 SVR (30% of all VL+'s); 28 projected

70% 60% 64% P=0.004 Retained in buprenorphine treatment > 6 mos Not retained in buprenorphine treatment 50% 51% P=0.04 40% 30% 31% 31% P=0.02 27% 20% 10% 12% 8% 8% P=0.2 0% Referred Evaluated Offered treatment Initiated treatment

Project INSPIRE Montefiore Primary Care Clinics HCV Champions Care Coordinators

Key Factors On-site HCV evaluation and treatment Collaboration with peers Multidisciplinary team Care coordinator, patient navigator, pharmacist, and/or nurse SVR with multidisciplinary team (Dimova et al) Collaboration with harm reduction programs Opiate agonist treatment (methadone & buprenorphine) HCV treatment completion with addiction treatment (Dimova et al) Patients cycle in and out of opiate agonist treatment Intersection with criminal justice system Collaboration with housing and mental health services Coordination with hospitalization, detox, and rehab

People who use drugs are once again being categorically excluded from HCV treatment 1997 NIH Consensus Statement: Treatment of patients who are actively using illicit drugs should be delayed until these habits are discontinued for at least 6 months. 2002 NIH Consensus Statement: Treatment of active injection drug use should be considered on a case-by-case basis. 2004 AASLD Clinical Guidelines: Treatment of HCV infection can be considered for persons even if they currently use illicit drugs. 2014 NAMD: Exclude use in patients with drug use within the past year.

From: Restrictions for Medicaid Reimbursement of Sofosbuvir for the Treatment of Hepatitis C Virus Infection in the United StatesMedicaid Restrictions of Sofosbuvir for Hepatitis C Ann Intern Med. Published online June 30, 2015. doi:10.7326/m15-0406 Figure Legend: Medicaid reimbursement criteria for sofosbuvir based on the required period of abstinence from drug and alcohol use. Date of download: 7/15/2015 Copyright American College of Physicians. All rights reserved.

Patient Centered Models for HCV Care for PWID Multi-site national study: NYC, Providence, Baltimore, Boston, Cincinnati, Seattle, San Francisco, Albuquerque RCT: Patient Navigation (and Peer Support) versus Directly Observed Treatment (DOT) 1000 PWID: 600 initiating treatment Actively injecting drugs within last 3 months Recruitment from community sites (e.g. harm reduction programs) On-site HCV treatment at CHCs and methadone programs DOT at methadone programs / CHCs and within community by community health workers Standardized education: HCV overview (before treatment) and Prevention/Reinfection (end of treatment) Outcomes: initiation, adherence, completion, SVR, resistance, and reinfection LDV/SOF to be provided by Gilead Sciences

Intervention Targeted at Multiple Levels (Mehta)

Acknowledgements HCV Clinical Team: Valerie Bartlett, Sarah Church, Michael Ciofoletti, Lauren Cockerham-Colas, Joe Hecht, Cori Langert, Karen Jefferson, Giliane Joseph, Steven Puente, Sheila Reynoso, Irene Soloway, Melissa Stein, Peter Tenore, Jordan Wong, Joyce Wong HCV Research Team: Julia Arnsten, Brianna Norton, Chinazo Cunningham, Kim Yu, Moonseong Heo, Jennifer Hidalgo, Galina Umanski, Kaira Lora, Meredith Steinman, Linda Agyemang Slides: Shruti Mehta

Acknowledgements New York State Department of Health New York City Department of Health and Mental Hygiene National Institute of Drug Abuse R03 DA16052 K23 DA022454 R01 DA034086 Robert Wood Johnson Foundation Center for Medicare and Medicaid Services Vertex Pharmaceuticals Gilead Sciences Merck Pharmaceuticals

Additional Slides

RCT: Intensive Models of HCV Care for Injection Drug Users (R01 DA034086) Randomize 150 treatment-naive genotype-1 patients to three models of on-site care Standard on-site care Directly Observed Treatment Group Treatment Outcomes: Adherence, completion, SVR, and resistance Adherence measured by electronic blister packs What levels of adherence prevent resistance? Cost and cost-effectiveness of each model

Once Daily DOT with PEG/RBV (Waizmann et al, 2010) German retrospective study of 49 HCV mono-infected IDUs enrolled in an opiate agonist treatment program with integrated model (methadone or buprenorphine) 57% genotypes 2 / 3; 43% genotypes 1 / 4 Median age 30 years median BMI 24 median HCV viral load = 121,775 IU/ml HIV-negative Patients seen once daily: DOT with PEG-IFN alfa-2a once weekly and daily fixed dose of ribavirin 800 mg 1200 mg. All received citalopram (2 weeks prior to HCV treatment) 98% achieved SVR (48 out of 49)

Cascade of Care Improves with Integrated Care (Norton, Steinman, et al Check Hep C) Primary Care (Referral) Primary Care (On-site) 154 Treatment Cascade 122 67 45 17 6 4 Positive VL Checked Refered Evaluated Offered Rx Started Rx Completed Rx

Determinants of HCV Treatment Completion and Efficacy in Drug Users Assessed by Meta-analysis (Dimova et al, CID 2012) Overall treatment completion = 83% (n=32 studies) Addiction treatment increased HCV treatment completion.

Determinants of HCV Treatment Completion and Efficacy in Drug Users Assessed by Meta-analysis (Dimova et al, CID 2012) Pooled SVR = 56% (n=36 studies) SVR affected by genotype 1/4 and proportion of HIV coinfected DU. - After adjustment, SVR increased with presence of multidisciplinary team.

HCV reinfection rates are low, but further data are needed 2.4 reinfections/100 person years post SVR Aspinall E. Clinical Infectious Diseases 2013.

HIV Providers Defer Antiviral Treatment in Active IDUs (Westergaard et al, Journal IAS 2012)

First global recommendations for HCV among PWID Robaeys G*, Grebely J*, et al. Clinical Infectious Diseases 2013

Recommendations for the Management of Hepatitis C Virus Infection Among People Who Inject Drugs (Robaeys et al, CID 2013) REVISED in 2015 HCV treatment can be considered for PWID, provided they wish to receive treatment and are able and willing to maintain regular appointments. (A1) A history of IDU and recent drug use at treatment initiation are not associated with reduced SVR, and decisions to treat must be made on a case-by-case basis. (B1) HCV Treatment for PWID should be considered on an individualized basis and delivered within a multidisciplinary team setting. (B1) Access to harm reduction programs, social work, and social support services should be a component of HCV clinical management. (B2) PWID should not be excluded from HCV treatment on the basis of perceived risk of reinfection. (B1) OST is not a contraindication for liver transplantation, and individuals on OST should not be advised to reduce or stop therapy. (A1)

Patient Centered Models for HCV Care for PWID Aim 1: to determine whether Patient Navigation or Directly Observed Therapy provided on-site to active PWID at methadone programs and community health centers is more effective for enhancing: HCV treatment initiation Adherence (measured by electronic blister packs) Treatment completion SVR12 Resistance Aim 2: to determine the incidence and factors associated with development of drug resistance and reinfection in PWID initiating HCV treatment. Aim 3: to understand factors associated with key study outcomes (e.g. reinfection) using mixed research methods.

Conclusions Barriers to effective HCV care for PWID can be overcome by on-site treatment, addiction treatment, multidisciplinary teams and intensive models of care - peers, directly observed treatment, and group treatment. Barriers to HCV care are greater than ever and will limit scaling up of treatment. Advocacy is urgently needed to increase access to care and promote social justice!