Barriers to Management of HCV: Treating People Who Use Drugs. May 9, 2015

Transcription

1 Barriers to Management of HCV: Treating People Who Use Drugs Alain Litwin, MD, MPH Albert Einstein College of Medicine Montefiore Medical Center May 9, 2015

2 Disclosures Gilead Pharmaceuticals Janssen Pharmaceuticals Merck Pharmaceuticals

3 Outline Background: HCV and persons who use drugs (PWUD) Barriers to scaling up HCV treatment Models of care in drug treatment Peer program Multidisciplinary onsite care Directly observed treatment (DOT) Group treatment

4 Persons Who Inject Drugs (PWID) are at the core of the HCV epidemic People living with HCV infection 1) Hajarizadeh B, et al. Nature Rev Gastroenterol Hepatol ) Grebely J and Dore GJ Antiviral Research In Press.

5 PWID are at the core of the HCV epidemic 80% OF NEW INFECTIONS OCCUR AMONG CURRENT PWID IN MANY COUNTRIES People living with HCV infection 1) Hajarizadeh B, et al. Nature Rev Gastroenterol Hepatol ) Grebely J and Dore GJ Antiviral Research In Press.

6 PWID are at the core of the HCV epidemic 60% OF EXISTING INFECTIONS ARE AMONG CURRENT & FORMER PWID IN MANY COUNTRIES People living with HCV infection 1) Hajarizadeh B, et al. Nature Rev Gastroenterol Hepatol ) Grebely J and Dore GJ Antiviral Research In Press.

7 10 million IDUs worldwide anti-hcv positive Nelson et al., 2011

8 Significance HCV in PWIDs (US) PWIDs are largest group of HCV-infected persons in industrialized countries; ~ 60% in US 1 > 75% of new infections in IDUs Up to 90% of IDUs in methadone clinics have HCV HCV prevalence in noninjecting PWUDs: 2.3%-17% 2 1,100 opiate treatment programs (OTPs) and 290,000 patients in the United States. > 1,000,000 patients have been prescribed buprenorphine in the United States. HCV treatment rates among PWIDs remain low: 1% - 6% 3 1. Shepard et al, Sheinmann et al., Mehta et al., 2007; Grebely et al., 2009

9 Patient Provider Structural There are multi-layered barriers (Mehta) Government / Healthcare system issues Limited accessibility of HCV care locations Limited reimbursement for HCV care Insufficient funds allocated for HCV Overburdened health systems Cost / insurance Segregated service delivery Primary-care provider barriers Knowledge (misconceptions about whom to screen, progression risk, and treatment) Perceptions (may only refer good candidates whom they perceive to need treatment) Workforce issues Inconsistent screening/treatment guidelines Insufficient number of providers who can treat HCV Insufficient resources for case managers, navigators, social workers Specialist barriers Knowledge (some providers may have limited HCV treatment experience) Perceptions (concerns about nonadherence, drug use, relapse, risk of reinfection) General barriers General health care access (primary-care provider, insurance, health literacy, patient-provider relationship) Competing health priorities (mental health, comorbidities) Stability factors (substance use, employment, income, housing, drug treatment, social support HCV-specific barriers Poor knowledge Lack of symptoms Fears about treatment HCV stigma Chronic HCV infection HCV diagnosis Linkage to care Treatment initiation Viral clearance

10 Patient Provider Structural Strategies to overcome barriers (Mehta) Healthcare System Noninvasive disease staging Integrated services HIV & HCV 1 HCV & primary care 2 HCV and opiate substitution 3 Workforce challenges Standard testing & referral guidelines Multidisciplinary team care 4 Telemedicine 5 Primary care & specialist Education at all levels (specialists, ID physicians, HIV providers, primary care) Sensitization to substance use and related comorbidities General barriers Brief interventions (eg, for alcohol use) Incentives Directly observed therapy 6 Peer Navigation 7 Case-management 8 HCV-specific barriers Education & counseling Chronic HCV infection HCV diagnosis Linkage to care Treatment initiation Viral clearance PREVENT 1 Cachay 2013; 2 Evon 2011; 3 Belfori 2007, Krook 2007, Harris 2010, Litwn 2005, Martinez 2012, Mauss 2004, Schaefer , Sylvestre , Treloar 2010; 4 Evon 2011, Sylvestre 2007, Knott 2006, Moussalli 2010; 5 Arora 2010, Hill CROI 2013; 6 Grebely 2007; Evon 2011

11 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 onsite primary care 3,300 patients 59% Latino/a, 23% African American, 18% Caucasian 65% HCV antibody-positive 50% chronic HCV infection

12 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

13 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 current and former drug users have access to treatment for both substance abuse and hepatitis C.

14 Clinic outreach

15 Community outreach

16 Peer advocacy New York State Medicaid 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 illicit drugs can continue to be treated at provider discretion

17 Integrated onsite treatment (n = 73) Retrospective, observational chart review of onsite HCV treatment (peginterferon + ribavirin) provided to 73 drug users between Jan and Dec. 2005: 90% IDU 49% recently used illicit drugs 67% current psychiatric illness 32% HIV-infected 45% SVR Genotype 1: 40% SVR No association between illicit drug use during HCV treatment and virologic outcomes Active illicit drug use during treatment (37%) Litwin et al., JSAT 2009

18 HCV directly observed treatment (DOT) study Litwin et al., BMC ID 2011

19 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) Ribavirin Adherence DOT TAU Peg Adherence DOT TAU TAU = Treatment as usual

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

21 Berg, Arnsten, et al., 2011 HIV DOT decreases viral load

22 Once-daily DOT with PEG/RBV German retrospective study of 49 HCV mono-infected IDUs enrolled in an opiate agonist treatment program with integrated model (methadone or buprenorphine) No recent illicit drug use 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 ribavirin mg All received citalopram (2 weeks prior to HCV treatment) 98% (48 out of 49) achieved SVR Waizmann et al., 2010

23 HIV DOT: association between frequent drug use, treatment arm, and adherence Nahvi et al, DAD 2011

24 Why group treatment? 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 Stein, Soloway et al., JSAT Sylvestre et al; Grebely, Conway et al; McQuaid; Litwin et al.

25 Group treatment in action

26 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 semiprivate 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

27 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 Comanagement of cohort enhances expertise and confidence Multidisciplinary Natural mentoring opportunity Break from the usual

28 Triple therapy with DAAs

29 What about DAAs? Prior studies of onsite HCV treatment SVR = 43% (n = 86) in genotype 1 patients treated with dual therapy (peg + ribavirin) Retrospective chart review of all genotype 1 patients treated onsite with triple therapy (telaprevir or boceprevir) Initiated HCV treatment over 21 month period Between 7/27/2011 and 3/12/2013 (n=50) Litwin et al., EASL Litwin et al., Litwin et al., 2012.

30 Baseline characteristics (n = 50) Characteristic N (%) or Mean +/- SD Age (mean +/- SD) /- 8.7 Race/ethnicity: Hispanic African American Caucasian Illicit drug use (within 6 months): Any Opiates Cocaine Benzos 34 (68) 14 (28) 2 (4) 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: Telaprevir Boceprevir Model of care: Group Individual 42 (84) 8 (16) 38 (76) 12 (24)

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

32 Sofosbuvir: baseline characteristics (n = 102) Characteristic N (%) or Mean +/- SD Age (mean +/- SD) 51 +/- 10 Race/ethnicity: Hispanic African American Caucasian Other 63 (62) 18 (18) 20 (19) 1 (1) Gender: Male 64 (63) HIV-infected 15 (15) Genotype: Regimen: SOF/RBV/PEG SOF/RBV SOF/SIM 68 (67) 17 (16) 16 (16) 1 (1) 24 (23) 62 (61) 16 (16)

33 Sofosbuvir: virologic outcomes (n = 96) Outcome N (%) Early discontinuation (<80%)* 4 (4) 4 weeks: <43 IU/ml 84 (88) 4 weeks: not detected 63 (66) ETR (n = 56) 52 of 56 (93) SVR4 (n = 37) 33 of 37 (89)

34 RCT: intensive models of HCV care for injection drug users (R01 DA034086) Randomize 150 treatment-naive genotype-1 patients to 3 models of onsite care Standard onsite 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

35 Electronic blister packs

36 New DAAs high SVR rates in opiate agonist treatment patients Ledipasvir + sofosbuvir Ombitasvir, paritaprevir/rtv + dasabuvir

37 New DAAs no significant DDIs with opiate agonist medications Ledipasvir + sofosbuvir Ombitasvir, paritaprevir/rtv + dasabuvir

38 0 Cascade of care improves with integrated care Primary care (referral) Primary care (onsite) 154 Treatment Cascade HCV Positive VL Checked Refered Evaluated Offered Rx Started Rx Completed Rx Norton, Steinman, et al Check Hep C

39 Project INSPIRE Montefiore Clinics

40 Meta-analysis of determinants of HCV treatment completion and efficacy in drug users Overall treatment completion: 83% (n = 32 studies) Addiction treatment increased HCV treatment completion. Dimova et al., CID 2012.

41 Meta-analysis of determinants of HCV treatment completion and efficacy in drug users Pooled SVR: 56% (n = 36 studies) SVR affected by genotype 1, 4 and proportion of HIVcoinfected DU. After adjustment, SVR increased with presence of multidisciplinary team. Dimova et al., CID 2012.

42 HCV reinfection rates are low, but further data are needed Aspinall E. CID reinfections/100 person-years post-svr

43 Addiction treatment physicians and HCV treatment eligibility Litwin et al., 2007; NIDA R03 DA16052.

44 HIV providers defer antiviral treatment in active IDUs Westergaard et al., Journal IAS 2012

45 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 NIH Consensus Statement: Treatment of active injection drug use should be considered on a case-by-case basis AASLD Clinical Guidelines: Treatment of HCV infection can be considered for persons even if they currently use illicit drugs NAMD: Exclude use in patients with drug use within the past year.

46 Medicaid restricts HCV treatment for people who use drugs State Abstinence (Months) Urine or serum tox Can active drug users be treated? Illinois 12 Yes No Louisiana 12 Yes No Oregon 6 Unknown No Pennsylvania* 6 Yes No California 6 Yes Yes in drug tx Rhode Island 6 No Yes in drug tx Florida 1 Yes Yes - in drug tx Massachusetts 0 No Yes - in program New York 0 No Yes - not high-risk

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

48 Recommendations for management of HCV infection among people who inject drugs 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) OST = opioid substitution treatment Robaeys et al., CID 2013.

49 Conclusions Barriers to effective HCV care for PWUD can be overcome by onsite treatment, addiction treatment, multidisciplinary teams, and intensive models of care peers, DOT, 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!

50 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, Kim Yu, Brian Edlin, Moonseong Heo, Jennifer Hidalgo, Xuan Li, Benjamin Linas, Bruce Schackman, Meredith Steinman, Linda Agyemang Slides: Jason Grebely and Shruti Mehta

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