New treatments for the infectious complications of substance use disorders, and the barriers to implementation.

New treatments for the infectious complications of substance use disorders, and barriers to implementation.

Benjamin BearnotNovember 10, 2015

DisclosuresNo conflicts to report

OutlineScope of Substance Use Disorder New treatments for Hepatitis C + barriersNew treatments for Skin and Skin Structure Infections (Cellulitis) + barriers2 Cases

Scope of the Problem

Case and Deaton, PNAS 2015All-cause mortality, ages 4554 for US White non-Hispanics (USW), US Hispanics (USH), and six comparison countries: France (FRA), Germany (GER), the United Kingdom (UK), Canada (CAN), Australia (AUS), and Sweden (SWE).

Scope of the Problem

Case and Deaton, PNAS 2015

Opioids of MisuseCicero et al, NEJM 2015

HCV Epidemiology

* Includes cases contracted in the hospital or during childbirthSource: Centers for Disease Control and PreventionSexual 17%Unknown 10%Past transfusion 3%Occupational 4%

Other 9%*Injection drug use 57%Holmberg et al,NEJM 2013

*incidence and reported case numbers differ from true values and are influenced by incr screening (incr baby boomer screening, effected by better treatment, and incr reported)

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HCV Epidemiology Cont.

Suryaprasad, CID 2014

Genotype 1OptionsDurationSVR for tx nave ptsSVR for tx experienced or cirrhotic ptsCostSide EffectsHarvoni (Sofosbuvir / Ledipasvir)

8 wks (no cirrhosis, low VL)12 wks (high VL)24 wks (cirrhosis)98-99%97% (24 wks)$94,500Fatigue (18%)Headache (17%)Nausea (9%)Diarrhea (7%)Insomnia (6%)

Viekira Pak(Peritaprevir / Ombitasvir / Dasabuvir / Ribavirin)

12 wks (no cirrhosis)24 wks (cirrhosis)97%95% (24 wks)$83,319Fatigue (34%)Nausea (22%)Pruritus (18%)Insomnia (14%)Asthenia (14%)Daclatasvir/ Sofosbuvir

12 wks (no cirrhosis)24 wks (cirrhosis)96%76-100% (24 wks)$63,000 (12 wks)Fatigue (14%)Headache (14%)Nausea (8%)Diarrhea (5%)

Table design concept from: Dr. Richard Colvin (personal communication).

Genotype 2OptionsDurationSVR for tx nave ptsSVR for tx experienced or cirrhotic ptsCostSide EffectsSofosbuvir / Ribavirin

12 wks (no cirrhosis)16 wks (cirrhosis)

92-98%91-96%$86,000 (12 wks)Fatigue (36%)Headache (25%)Nausea (18%)Insomnia (12%)Anemia (8%)

Daclatasvir/ Sofosbuvir

12 wks (w/ or w/out cirrhosis)>95%>95%$63,000Fatigue (14%)Headache (14%)Nausea (8%)Diarrhea (5%)

Genotype 3OptionsDurationSVR for tx nave ptsSVR for tx experienced or cirrhotic ptsCostSide EffectsSofosbuvir / Ribavirin / Peginterferon12 wks97%87%$94,000Fatigue (59%)Headache (36%)Nausea (34%)Insomnia (25%)Anemia (21%)Anorexia (18%)Neutropenia (17%)Flu-like sx (16%)Irritability (13%)Sofosbuvir / Ribavirin

24 wks93%77% (tx experienced)92% (cirrhosis, tx nave)$169,000Fatigue (36%)Headache (25%)Nausea (18%)Insomnia (12%)Anemia (8%)

Daclatasvir/ Sofosbuvir

12 wks (no cirrhosis)24 wks (cirrhosis)97%88%$63,000 (12 wks)Fatigue (14%)Headache (14%)Nausea (8%)Diarrhea (5%)

HCV Treatment in Primary Care Setting

MMWR 2014 update, ongoing implementation, with ~30% on tx with DAAs

Arora , NEJM 2011

HCV Treatment in Primary Care SettingSystematic review in British Journal of General Practice, December 201312 papers related to the mainstream PC setting, 3 to treatment provision in the prison, and 1 to both mainstream PC and prisons.

Evidence base has emerged, highlighting that community-based antiviral treatment provision is feasible and can result in clinical outcomes comparable to those achieved in specialty outpatient settings;Such provision can be in mainstream general practice, at community addiction centers, or in prisons; GPs must be well trained before offering such a service;Need for ongoing specialist supervision of PC practice;

Case 1

PA is a 64 year old man with history of HCV genotype 1a, PTSD, depression with prior suicide attempts, and IV opioid use disorder on suboxone but still intermittently using alcohol who presents for follow up with his PCP.

Evidence of cirrhosis on liver MRI, stage 4 fibrosis on biopsy with bridging, F4 fibrosis on FibroSure, AFP 20

ALT 49AST 64Alk P 79Tbili 0.4Dbili 0.1

HCV Genotype 1AHCV Viral Load 1,750,000INR 1.1Plt 230HAV Ab negative HAV IgM negative HBsAb non reactive HBsAg negativeHCV Ab reactive

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Lipoglycopeptide

Oxazolidinone

Dalbavancin pooled dataDISCOVER I, II

Boucher et al,NEJM 2014

Value Quality/Cost

Case 2

LN is a 32 year old woman with active opioid use disorder, is admitted to your hospital with a LUE abscess/cellulitis at the site of recent heroin injection. She uses her own works and does not share needles.

Started on Vanco empirically after surgery performs I+D. ID consultant recommends 7-10 day course of IV treatment What is appropriate disposition? IV access? Starting patient on opioid replacement therapyPatient wants to leave AMA

Culture data:Wound culture: MRSABlood culture: No growthVRE Rectal Swab: +Chem 7: Cr 1.4CBC: WNLLFT: WNLHCV: +HIV: -Tox: + opioids, benzos

Future DirectionsIntegration of Hepatitis C, primary care & SUD treatment;Long acting antibiotics vs shorter course for the treatment of SSTI in patients with & w/o SUD;New treatments for osteo & endocarditis;Linkage-to-care from inpatient to outpatient care;Your suggestions???

Learning pointsScope of Substance Use Disorder New treatments for Hepatitis C + barriersNew treatments for Skin and Skin Structure Infections (Cellulitis) + barriers2 Cases

AcknowledgementsThank you!Ana WeilJim MorrillUtibe Essien, Julian Mitton, Nathalee Kong

ReferencesAASLD/IDSA/IASUSA. HCV testing and linkage to care. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org/full-report/hcv-testing-and-linkage-care.

Afdhal, Nezam H. (2012). Fibroscan (Transient Elastrography) for the Measurement of Liver Fibrosis. Gastroenterology Hepatology, 8(9), 605-607.

Shaheen, A. M.M Wan A. F., & Myers R. P. (2007). FibroTest and FibroScan for the prediction of hepatitis C-related fibrosis: a systemetic review of diagnostic test accuracy. The American Journal of Gastroenterology, 102(11), 2589-2600.

Brew IF, Butt C, Wright N. Can antiviral treatment for hepatitis C be safely and effectively delivered in primary care?A narrative systematic review of the evidence base. Br J Gen Pract 2013

Arora S et al. Outcomes of Treatment for Hepatitis C Virus Infection by Primary Care Providers. NEJM 2011.

Huffman MM, Mousey AL, Hepatitis C for Primary Care Physicians. JABFM 2014.

Matruka A, et al. Expanding Primary Care Capacity to Treat Hepatitis C Virus Infection Through an Evidence-Based Care Model Arizona and Utah, 20122014. MMWR 2014.

Holmberg SD, Spradling PR, Moorman AC, Denniston MM. Hepatitis C in the United States. NEJM 2013.

Suryaprasad AG. Emerging Epidemic of Hepatitis C Virus Infections Among Young Nonurban Persons Who Inject Drugs in the United States, 20062012. CID 2014.

Chhatawal J. et al. Cost-Effectiveness and Budget Impact of Hepatitis C Virus Treatment With Sofosbovir and Ledipasvir in the United States. Annals of Internal Medicine. 2015.

Petta et al. Cost-Effectiveness of Sofosbuvir-Based Triple Therapy for Untreated Patients With Genotype 1 Chronic Hepatitis C. Hepatology. 2014.

Linas et al. The Cost-Effectiveness of Sufosbovir-Based Regimens for Treatment of Hepatitis C Virus Genotype 2 or 3 Infection. Annals of Internal Medicine. 2015.

Additional Slides

2015 PCORI RFAs $83M distributed to conduct pragmatic clinical trials & observational studies comparing alternatives for addressing prevention, diagnosis, treatment, mgmt of HCVPriority research question: interventions to support hard-to-treat patients with chronic HCV (e.g., SUD, medical comorbidities, mentally ill)Clinical Strategies for Managing and Reducing Long-Term Opioid Use for Chronic Pain

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