Invited talk given at DHMC in November 2015

1. New treatments for the infectious
complications of substance use disorders,
and barriers to implementation.
Benjamin Bearnot
November 10, 2015

2. Disclosures
• No conflicts to report

3. Outline
• Scope of Substance Use Disorder
• New treatments for Hepatitis C + barriers
• New treatments for Skin and Skin Structure
Infections (Cellulitis) + barriers
• 2 Cases

4. Scope of the Problem
Case and Deaton,
PNAS 2015
All-cause mortality, ages 45–54 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).

5. Scope of the Problem
Case and Deaton,
PNAS 2015

6. Opioids of Misuse
Cicero et al,
NEJM 2015

7. HCV Epidemiology
* Includes cases contracted in
the hospital or during childbirth
Source: Centers for Disease
Control and Prevention
Sexual
17%
Unknown
10%
Past transfusion 3%
Occupational 4%
Other 9%*
Injection drug
use 57%
Holmberg et al,
NEJM 2013

8. HCV Epidemiology Cont.
Suryaprasad, CID 2014

9. Genotype
1
Options
Duration SVR for
tx naïve
pts
SVR for tx
experienced
or cirrhotic
pts
Cost Side
Effects
Harvoni
(Sofosbuvir /
Ledipasvir)
• 8 wks (no cirrhosis,
low VL)
• 12 wks (high VL)
• 24 wks (cirrhosis)
98-99% 97% (24 wks) $94,500 Fatigue (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) $83,319 Fatigue (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).

10. Genotype
2
Options
Duration SVR for
tx naïve
pts
SVR for tx
experienced
or cirrhotic
pts
Cost Side
Effects
Sofosbuvir /
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% $63,000 Fatigue (14%)
Headache (14%)
Nausea (8%)
Diarrhea (5%)

11. Genotype
3
Options
Duration SVR for tx
naïve pts
SVR for tx
experienced
or cirrhotic
pts
Cost Side Effects
Sofosbuvir /
Ribavirin /
Peginterferon
12 wks 97% 87% $94,000 Fatigue (59%)
Headache (36%)
Nausea (34%)
Insomnia (25%)
Anemia (21%)
Anorexia (18%)
Neutropenia (17%)
Flu-like sx (16%)
Irritability (13%)
Sofosbuvir /
Ribavirin
24 wks 93% • 77% (tx
experienced)
• 92% (cirrhosis,
tx naïve)
$169,000 Fatigue (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%)

12. HCV Treatment in Primary Care Setting
MMWR 2014 update, ongoing implementation, with ~30% on tx with DAAs
Arora , NEJM 2011

13. HCV Treatment in Primary Care Setting
• Systematic review in British Journal of General Practice,
December 2013
– 12 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;

14. 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 49
AST 64
Alk P 79
Tbili 0.4
Dbili 0.1
HCV Genotype – 1A
HCV Viral Load – 1,750,000
INR 1.1
Plt 230
HAV Ab – negative
HAV IgM – negative
HBsAb – non reactive
HBsAg – negative
HCV Ab – reactive

19. Lipoglycopeptide Oxazolidinone

20. Dalbavancin pooled data
DISCOVER I, II
Boucher et al,
NEJM 2014

21. Value ≈ Quality/Cost

22. 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 therapy
• Patient wants to leave AMA
Culture data:
Wound culture: MRSA
Blood culture: No growth
VRE Rectal Swab: +
Chem 7: Cr 1.4
CBC: WNL
LFT: WNL
HCV: +
HIV: -
Tox: + opioids, benzos

23. Future Directions
• Integration 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???

24. Learning points
• Scope of Substance Use Disorder
• New treatments for Hepatitis C + barriers
• New treatments for Skin and Skin Structure
Infections (Cellulitis) + barriers
• 2 Cases

25. Acknowledgements
• Thank you!
• Ana Weil
• Jim Morrill
• Utibe Essien, Julian Mitton, Nathalee Kong

26. References
AASLD/IDSA/IAS–USA. 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, 2012–2014. 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,
2006–2012. 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.

27. Additional Slides

28. 2015 PCORI RFAs
1. $83M distributed to conduct pragmatic
clinical trials & observational studies
comparing alternatives for addressing
prevention, diagnosis, treatment, mgmt of
HCV
– Priority research question: interventions to
support hard-to-treat patients with chronic HCV
(e.g., SUD, medical comorbidities, mentally ill)
2. Clinical Strategies for Managing and Reducing
Long-Term Opioid Use for Chronic Pain