1. New Frontiers in Viral Hepatitis
Patient Considerations with
HIV/HCV Co-infection
Lorren Sandt

2. The Past
250,000
306,000
Cure
Treated No Cure
People with HCV
4,000,000
2002 - 2008 Estimated Number of
Previously Treated and Cured
Assumptions
•The cure rate over time is 45% (taking into account the higher re-treatment in the early years, the
larger number of G2/G3 in the early years and higher G1 naive today)
Source: IMS Xponent Data (Retail TRx data)

3. Making A Treatment Decision:
A Constellation of Considerations
Histologic stage
Genotype virus Duration of
20%+ life time risk
Genotype Patient (IL28) infection
Of cirrhosis
Personal plans
Family and other
(marriage, Age
support
pregnancy)
Patient
ALT Occupation
"mindset"
Extrahepatic Contraindications
Features HIV coinfection & comorbidities
(Fatigue, EMC, PCT) Insulin Resistance
PinK AALSD CME 2009

4. The New HCV Treatment
Overall Triple Therapy Cure Rates
Genotype 1, Treatment Naïve
PEG-IFN With With
% SVR, overall & RBV: boceprevir: telaprevir:
44% 63% 75%
Jacobson IM, McHutchison JG, Dusheiko G, et al. Telaprevir for previously untreated chronic hepatitis C
virus infection. N Engl J Med. Jun 23 2011;364(25):2405-2416.
Poordad F, McCone J, Jr., Bacon BR, et al. Boceprevir for untreated chronic HCV genotype 1 infection. N
Engl J Med. Mar 31 2011;364(13):1195-1206.

5. The New HCV Treatment
Overall
Triple Therapy Cure Rates
Genotype 1
Treatment Experienced with
Bridging Fibrosis/Cirrhosis
telaprevir boceprevir
Zeuzem S. et al. REALIZE final results. J Hepatology 2011;54:S3.
Bacon BR, et al. RESPOND-2 final results. N Engl J Med 2011;364:1207-1217

6. HCV: “Drug” Targets
NS5a inhibitors

7. HCV - a Rapidly Changing Landscape
• Clinical trials are exploring interferon-free and
ribavirin-free regimens
• Clinical trials are looking at “quad” – two DAAs with
different mechanisms of action, with peginterferon
and ribavirin
• Host targeting agents
• New types and formulations of interferon

8. HCV - a Rapidly Changing Landscape
BILN 2061
ISIS 14803
(Protease)
(Antisense)
JTK-003
UT-231B (Polymerase)
(Imino sugar)
Heptazyme
(Ribozyme) HCV-796
(Polymerase)
VX-497
NM-283
(IMPDH inhibitor)
(Polymerase)
Viramidine
(RBV analogue)
R803
(Polymerase)
Idenix compounds
2010
R1626
ANA975 ACH-806/GS-9132 R7025 (polymerase)
CPG 10101
(TLR agonist) (NS4a) (Interferon-alpha )
(TLR agonist)
Courtesy of Nelson D.

9. Data from clinical trials; 24- 48 weeks of
PEG-IFN + RBV (by genotype and HIV status)
SVR overall SVR, SVR, genotype
genotype 1 2&3
HIV/HCV 27% to 44% 14% to 38% 53% to 73%
coinfected
HCV mono 56% to 61% 42% to 44% 70% to 82%
(Carrat et al; JAMA 2004; Chung et al: NEJM 2004; Fried et al; NEJM 2002;
Manns et al; Lancet 2001; Laguno et al; AIDS 2004; Torriani et al; NEJM
2004)

10. The Coming SOC in Co-infection?
Patients with Undetectable HCV RNA (%)
Study 110: SVR Rates
100 12 Weeks Post-Treatment (SVR12)
90 80
80 74 *Patient was defined as SVR12 if HCV RNA was < LLOQ in the visit
71 69 window
70
60
50 50 45
50
40 33
30
20
10
0
n/N = 5/7 11/16 12/15 28/38 2/6 4/8 4/8 10/22
T/PR PR
No ART EFV/TDF/FTC ATV/r/TDF/FTC Total
Dieterich D, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 46

11. The Coming SOC in Co-infection?
• HIV/HCV Co-infection Studies are not complete.
• This is not yet FDA approved therapy for co-
infected individuals
• Easy to treat population studied first
• Results may not be the same in clinical
practice
• CAUTION!
• Not all Drug-drug interaction studies are
complete!

13. Telaprevir: DDIs with HIV Antiretrovirals
HIV antiretroviral Recommendation
Studies completed
Atazanavir/r Clinical and laboratory monitoring for
hyperbilirubinaemia is recommended
Darunavir/r
Fosamprenavir/r Not recommended
Lopinavir/r
Efavirenz TVR dose increase necessary (1125 mg q8h)
Raltegravir No dose adjustment required
Tenofovir Increased clinical and laboratory monitoring is
warranted
Slide courtesy of Jurgen Rockstroh. Beyond Phase 2:
Treating HIV/HCV Coinfected Patients Today. Abstract 72. 19th CROI.. Seattle
Washington. 2012

14. Boceprevir: DDIs with HIV Antiretrovirals
HIV antiretroviral Recommendation
Studies completed
Atazanavir/r In general not recommended; EMEA says can be
considered on a case-by-case basis if patient has no
prior HIV drug resistance and is suppressed
Darunavir/r
Fosamprenavir/r Not recommended
Lopinavir/r
Efavirenz Not recommended
Raltegravir No dose adjustment required
Slide courtesy of Jurgen Hulskotte E et al., 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 771LB
Rockstroh. Beyond Phase 2: De Kanter C et al., 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 772LB
Treating HIV/HCV Coinfected FDA Safety Announcement, dated 08 Feb 2012
Patients Today. Abstract 72. 19th EMA press release, dated 17 Feb 2012
CROI.. Seattle Washington. 2012 Merck "Dear Health Care Provider" letter, dated 06 Feb 2012

15. HCV/HIV Coinfection: Antiviral Therapy and Fibrosis – 15 year study
The chief purpose of this research is to understand how antiretroviral therapy
(ART) affects progression of liver disease in persons co-infected with HIV and
hepatitis C virus (HCV). The investigators study liver disease progression in a
cohort of dually infected persons according to the success of ART.
An Efficacy and Safety Study of Telaprevir in Patients Infected With Both Chronic
244 studies with 91 open
HCV-1 and HIV-1 (INSIGHT)
A Phase 3b Open Label Study of Telaprevir in Combination With Peginterferon
for co-infection on
Alfa-2a (Pegasys) and Ribavirin (Copegus) in Subjects Who Have Chronic HCV-
1/HIV-1 Coinfection and Are Treatment-Naïve or Treatment-Experienced for
Hepatitis C www.clinicaltrials.gov
Safety and Efficacy Study of BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirin
in Untreated Hepatitis C Patients Coinfected With HIV Virus
A Phase 3, Open Label Study of Safety and Efficacy With BMS-790052 Plus Peg-
Interferon Alfa 2a and Ribavirin in Previously Untreated HCV Patients Coinfected
With Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)

16. www.treatmentactiongroup.org

17. Why Doesn’t Treatment Work?
• When interferon doesn’t work—some people
have a virus that is not responsive to interferon
• When people cannot tolerate treatment, and stop
it
• When people are taking other medications that
may clash with a protease inhibitor (drug-drug
interaction)
• When people miss doses of their protease
inhibitor and/or peginterferon and ribavirin, and
drug resistance emerges

18. Drug Levels, Resistance & Adherence

19. Barriers to Adherence
Telaprevir Boceprevir
PEG/RBV LEAD-IN NO YES
DOSE/PILL BURDEN 800 MG/ Q 7-9 HRS, 8 PILLS 750 MG/ Q 7-9 HRS, 12 PILLS
WITH HIGH FAT MEAL WITH SNACK OR MEAL
DURATION OF TX 12 WEEKS OF TPV 24-44 WEEKS OF BOC; 28-48 WEEKS OF PEG-
24-48 WEEKS OF PEG-IFN/RBV IFN/RBV
COST $4125/WEEK (TOTAL OF $1100 WEEK (TOTAL: $ 26,400 TO $48,400)
$49,500)
SIDE EFFECTS RASH, ANEMIA, ANEMIA, NEUTROPENIA,
GASTROINTESTINAL THROMBOCYTOPENIA, DYSGEUSIA
DISTRESS, ANAL/RECTAL
ITCHING & BURNING

20. HCV Therapy – the bottom line
Adherence is critical!
Successful HCV treatment must
rapidly—and fully—suppress
hepatitis C virus, & keep it
completely suppressed throughout
the course of treatment (12-72
weeks)

21. Potential Drug-Drug
interactions are
bountiful with the new
HCV treatments.
Discuss all medication
with your provider. Illicit
or Legal!
www.hep-druginteractions.org

22. Mental Health
In the US, most new HCV infections among IDU
Mental illness is prevalent among people with substance
use disorders (SUDs) and vice versa:
 50% of people with serious mental illness have SUDs
 53% of people with SUDs have co-occurring mental
illness
 People with psychiatric disorders are almost 3 times
more likely to have a SUD than the general population
Regier et al; Comorbidity of mental disorders with alcohol and other drug abuse.
Results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990.
Rosenberg et al. Hepatitis C virus and HIV co-infection in people with severe
mental illness and substance use disorders.AIDS 2005.

23. Mental Health
In a sample of 931 people with serious mental illnesses
(SMI)
HCV prevalence was 19.6% (versus 1.6% among the
general population)---more than 11 times higher
In a sample of veterans (with and without SMIs) HCV
prevalence was:
• 8.1% among people with bipolar disorder
• 7.1% of people with schizophrenia
• 2.5% of people without an SMI
Armstrong et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002.
Ann Intern Med 2006.
Himelhoch, et al. Understanding associations between serious mental illness and hepatitis C virus
among veterans: a national multivariate analysis. Psychosomatics. 2009 Jan-Feb;50(1):30-7.
Rosenberg, et al. The five-site health and risk study of blood-borne infections among persons with
severe mental illness. Psychiatr Serv. 2003 Jun;54(6):827-35.

24. Lifestyle
• obesity
• diabetes
• heart disease
• joint problems and arthritis
• high blood pressure
• stroke

25. Lifestyle
Exercising for a Healthy Body Weight
Metabolic rate Insulin resistance
Efficiency of blood sugar use Liver enzymes
Immune Function Risk of fatty liver
Potential response rate to Risk of blood sugar
IFN-based therapy abnormalities
Energy Risk of abnormal fat
Mood deposits in the blood
vessels
Quality of life
Depression
Dunn et al. Am J Prev Med. 2005;28(1):1-8. Risk of other diseases
Dunn et al. Control Clin Trials. 2002;23(5):584-603.
Singh et al. J Gerontol A Biol Sci Med Sci. 2005;60(6):768-76.
Fairey AS et al. J Appl Physiol. 2005;98(4):1534-40.
Kohut ML et al. Exerc Immunol Rev. 2004;10:6-41.
Hong S et al. J Appl Physiol. 2005;98(3):1057-63.
Smith TP et al. J Appl Physiol. 2004;97(2):491-8.

26. Lifestyle
• Exercise can be measured by the number of
calories burned.
• A recent study found the optimal benefit on
depression occurs when 17.5 calories per
kilogram of body weight is expended per
week.
What does that mean for you and me?
Dunn et al. Am J Prev Med. 2005;28(1):1-8.

27. Lifestyle
2 hours handball, jogging, rock climbing, jumping rope, touch
football, tennis, swimming, stair-climbing, cross-
country skiing
2 ½ hours bicycling, weight-lifting, soccer, roller blading,
racquetball, karate
3 hours aerobics, hiking, half-court basketball, canoeing,
kayaking, working out at the gym, water skiing, brisk
walking, stacking fire wood, downhill skiing, shoveling
snow, scrubbing floors, rearranging furniture, ice skating
3 ½ hours yoga, whitewater rafting, raking, planting flowers,
mowing the lawn
3 ¾ hours ballroom dancing, gardening
4 hours horseback riding, water aerobics, washing the car,
washing windows, house cleaning
4 ½ hours swing dancing, ping pong, golfing
6 hours casual walking, playing piano
7 hours vacuuming
16 ½ hours kissing

28. Lifestyle
Keep Your Body Moving
• for your mental health
• for your immune health
• for your well-being and peace of mind
• for your heart and lungs
• for your muscles and bones …
For your life.

29. Vaccination for Hepatitis A and Hepatitis B is
recommended for people with liver disease.
Post-Vaccination Testing
Post-vaccination testing IS recommended for persons whose
medical management will depend on knowledge of their
immune status.
Post-vaccination testing should be completed 1-2 months after
the third vaccine dose for results to be meaningful. A
protective antibody response is 10 or more milliinternational
units (>=10mIU/mL).
Hepatitis B Vaccine: Fact Sheet
From U.S. Centers for Disease Control and Prevention

30. • Participate in Health Reform implementation at
the state and local level
• Institutionalize and Implement the new Birth
cohort screening guidelines for HCV
• Coordinate care for your patients – Be a part of
a team
• Provide information and assistance to patients
to access Patient Assistance Programs

31. Thank You
Lorren Sandt
Lorren@HepCChallenge.org