new frontiers sandt
TRANSCRIPT
New Frontiers in Viral Hepatitis
Patient Considerations with HIV/HCV Co-infection
Lorren Sandt
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)
250,000 306,000
4,000,000
CureTreated No CurePeople with HCV
The Past
Making A Treatment Decision:A Constellation of Considerations
Duration ofinfection
Personal plans(marriage,
pregnancy)Age
ALT
HIV coinfection
ExtrahepaticFeatures
(Fatigue, EMC, PCT)
Patient"mindset"
Genotype virusGenotype Patient (IL28)
Contraindications& comorbidities
Insulin Resistance
Histologic stage20%+ life time risk
Of cirrhosis
Family and othersupport
Occupation
PinK AALSD CME 2009
The New HCV Treatment
PEG-IFN& RBV:
44%
With boceprevir:
63%
With telaprevir:
75%
Overall Triple Therapy Cure Rates Genotype 1, Treatment Naïve
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.
% SVR, overall
The New HCV Treatment
Overall Triple Therapy Cure Rates
Genotype 1 Treatment Experienced with Bridging Fibrosis/Cirrhosis
telaprevir boceprevirZeuzem 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
HCV: “Drug” Targets
NS5a inhibitors
• 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
HCV - a Rapidly Changing Landscape
HCV-796 (Polymerase)
ISIS 14803 (Antisense)
BILN 2061 (Protease)
Heptazyme (Ribozyme)
NM-283 (Polymerase)
ACH-806/GS-9132 (NS4a)
ANA975(TLR agonist)
UT-231B(Imino sugar)
VX-497(IMPDH inhibitor)
JTK-003(Polymerase)
CPG 10101(TLR agonist)
R803(Polymerase)
R7025(Interferon-alpha )
Courtesy of Nelson D.
R1626(polymerase)
Viramidine (RBV analogue)
Idenix compounds2010
HCV - a Rapidly Changing Landscape
Current SOC in Co-infection
Data from clinical trials; 24- 48 weeks of PEG-IFN + RBV (by genotype and HIV status)
SVR overall SVR, genotype 1
SVR, genotype 2 & 3
HIV/HCV coinfected
27% to 44% 14% to 38% 53% to 73%
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)
71
33
69
50
80
50
74
45
0
10
20
30
40
50
60
70
80
90
100
Pa
tie
nts
wit
h U
nd
ete
cta
ble
HC
V R
NA
(%
)
No ART EFV/TDF/FTC ATV/r/TDF/FTC Total
n/N = 5/7 11/16 12/15 28/38
T/PR PR2/6 4/8 4/8 10/22
Study 110: SVR Rates 12 Weeks Post-Treatment (SVR12)
Dieterich D, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 46
*Patient was defined as SVR12 if HCV RNA was < LLOQ in the visit window
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!
The Coming SOC in Co-infection?
New DAA’s - Caution
Telaprevir: DDIs with HIV Antiretrovirals
HIV antiretroviral Recommendation
Studies completed
Atazanavir/r Clinical and laboratory monitoring for hyperbilirubinaemia is recommended
Darunavir/rFosamprenavir/rLopinavir/r
Not recommended
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
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/rFosamprenavir/rLopinavir/r
Not recommended
Efavirenz Not recommended
Raltegravir No dose adjustment required
Slide courtesy of Jurgen Rockstroh. Beyond Phase 2: Treating HIV/HCV Coinfected Patients Today. Abstract 72. 19th CROI.. Seattle Washington. 2012
Hulskotte E et al., 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 771LBDe Kanter C et al., 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 772LB
FDA Safety Announcement, dated 08 Feb 2012 EMA press release, dated 17 Feb 2012
Merck "Dear Health Care Provider" letter, dated 06 Feb 2012
Many Opportunities for Care
HCV/HIV Coinfection: Antiviral Therapy and Fibrosis – 15 year studyThe 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 HCV-1 and HIV-1 (INSIGHT)A Phase 3b Open Label Study of Telaprevir in Combination With Peginterferon 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
Safety and Efficacy Study of BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirin in Untreated Hepatitis C Patients Coinfected With HIV VirusA 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)
244 studies with 91 open for co-infection on
www.clinicaltrials.gov
Do Your Homework
www.treatmentactiongroup.org
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
Drug Levels, Resistance & Adherence
Barriers to Adherence
Telaprevir Boceprevir
PEG/RBV LEAD-IN NO YES
DOSE/PILL BURDEN 800 MG/ Q 7-9 HRS, 8 PILLSWITH HIGH FAT MEAL
750 MG/ Q 7-9 HRS, 12 PILLSWITH SNACK OR MEAL
DURATION OF TX 12 WEEKS OF TPV24-48 WEEKS OF PEG-IFN/RBV
24-44 WEEKS OF BOC; 28-48 WEEKS OF PEG-IFN/RBV
COST $4125/WEEK (TOTAL OF $49,500)
$1100 WEEK (TOTAL: $ 26,400 TO $48,400)
SIDE EFFECTS RASH, ANEMIA, GASTROINTESTINAL DISTRESS, ANAL/RECTAL ITCHING & BURNING
ANEMIA, NEUTROPENIA, THROMBOCYTOPENIA, DYSGEUSIA
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)
HCV Therapy – the bottom line
Ongoing drug use– illicit and legal
Potential Drug-Drug interactions are
bountiful with the new HCV treatments.
Discuss all medication with your provider. Illicit
or Legal!www.hep-druginteractions.org
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
Mental Health
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.
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) HCVprevalence 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.
Mental Health
Detrimental Effects of Inactivity on Humans
• obesity• diabetes• heart disease• joint problems and arthritis• high blood pressure• stroke
Lifestyle
Metabolic rate
Efficiency of blood sugar use
Immune Function
Potential response rate to IFN-based therapy
Energy
Mood
Quality of life
Insulin resistance
Liver enzymes
Risk of fatty liver
Risk of blood sugar abnormalities
Risk of abnormal fat deposits in the blood vessels
Depression
Risk of other diseases
Exercising for a Healthy Body Weight
Dunn et al. Am J Prev Med. 2005;28(1):1-8.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.
Lifestyle
Exercising for a Healthy Mind
• 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.
Lifestyle
Take Your Pick!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, gardening4 hours horseback riding, water aerobics, washing the car,
washing windows, house cleaning4 ½ hours swing dancing, ping pong, golfing6 hours casual walking, playing piano7 hours vacuuming16 ½ hours kissing
Lifestyle
• 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.
Keep Your Body Moving
Lifestyle
Vaccination for HAV and HBV
Vaccination for Hepatitis A and Hepatitis B is recommended for people with liver disease.
Post-Vaccination TestingPost-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 SheetFrom U.S. Centers for Disease Control and Prevention
Advocacy
• 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
