New Frontiers in Viral Hepatitis Patient Considerations with HIV/HCV Co-infection Lorren Sandt
The Past 250,000 306,000 Cure Treated No Cure People with HCV 4,000,000 2002 - 2008 Estimated Number of Previously Treated and CuredAssumptions•The cure rate over time is 45% (taking into account the higher re-treatment in the early years, thelarger number of G2/G3 in the early years and higher G1 naive today)Source: IMS Xponent Data (Retail TRx data)
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 ResistancePinK AALSD CME 2009
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 Cvirus 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. NEngl J Med. Mar 31 2011;364(13):1195-1206.
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 - 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
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; NEJM2004)
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 TotalDieterich D, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 46
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!
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
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 requiredSlide courtesy of Jurgen Hulskotte E et al., 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 771LBRockstroh. Beyond Phase 2: De Kanter C et al., 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 772LBTreating HIV/HCV Coinfected FDA Safety Announcement, dated 08 Feb 2012Patients Today. Abstract 72. 19th EMA press release, dated 17 Feb 2012CROI.. Seattle Washington. 2012 Merck "Dear Health Care Provider" letter, dated 06 Feb 2012
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 andhepatitis C virus (HCV). The investigators study liver disease progression in acohort 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 openHCV-1 and HIV-1 (INSIGHT)A Phase 3b Open Label Study of Telaprevir in Combination With Peginterferon for co-infection onAlfa-2a (Pegasys) and Ribavirin (Copegus) in Subjects Who Have Chronic HCV-1/HIV-1 Coinfection and Are Treatment-Naïve or Treatment-Experienced forHepatitis C www.clinicaltrials.govSafety and Efficacy Study of BMS-790052 Plus Peg-Interferon Alfa 2a and Ribavirinin 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 CoinfectedWith Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV)
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
Barriers to Adherence Telaprevir BoceprevirPEG/RBV LEAD-IN NO YESDOSE/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 MEALDURATION OF TX 12 WEEKS OF TPV 24-44 WEEKS OF BOC; 28-48 WEEKS OF PEG- 24-48 WEEKS OF PEG-IFN/RBV IFN/RBVCOST $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
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)
Potential Drug-Drug interactions are bountiful with the new HCV treatments.Discuss all medicationwith your provider. Illicit or Legal! www.hep-druginteractions.org
Mental HealthIn the US, most new HCV infections among IDUMental illness is prevalent among people with substanceuse 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.
Mental HealthIn 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 higherIn 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.
Lifestyle • obesity • diabetes • heart disease • joint problems and arthritis • high blood pressure • stroke
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 DepressionDunn et al. Am J Prev Med. 2005;28(1):1-8. Risk of other diseasesDunn 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 • 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 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
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.
Vaccination for Hepatitis A and Hepatitis B is recommended for people with liver disease.Post-Vaccination TestingPost-vaccination testing IS recommended for persons whosemedical management will depend on knowledge of theirimmune status.Post-vaccination testing should be completed 1-2 months afterthe third vaccine dose for results to be meaningful. Aprotective antibody response is 10 or more milliinternationalunits (>=10mIU/mL).Hepatitis B Vaccine: Fact SheetFrom U.S. Centers for Disease Control and Prevention
• 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
Thank You Lorren SandtLorren@HepCChallenge.org