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Hepatitis C: Cure and Control, Right Now

Hepatitis C: Cure and Control, Right Now. David L. Thomas Suresh Kumar Tomas Zabransky Dennis Leoutsakas . For persons living with HIV, hepatitis C is a major public health challenge that can and should be controlled. .

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Hepatitis C: Cure and Control, Right Now

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  1. Hepatitis C: Cure and Control, Right Now David L. Thomas Suresh Kumar Tomas Zabransky Dennis Leoutsakas

  2. For persons living with HIV, hepatitis C is a major public health challenge that can and should be controlled.

  3. For persons living with HIV, hepatitis C is a major public health challenge that can and should be controlled. For Persons Living With HIV: 1. HCV is common 2. HCV is clinically severe

  4. Adults and children living with HIV, 2008 Eastern Europe & Central Asia 1.5 million Western & Central Europe 850 000 North America 1.4 million East Asia 850 000 Middle East&North Africa 310 000 Caribbean 240 000 South & South-East Asia 3.8 million Sub-Saharan Africa 22.4 million Latin America 2.0 million Oceania 59 000 33.4 million

  5. HCV coinfection Occurs Commonly

  6. HCV coinfection Occurs in Most HIV-infected Injection Drug Users – West Abdala Intern J STD HIV 2003; Lincoln D HIV Med 2003; Rockstroh JID 2005; Thomas Medicine 1995

  7. HCV coinfection Occurs in Most HIV-infected Injection Drug Users - Asia Solomon SS JAIDS 2008; Mahanta AIDS Care 2009; Quan VM AIDS Care 2009; Liang HS J MicrobiolImmunol Infect 2008

  8. Hepatitis C is Common in HIV-infected IDUs Rockstroh JID 2005; Sulkowski Ann Intern Med 2003; Danta J AIDS 2007; Fierer J Infect Dis 2008

  9. HIV Infection Adversely Affects All Stages of Hepatitis C Infection Recovery Persistence

  10. HIV Infection Adversely Affects All Stages of Hepatitis C Infection HIV increases hepatitis C persistence, ALIVE cohort Recovery Persistence Odds of Persistence* CD4+/mm3

  11. HIV Infection Adversely Affects All Stages of Hepatitis C Infection HIV increases hepatitis C viral load, ALIVE cohort Recovery Persistence Viral load

  12. HIV Infection Adversely Affects All Stages of Hepatitis C HIV decreases response to HCV treatment (Peg 2a RBV 800 HCV 1) Infection Recovery Persistence Viral load Treatment response

  13. HIV Infection Adversely Affects All Stages of Hepatitis C Multi-center hemophilia cohort, 1192 HIV pos vs 624 HIV neg,1985-1998 Infection 10 Nonhepatic Deaths in HIV+ Recovery Persistence Viral load 8 Treatment 6 Hazard Rate per 100 PY Liver failure in HIV+ 4 Cirrhosis 2 Liver failure in HIV- 0 Liver failure or cancer 0 2 4 6 8 10 12 14 16 Years Since Enrollment

  14. HIV Infection Adversely Affects All Stages of Hepatitis C Multi-center hemophilia cohort, 1192 HIV pos vs 624 HIV neg,1985-1998 Infection 10 Nonhepatic Deaths in HIV+ Recovery Persistence Viral load 8 Treatment 6 Hazard Rate per 100 PY Liver failure in HIV+ 4 Cirrhosis 2 Liver failure in HIV- 0 Liver failure or cancer 0 2 4 6 8 10 12 14 16 Years Since Enrollment

  15. Antiretroviral Therapy is not Sufficient to Prevent the Adverse Effects of HIV • Antiretroviral therapy may slow fibrosis progression somewhat and may improve IFN sensitivity

  16. Antiretroviral Therapy is not Sufficient to Prevent the Adverse Effects of HIV • Antiretroviral therapy may slow fibrosis progression somewhat and may improve IFN sensitivity • Antiretroviral therapy is not sufficient to • Reduce the HCV RNA load2 • Restore treatment response3 • Prevent cirrhosis or liver failure4

  17. Survival for 3990 HIV coinfected Persons in Denmark by Years of HAART

  18. Markedly Lower Survival for HIV/HCV coinfected Persons in Denmark: 2000-2005

  19. Markedly Lower Survival for HIV/HCV coinfected Persons in Denmark: 2000-2005

  20. There is More to HIV/HCV Coinfection Than Statistics • Stigma • Neuropsychiatric effects • “Scar” of past IDU • Another “mountain to climb” • New “issues” and expensive medications • Injection flashbacks

  21. For persons living with HIV, hepatitis C is a major public health challenge that can and must be controlled.

  22. HCV Transmission Can be Prevented • Transfusion transmission has stopped where screening is done1 • Nosocomial spread reduced where bloodborne precautions observed2

  23. HCV Transmission Can be Prevented • Transfusion transmission has stopped where screening is done1 • Nosocomial spread reduced where bloodborne precautions observed2 • HCV incidence among IDUs has declined3 1Alter Nat Med 2000; 2Hutin Bull World Heath Organ; 3Amon Clin Infect Dis 2008; Mehta CROI 2010

  24. HCV Infection Can Be Controlled • Testing and counseling • Alcohol; HAV/HBV vaccination; secondary spread Institute of Medicine Report on Chronic Hepatitis, 2010

  25. HCV Infection Can Be Controlled • Testing and counseling • Alcohol; HAV/HBV vaccination; secondary spread • Treatment of chronic infection - cure • Sustained virologic response (SVR) possible1 • SVR: HCV not detected during and 6 mo after treatment 1Torriani NEJM 2004; 2Soriano Antivir Ther 2004

  26. HCV Infection Can Be Cured • Testing and counseling • Treatment of chronic infection • Sustained virologic response is possible1 • Sustained virologic response is durable2 • No recurrence in 77 HIV/HCV coinfected persons followed 4466 months post SVR 1Torriani NEJM 2004; 2Soriano Antivir Ther 2004

  27. HCV Infection Can Be Cured Survival after HCV treatment for 493 with no SVR and 218 with SVR • Testing and counseling • Treatment of chronic infection • Sustained virologic response is possible1 • Sustained virologic response is durable2 • Sustained virologic response prevents death3 Months after HCV treatment 1Torriani NEJM 2004; 2Soriano AntivirTher 2004; 3Berenguer Hepatology 2009

  28. Higher HCV Cure Rates Will Come HCV Protease Inhibitor (Telaprevir) Improves SVR and May Reduce Treatment Duration Standard of care for 24 wks along with PI for first 12 wks Standard of care for 48 wks McHutchisonN Engl J Med 2009

  29. “Highly Active anti-HCV Therapy” 84 Phase 1-3 Anti-HCV Studies Are Underway www.clinicaltrials.gov

  30. HCV Control is Possible. But, How? For Whom?

  31. HCV Prevention is Possible, but Not Happening Right Now • Prevention • Harm reduction can work but needs to be intensified and expanded Mehta S, CROI 2010

  32. HCV Control is Possible, but Not Happening Right Now HIV/HCV coinfected patients attending the Johns Hopkins HIV clinic 1999-2003 Mehta SH et al, AIDS, 2006

  33. HCV Control is Possible, but Not Happening Right Now • Treatment • SVR is possible but few HIV/HCV coinfected persons are cured • Most HCV infected persons worldwide have no access to testing • 70% unaware in USA2 1Mehta SH , AIDS, 2006; Grebeley J Viral Hep 2009; 2IOM Report on Chronic Hepatitis, 2010

  34. HCV Control is Possible, but Not Happening Right Now • Treatment • SVR is possible but few HIV/HCV coinfected persons are cured1 • Most HCV infected persons worldwide have no access to testing • 70% unaware in USA2 • Treatment/testing costs are prohibitive 1Mehta SH , AIDS, 2006; Grebeley J Viral Hep 2009; 2IOM Report on Chronic Hepatitis, 2010

  35. Global Public Health Impact of HCV Control Requires a Radically New Approach Percent SVR 1991 1998 2001 2007 2018

  36. Global Public Health Impact of HCV Control Requires a Radically New Approach Possible to Cure HCV Infection Percent SVR (individual) 2018

  37. Global Public Health Impact of HCV Control Requires a Radically New Approach Possible to Cure HCV Infection <10% 0f 170 mil with HCV Percent SVR (individual) 2018

  38. Global Public Health Impact of HCV Control Requires a Radically New Approach Possible to Cure HCV Infection Global impact of new treatments is negligible unless expanded uptake worldwide Percent SVR (individual) Percent SVR (population) 2018 2018

  39. For persons living with HIV, hepatitis C is a major public health challenge that can and should be controlled. • Harm reduction intensified • Testing expanded • Treatment possible

  40. Like HIV, HCV Treatment Will Need to Be Expanded to Impact Global Health "Let's rejoice in the fact that today we have treatments that work ... what we need is the political will to go the extra mile to deliver universal access.“ J Montaner

  41. Acknowledgements • Coauthors: Thomas Zabransky, Suresh Kumar, Dennis Leoutsakas • Slides: Tom Quinn and Shruti Mehta • JHU HIV Clinic: Richard Moore and Mark Sulkowski • ALIVE Cohort: David Vlahov, Stephanie Strathdee, Kenrad Nelson, Richard Garfein, Greg Kirk • Funding: NIH, NIDA

  42. Biologic, Historic, and Sociologic Basis for HCV Coinfection Rates • HCV is ten fold more transmissible from single needle stick1 • HCV infections spread worldwide before HIV2 • Older IDUs teach new initiates by ‘sharing’3

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