There are three types of people People who don t learn from their mistakes People who do learn from their mistakes People who learn from the mistakes of others
Treat Now
Summary of EASL 2014 100% 100 90 80 SVR24 rate (%) 70 60 50 40 30 20 10 0
SVR 4 after treatment with PR + Simeprevir, Faldaprevir and Sofosbuvir + R + P for hepatitis C naïve pts.: Comparison beteween data in HIV + vs HIV- 78/124 87/11 4 88/145 28/42 295/327 17/19 IN THE DAA ERA HIV+ WILL NOT BE A SPECIAL POPULATION WITH AN UNMET NEED 414/570 169/239 419/521 42/53 Gane EJ EASL 2013 ; Jacobson IM NEJM 2013; Lawitz E et al NEJM 2013; Ferenci F et al EASL 2012 Manns MP et al EASL 2012 Jacobson EASL 2012 Rodriguez Torres M et al IDSA 2013; Dieterich EACS 2013; Rockstroh The Liver Congress 2013
Study Design Fifty HIV/HCV genotype 1, treatment-naive subjects HAI fibrosis stage 0 3 Wk 0 Wk 12 48 week follow up ARV Untreated (n=13) CD4 count stable + HIV RNA <500 copies OR - CD4 count > 500 cells/mm 3 SVR 12 SOF/LDV (400/90mg) ARV Treated (n=37) - CD4 count > 100 cells/mm 3 - HIV RNA < 40 copies - Current ARVs 8 weeks ARVs: tenofovir, emtricitabine, efavirenz, rilpivirine and raltegravir SVR 4 Interim results
Treatment Response (Observed) 100 0 ARV - 13/ 13 13/13 13/ 13 12/12 10/10 10/10 ARV + 37/37 37/37 30/30 22/22
Why do you not want to have hepatitis C and HIV
Why do you not want to have hepatitis C and HIV Transmission
Acute HCV among HIV+ MSM Canada 23 : ~30 cases Prevalence chronic HCV/HIV 24 19%: 11.200 USA 1,2 : 55 cases Prevalence chronic HCV/HIV 12-14 15 30%: 180.000 360.000 Lebanon 22 : 1 case Prevalence chronic HCV/HIV 25 49%: 1.500 Europe: 1068 cases Prevalence chronic HCV/HIV 14,15 25%: 185.500 -UK 3,4 552 -Germany 5,18, 27 157 -France 6,7 126 -Netherlands 8,17 97 -Belgium 20 69 -Swiss 9 23 -Italy 10 21 -Denmark 21 13 -Spain 26 ~8 Australia 11 : 47 cases Prevalence chronic HCV/HIV 16,19 < 1%: 1.000 Taiwan 28 : 28 cases Prevalence chronic HCV/HIV 29 55%: 8.800 1:Luetkemeyer JAIDS 2006; 2:Cox Gastroenterology 2008; 3:Giraudon Sex Transm Infect 2008; 4:Ruf Eurosurveill 2008; 5:Vogel CID 2009; 6:Gambotti Euro Surveill 2005; 7:Morin Eur J Gastro Hepat 2011; 8:Urbanus AIDS 2009; 9:Rauch CID 2005; 10:Gallotta 4th Works. HIV & Hep. Coinf. 2008; 11:Matthews CID 2009; 12:Sherman CID 2002; 13:Backus JAIDS 2005; 14:UNAIDS Report 2008; 15:Soriano JID 2008; 16:Matthews CID 2011; 17:Arends Neth J Med 2011; 18:Neukam HIV Med 2011; 19:Pfafferott PLoS One 2011; 20:Bottieau Euro Surveill 2010; 21:Barfod Scand JID 2011; 22:Dionne-Odom Lancet Infect Dis 2009; 23:Hull personal conversation 2011; 24:Remis Public Health Agency of Canada 2002; 25:UNGASS Country progress Report 2010; 26:Soriano personal conversation 2011; 27:Boesecke 18 th CROI Boston 2011 abstract #113; 28:Sun Liver International 2011; 29:Lee J F Med Assoc 2008
Seminal Positivity for HCV P=0.033 % 40 35 30 25 20 15 10 5 0 HCV HCV/HIV % Semen +ve Briat AIDS 2005
Why do you not want to have hepatitis C and HIV Transmission Stigma
Why do you not want to have hepatitis C and HIV Transmission Stigma More Rapid Progression of disease
No Association of Hepatitis C with AIDS Defining Events Hung et al [11] Klein et al [19] Rockstroh et al [54] Stebbing et al [59] Sulkowski et al [55] Sullivan et al [56] Tedaldi et al [57] Combined.25.5 11.12 3 6 9 Risk Ratio
Increased Risk of Cirrhosis and ESLD Due to HIV/HCV Coinfection Histologic Cirrhosis Relative Risk Decompensated Liver Disease Relative Risk Makris (UK) Soto (Spain) Pol (France) Benhamou (France) Combined Eyster (USA) Telfer (UK) Makris (UK) Lesens (Canada) Combined.76 1.0 2.07 10.83 HCV Only HIV/HCV.61 1.0 6.14 10 HCV Only HIV/HCV Graham CS, et al. CID. 2001;33:562-569.
Why do you not want to have hepatitis C and HIV Transmission Stigma More Rapid Progression of disease Increase in now known HIV related comorbidities
HIV/HCV co-infection may result in Global cognitive impairment Cognitive-motor impairment Dementia Peripheral neuropathy multi-systemic disorders Neurologic disease Cerebrovascular disease Acute myocardial infarction Opportunistic infections Wasting syndrome Proteinuria Acute renal failure Chronic kidney disease Cardiovascular HIV disease progression Kidney disease Immune activation HIV/HCV Immune dysregulation Metabolic disorders Liver disease GI tract Diabetes mellitus Insulin resistance Steatosis Fibrosis Cirrhosis End-stage liver disease Liver-related death Microbial translocation Osteonecrosis Osteoporosis Bone fracture Bone disorders CD4 apoptosis Abnormal T-cell responses and cytokine production Cytotoxic T-cell accumulation in liver CD4 recovery post-haart Severe immunodeficiency GI: gastrointestinal; HAART: highly active antiretroviral therapy Operskalski EA & Kovacs A. Curr HIV/AIDS Rep 2011;8:12 22
DIABETES
Why do you not want to have hepatitis C and HIV Transmission Stigma More Rapid Progression of disease Increase in now known HIV related comorbidities Increase in HAART toxicity
Incidence of Grade 2 or Above Liver Enzyme Elevation 35 30 25 % 20 15 10 5 Hep C-ve Hep C+ve 0 NRTI NNRTI PI BPI Mixed Benhamou Y, et al. 13th CROI 2006. Abstract 88.
Why do you not want to have hepatitis C and HIV Transmission Stigma More Rapid Progression of disease Increase in now known HIV related comorbidities Increase in HAART toxicity People die
Changing Patterns of the Causes of Death in a Swiss Cohort (SHCS) SHCS is a prospective observational cohort Characteristics of participants that died from 2005-2009 459 deaths/9,053 participants (5.1%) Causes of Death in Participants in the Swiss HIV Cohort Study in 3 different Time Periods, and in the Swiss Population in 2007 Proportion 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 1984-1995 1996-2004 2005-2009 Swiss 2007 AIDS Non-AIDS malignancy Non-AIDS infection Liver Heart CNS Kidney Intestine/pancreas Lung Suicide Substance use Accident/homicide Other UnKnown Years of Death of HIV+ Persons Versus Swiss Population Ruppik M, et al. 18th CROI; Boston, MA; February 27-March 2, 2011. Abst. 789.
Causes of Death among People with Hepatitis C in NYC, 2000-2011 Jessie Pinchoff, PhD Candidate, MPH, Ann Drobnik, MPH, Jennifer Fuld, PhD Candidate, MA, Katherine Bornschlegel, Sarah L. Braunstein PhD, Jay K. Varma, MD Division of Disease Control, New York City Department of Health and Mental Hygiene (NYC DOHMH) IDSA 2013
Male circumcision 1-3 Treatment of STIs 4 HIV prevention Behavioural intervention HIV counselling and testing 5 Female condoms Male condoms Microbicides for women 13 Oral pre-exposure prophylaxis 9-12 MSM, couples, heterosexuals, IDUs Post Exposure prophylaxis (PEP) 8 Note: PMTCT, screening transfusions, harm reduction, universal precautions, etc have not been included. This is focused on reducing sexual transmission. 1. Auvert et al. PLoS Med 2005;2:e298. 2. Gray et al. Lancet 2007;369:657-66. 3. Bailey et al. Lancet 2007;369:643-56. 4. Grosskurth et al. Lancet 2000;355:1981-7. 5. Sweat et al. Lancet. 2000;356:113-21. 6. Donnell et al. Lancet 2010;375:2092-8. 7. Cohen et al. NEJM 2011;365:493-505. 8. Schechter et al. JAIDS 2004;35:519-25. 9. Grant et al. NEJM 2010;363:2587-99 (MSM). 10. Mujugira et al. PLoS One 2011;6:e25828 (couples). 11. Paxton et al. Curr Opin HIV AIDS 2012;7:557-62 (heterosexuals). 12. Choopanya et al. Lancet. 2013;381:2083-90 (IDU). 13. Abdool Karim et al. Science 2010;329:1168-74.
Male circumcision 1-3 Treatment of STIs 4 HIV prevention Behavioural intervention HIV counselling and testing 5 Female condoms Male condoms Microbicides for women 13 Oral pre-exposure prophylaxis 9-12 MSM, couples, heterosexuals, IDUs Treatment for prevention 6,7 Post Exposure prophylaxis (PEP) 8 Note: PMTCT, screening transfusions, harm reduction, universal precautions, etc have not been included. This is focused on reducing sexual transmission. 1. Auvert et al. PLoS Med 2005;2:e298. 2. Gray et al. Lancet 2007;369:657-66. 3. Bailey et al. Lancet 2007;369:643-56. 4. Grosskurth et al. Lancet 2000;355:1981-7. 5. Sweat et al. Lancet. 2000;356:113-21. 6. Donnell et al. Lancet 2010;375:2092-8. 7. Cohen et al. NEJM 2011;365:493-505. 8. Schechter et al. JAIDS 2004;35:519-25. 9. Grant et al. NEJM 2010;363:2587-99 (MSM). 10. Mujugira et al. PLoS One 2011;6:e25828 (couples). 11. Paxton et al. Curr Opin HIV AIDS 2012;7:557-62 (heterosexuals). 12. Choopanya et al. Lancet. 2013;381:2083-90 (IDU). 13. Abdool Karim et al. Science 2010;329:1168-74.
PARTNER Study: Rate of HIV transmission according to sexual behaviour reported by the negative partner Rate of within couple transmission (per 100 CYFU) 0 1 2 3 4 HT Vaginal sex with ejaculation (CYFU=192) HT Vaginal sex (CYFU=272) Receptive anal sex with ejaculation (CYFU=93) MSM Receptive anal sex without ejaculation (CYFU=157) Insertive anal sex (CYFU=262) estimated rate 95% confidence interval Rodger, CROI 2014
AIDS Events Number of subjects experiencing >1 event Delayed Immediate Tuberculosis 34 (4%) 17 (2%) Serious bacterial infection 13 (1%) 20 (2%) WHO Stage 4 event 19 (2%) 9 (1%) Oesophageal candidiasis 2 2 Cervical carcinoma 2 0 Cryptococcosis 0 1 HIV-related encephalopathy 1 0 Herpes simplex, chronic 8 2 Kaposi s sarcoma 1 1 CNS Lymphoma 1 0 Pneumocystis pneumonia 1 0 Septicemia 0 1 HIV Wasting 2 0 Bacterial pneumonia 1 2
Edinburgh Melbourne
Naïve or Relapsers Treatment of HCV coinfection w or w/o HIV AASLD guidelines 2014 Eligible to Interferon Yes Yes PR + Sofo 12 w alt. [IB] No HCVG1 HCV G2 HCV G3 HCV G4 PR + Sime 24-48w [IIaC] Sofo + R [IB] Sofo + Sime + Riba [IIaC] Sofo + R (cirrh 16 w) [IB] Sofo + R 24 w [I B] PR+ Sofo 12 w [IIaB] PR + Sime 24-48w Sofo + R 24 w [IIaC] No Yes No Sofo + Sime + R [IIaC] PR + Sofo 12 w [IIaB] Sofo + R 12 w (16w cirrh.) [IB] PR + Sofo 12 w [IIaA] Sofo + R 24 w [IIaB] PR + Sofo 12 w [IIaB] Sofo + R 24 w [IIaC]
Treatment of HCV coinfection w or w/o HIV AASLD guidelines 2014 Naïve or Relapse rs Eligible to Interfer on Yes Yes 84.000 USD HCVG1 HCV G2 HCV G3 HCV G4 84.000 USD 54.000 USD 54.000 USD 168.000 No 138-168.000 USD 168.000 USD 84-102.000 USD USD No Yes 84.000 USD 138.000 USD No 168.000 USD 168.000 USD
Realizing the future..
Realizing the future..