- PDF Free Download

Global mortality from viral hepatitis (Cooke et al)

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.

Summary of EASL and AASLD 2014/2015 100 90 80 100% SVR24 (%) 70 60 50 40 30 20 10 0

INTEGRATED SUMMARY OF RESULTS: SVR12 TREATMENT NAIVE PATIENTS HCV/HIV coinfected HCV monoinfected All 100% 94,0% 94,8% 94,5% 96,6% 90,5% 94,1% 91,8% 94,2% 94,1% 75% SVR, % 50% 25% 0% 233 /248 478 /504 711 /752 28 /29 95 /105 123 /134 261 /277 573 /609 EBR/GZR EBR/GZR + RBV Total 834 /886 *Primary endpoint: SVR12 (HCV RNA <15 IU/mL)

INTEGRATED SUMMARY OF RESULTS: SVR12 TREATMENT EXPERIENCED PATIENTS HCV/HIV coinfected HCV monoinfected All 100% 100,0% 91,5% 100,0% 100,0% 91,8% 94,8% 94,9% 83,3% 93,4% 97,8% 97,8% 95,2% 93,9% 94,4% 94,5% 75% SVR, % 50% 210 /218* 210 /217* 139 /144 42 /44 27 /28 25% 0% 6/6 140 /153 146 /159 GZR/EBR 12 weeks 5/5 199 /210 204 /215 GZR/EBR+RBV 12 weeks 5/6 123 /131 128 /137 GZR/EBR 16-18 weeks* 4/4 132 /135 136 /139 GZR/EBR+RBV 16-18 weeks* 20 /21 594 /629 Total 614 /650 *HCV/HIV coinfected patients treated for 16 weeks and HCV monoinfected patients treated for 18 weeks

Do HIV+ respond differently to mono-infected patients? Karageorgopoulos, World J Hepatol, 2015; 7: 1936

Baseline characteristics GECCO Cohort: ledipasvir/sofosbuvir 8 weeks Overall (n=148) HCV (n=120) HIV-HCV (n=28) Male sex, n (%) 72 (49) 49 (41) 23 (82) <0.001 Median age [years] (IQR) 52 (44 58) 54 (45 62) 50 (42 62) 0.01 Transmission IVDU/MSM/blood, n (%) 46(31)/15(10)/ 36(24) 39(33)/1(1)/ 39(33) 7(25)/14(50)/ 0 p <0.01 HCV genotype 1/4, n (%) 144(97)/3(2) 120 (100) 24(86)/3(11) <0.001 Median HCV viral load [IU/mL] (IQR) 8.1x10 5 (2.5x10 5 1.7x10 6 ) 9x10 5 (3.4x10 5 1.7x10 6 ) 4.9x10 5 (8x10 4 9.8x10 5 ) Median ALT [U/L] (IQR) 56 (37 89) 53 (36 80) 78 (49 166) <0.01 Prior HCV treatment, n (%) 26 (18) 22 (18) 4 (14) ns Fibroscan >12.5kPa or APRI >2, n (%) 5 (3) 3 (3) 2 (7) HIV coinfection, n (%) 28 (19) 0 (0) 28 (100) Median CD4 cell count [/mm 3 ] (IQR) 531 (346 683) NA 531 (346 683) 8 weeks of LDV/SOF is not within label for cirrhosis, GT4 or prior treatment Ingiliz P et al. EACS 2015. Abstract PS7/5 0.01

Efficacy: SVR4 rates Sofosbuvir/ledipasvir for 8 weeks in real-life, SVR 4: 99% 100 80 SVR 4, % 60 40 20 0 104/105 14/14 4/4 1/1 16/16 10/10 Overall HIV-HCV F4 GT 4 pretreated High VL Metavir F4 defined as APRI > 2 OR Fibroscan > 12.5kPa, high VL load defined as > 2mio IU/ml (Abbott PCR) or 6 mio IU/ml (Roche PCR), prior treatment was interferon-based (in one case with sofosbuvir) 8 weeks of LDV/SOF is not within label for cirrhosis, GT4 or prior treatment Ingiliz P et al. EACS 2015. Abstract PS7/5

Efficacy: SVR12 rates Sofosbuvir/ledipasvir for 8 weeks in real-life, SVR 12: 98.5% 100 80 SVR12, % 60 40 20 0 69/70 7/7 3/3 12/12 9/9 Overall HIV-HCV F4 pretreated High VL Metavir F4 defined as APRI > 2 OR Fibroscan > 12.5kPa, high VL load defined as > 2mio IU/ml (Abbott PCR) or 6 mio IU/ml (Roche PCR), pretreatment was interferon-based (in one case with sofosbuvir) 8 weeks of LDV/SOF is not within label for cirrhosis, GT4 or prior treatment Ingiliz P et al. EACS 2015. Abstract PS7/5

HIV is a special population?

Treatment should be prioritized Treatment Indicated All naive and experienced pts with liver disease Prioritized Pts with fibrosis (F3) or cirrhosis (F4) including compensated cirrhosis HIV coinfection, HBV coinfection Indication for liver transplantation HCV recurrence after transplantation Extra-hepatic manifestations Debilitating fatigue Risk of transmitting HCV Justified Deferred Not recommended Pts with moderate fibrosis (F2) Pts with no or mild (F0-F1) disease and no extra-hepatic manifestations Pts with limited life expectancy due to non-liver comorbdities EASL Guidelines 2015. http://www.easl.eu/medias/cpg/hepc-2015/full-report.pdf.

Increased risk of cirrhosis and ESLD due to HIV/HCV co-infection 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. Clin Infect Dis. 2001;33:562-69.

HIV/HCV co-infection may result in multi-systemic disorders Global cognitive impairment Cognitive-motor impairment Dementia Peripheral neuropathy 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 E, et al. Curr HIV/AIDS Rep. 2011;8:12-22.

DIABETES

Drug drug interactions between HIV drugs and DAAs Key http://www.hiv-druginteractions.org/interactions.aspx (accessed October 2015)

Summary of EASL and AASLD 2014/2015 100 90 80 100% SVR24 (%) 70 60 50 40 30 20 10 0

Figure 2. Treatment Cascade for People with Chronic Hepatitis C Virus (HCV) Infection, Prevalence Estimates with 95% Confidence Intervals. Yehia BR, Schranz AJ, Umscheid CA, Lo Re V III (2014) The Treatment Cascade for Chronic Hepatitis C Virus Infection in the United States: A Systematic Review and Meta-Analysis. PLoS ONE 9(7): e101554. doi:10.1371/journal.pone.0101554 http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0101554

Figure 2. Treatment Cascade for People with Chronic Hepatitis C Virus (HCV) Infection, Prevalence Estimates with 95% Confidence Intervals.?100% Yehia BR, Schranz AJ, Umscheid CA, Lo Re V III (2014) The Treatment Cascade for Chronic Hepatitis C Virus Infection in the United States: A Systematic Review and Meta-Analysis. PLoS ONE 9(7): e101554. doi:10.1371/journal.pone.0101554 http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0101554

Figure 2. Treatment Cascade for People with Chronic Hepatitis C Virus (HCV) Infection, Prevalence Estimates with 95% Confidence Intervals.?5% DAA Yehia BR, Schranz AJ, Umscheid CA, Lo Re V III (2014) The Treatment Cascade for Chronic Hepatitis C Virus Infection in the United States: A Systematic Review and Meta-Analysis. PLoS ONE 9(7): e101554. doi:10.1371/journal.pone.0101554 http://journals.plos.org/plosone/article?id=info:doi/10.1371/journal.pone.0101554

New diagnosed HIV-positive MSM HCV uninfected (Ab-/RNA-) Susceptible treatmentnaive (Ab+/RNA-) Infection Acute HCV, spontaneous clearance (undiagnosed + diagnosed) Early HCV (<1 yr from infection), undiagnosed Early HCV (<1 yr from infection), Diagnosed New diagnosed HIV-positive MSM Chronic HCV (>1 yr from infection), undiagnosed Chronic HCV (>1 yr from infection), Diagnosed yr 1 Re-infection Early ( acute ) treatment Chronic, Diag yr 2+ Susceptible, treatmentexperienced Treatment failure Chronic treatment Also stratify by treatment naïve, IFN-experienced, DAA-experienced and low/high risk HIV and non-hiv death occurs from all states

Acute HCV among HIV+ MSM Canada: ~30 cases Prevalence chronic HCV/HIV 19%: 11.200 USA: 55 cases Prevalence chronic HCV/HIV 15 30%: 180.000 360.000 Lebanon: 1 case Prevalence chronic HCV/HIV 49%: 1.500 Europe: 1068 cases Prevalence chronic HCV/HIV 25%: 185.500 -UK 552 -Germany 157 -France 126 -Netherlands 97 -Belgium 69 -Swiss 23 -Italy 21 -Denmark 13 -Spain ~8 Taiwan: 28 cases Prevalence chronic HCV/HIV 5%: 8.800 Australia: 47 cases Prevalence chronic HCV/HIV < 1%: 1.000 http://www.eatg.org/

Social site and apps have made finding Chem-Sex easy and anonymous IDU or slamming has become more common place

The popularity of bareback sites

Results HCV detected in 20 (47%) of 43 specimens 2 invalid Median rectal VL 2.92 log10 IU/mL High correlation between magnitude of blood and rectal HCV VL 6 5 4 3 2 Rectal HCV VL (log 10 IU/mL) 1 0 (r = 0.689, p < 0.001) 2 4 6 Serum HCV VL (log 10 IU/mL) 8

No historic treatment in UK HCV chronic (RNA+) prevalence among HIV-diagnosed MSM(%) 20 18 16 14 12 10 8 6 4 2 0 CHRONIC PREVALENCE No historic treatment 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 HCV primary incidence among HIV-diagnosed MSM (/100py) 2,0 1,8 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 PRIMARY INCIDENCE 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 Martin NK et al, under review

HCV chronic (RNA+) prevalence among HIV-diagnosed MSM(%) 20 18 16 14 12 10 8 6 4 2 0 Current treatment rate with DAAs (90% SVR) from 2015 CHRONIC PREVALENCE Current treatment with DAAs 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 HCV primary incidence among HIV-diagnosed MSM (/100py) 2,0 1,8 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 PRIMARY INCIDENCE Current treatment with DAAs 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 Martin NK et al, under review

HCV chronic (RNA+) prevalence among HIV-diagnosed MSM(%) 20 18 16 14 12 10 8 6 4 2 0 Scale-up treatment for recent (80%) diagnoses with DAAs from 2015 CHRONIC PREVALENCE Scale-up treatment for recent diagnoses 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 HCV primary incidence among HIV-diagnosed MSM (/100py) 2,0 1,8 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 PRIMARY INCIDENCE Scale-up treatment for recent diagnoses 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 Martin NK et al, under review

HCV chronic (RNA+) prevalence among HIV-diagnosed MSM(%) 20 18 16 14 12 10 8 6 4 2 0 Scale-up treatment for recent (80%) & nonrecent diagnoses (20%/yr) with DAAs from 2015 CHRONIC PREVALENCE Scale-up treatment for recent AND nonrecent diagnoses 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 HCV primary incidence among HIV-diagnosed MSM (/100py) 2,0 1,8 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 PRIMARY INCIDENCE Scale-up treatment for recent AND nonrecent diagnoses 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 Martin NK et al, under review

Survival estimates Proportion free from reinfection 1.00 0.75 0.50 0.25 0.00 95% CI Previous spontaneous clearance 95% CI Previous SVR 0 2 4 6 8 Time at risk (years) Martin TC et al. AIDS 2013;27:2551 7

HCV re-infection incidence among HIV MSM changes over time 25 Re-infection incidence per 100py 20 15 10 5 0 2002 2008 2008 2014

Scale-up treatment for recent (80%) & nonrecent diagnoses (20%/yr) with DAAs and 20% behavioural risk reduction from 2015 HCV chronic (RNA+) prevalence among HIV-diagnosed MSM(%) 20 18 16 14 12 10 8 6 4 2 0 CHRONIC PREVALENCE Scale-up treatment AND behaviour change 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 HCV primary incidence among HIV-diagnosed MSM (/100py) 2,0 1,8 1,6 1,4 1,2 1,0 0,8 0,6 0,4 0,2 0,0 PRIMARY INCIDENCE Scale-up treatment AND behaviour change 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022 2024 Martin NK et al, under review

HCV risk among HIV- individuals 44 cases AHC identified by NEAT criteria 5 HCV Ab negative < 1 year 11 significant ALT rise 18 clinically diagnosed with AHC Mc Faul ICAAC 2014 McFaul K, et al. ICAAC 2014; Abstract V-676.

whocares