HIV/HCV co-infected patients should be prioritised for HCV treatment Sanjay Bhagani Royal Free Hospital/UCL London
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What should a prioritisation process Life-saving at this stage achieve? Cirrhosis/de-compensation events Post-transplant recurrence with rapid progression Extra-hepatic morbidity with immediate impact Maximum health-benefit impact for treatment now as opposed to in 2-3 years time For the individual Public Health
HIV+ respond similarly to mono-infected patients
Prioritisation of patients with advanced liver disease is fairly straightforward EASL Guidelines 2015
Risk of fibrosis progression/cirrhosis Ingiliz P and Rockstroh J, Curr Opin HIV, 2015
Liver-related Deaths EuroSIDA
Lo Re V et al. Ann Intern Med 2014;160:369 379 Standardised cumulative incidence of hepatic decompensation in the era of modern cart Cohort study, 4,280 cart-treated HIV/HCV co-infected and 6,079 HCV mono-infected patients in the Veterans Aging Cohort Study Virtual Cohort (1997 2010) 1 Cumulative Incidence of Decompensation Cumulative Incidence 0.2 0.1 0 ahr = adjusted hazard ratio HIV/HCV co-infected HCV mono-infected 0.074 0.048 0 1 2 3 4 5 6 7 8 9 10 Years to Hepatic Decompensation to Hepatic Decompensation Hepatic decompensation risk 83% higher in the co-infected group (ahr 1.83, 95% confidence interval [CI] 1.54 2.18) 1 p<0.001
Arends et al., J Hepatology 2015
HIV/HCV a contribution to multiple organ dysfunction 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 dysfunction 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 Impaired CD4 recovery post-haart Severe immunodeficiency Adapted from Operskalski EA and Kovacs A. Curr HIV/AIDS Rep 2011;8:12 22.
HCV increases overall and non-liver related mortality in HIV-infected patients In recent study, 2,385 out of 70,559 HIV-infected patients died in 248,885 patient-years Overall mortality was higher in 8,374 (7.5%) HIV/HCV patients compared with 60,016 (2.8%) HIV patients Non-liver-related as well as non-liver, non-aids-related mortality were higher in HIV/HCV coinfected patients (HR 1.40, P<0.0001 and HR 1.47, P<0.0001 respectively) Overall mortality Survival probability Months from January 2008 Mallet V et al. CROI 2014. Boston, MA. #690
Free-survival (%) SVR in HIV/HCV co-infected patients with mild Fibrosis A total of 695 HIV/HCV-co-infected patients were treated with IFN/RBV after a median follow-up of 4.9 years. 274 patients achieved an SVR 100 95 90 85 15 10 5 No SVR All-cause mortality SVR p=0.010 Patients with F0-F2 fibrosis Free-liver-related events (%) 100 95 90 85 p<0.001 15 10 5 Liver-related complications No SVR SVR Patients with F0-F2 fibrosis 0 0 12 24 36 48 60 72 84 96 Follow-up (months) 0 0 12 24 36 48 60 72 84 96 Follow-up (months) The achievement of an SVR after interferon-ribavirin therapy in patients co-infected with HIV/HCV and with mild Fibrosis reduces liver-related complications and mortality Adapted from Berenguer J et al. J Acquir Immune Defic Syndr 2014;66:280 287
Impact of SVR in HCV mono-infected Innes et al, Hepatology 2015
Sustained transmission of HCV amongst HIV+ MSM Swiss HIV Cohort Study: HCV yearly incidence rate by transmission group* HET IDU MSM Incidence rate (per 100 py) 20 15 10 0.1 5 1 1998 2000 2002 2004 2006 2008 2010 Calendar year *Shaded: 95% confidence intervals Euro Surveill. 2010;15(39):pii=19673. Adapted from Wandeler G, et al. CROI 2012. Poster Q106
HCV re-infection after SVR HCV-RNA clearence does not prevent reinfection after new exposure Five-year rate (95% CI) of recurrence post-svr, by risk group HCV re-infection negates the benefits of SVR The risk of re-infection is significant, in particular among IDUs and HIV co-infected patients¹ Uknown if IFN-free treatment, or earlier HCV treatment, increases the risk-compensation and thereby the risk of re-infection ¹Hill et al; abstract 654, CROI 2015
Treatment As Prevention for HCV in HIV+ MSM N Martin, et al EASL 2015, abstract P1289 (manuscript submitted)
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EASL Guidelines: HIV/HCV Patients Should be a Priority for Treatment Treatment priority Treatment is indicated Treatment should be prioritized Treatment is justified Treatment can be deferred Treatment is not recommended Patient group Treatment naive and treatment experienced, with compensated and decompensated liver disease Fibrosis (F3) or cirrhosis (F4) including decompensated cirrhosis HIV co-infection HBV co-infection Liver transplant HCV recurrence post-liver transplant Clinically significant extra-hepatic manifestations Debilitating fatigue Individuals at risk of transmitting HCV (IDU, MSM with high-risk sexual practices, women of child-bearing age wishing to get pregnant, hemodialysis patients, incarcerated patients) Moderate fibrosis (F2) No or mild disease (F0 F1) and none of the above mentioned extra-hepatic manifestations Limited life expectancy due to non-liver-related comorbidities MSM = men who have sex with men. EASL Recommendations on Treatment of Hepatitis C 2015 (accessed July 2015). Available at: http://www.easl.eu/research/our-contributions/clinical-practice-guidelines.