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Coinfezioni da HCV/HBV

This report examines the prevalence of HBsAg and HCVAb positivity in ICONA patients, their distribution based on gender and mode of HIV transmission, and the disease progression in HCV monoinfection versus HCV/HIV coinfection. It also discusses the evolution of HCV therapy and the efficacy of HCV Direct Acting Antivirals (DAAs) in persons with and without HIV coinfection.

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Coinfezioni da HCV/HBV

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  1. Coinfezioni da HCV/HBV Andrea Antinori INMI L. Spallanzani IRCCS

  2. HBsAg and HCVAbpositivity in ICONA patients Jan 2018 Report

  3. HBsAg and HCVAbpositivityaccording to gender in ICONA patients Jan 2018 Report

  4. HCVAb status according to mode of HIV transmission in 14.649 ICONA patients Jan 2018 Report

  5. HCVAbpos (n=3710) according to gender and mode of HIV transmission in 14.649 patientsenrolled in ICONA Jan 2018 Report

  6. HBsAgpositivityaccording to mode of HIV transmission in 14.264 ICONA patients Jan 2018 Report

  7. HBsAgpositivity (n=1024) according to gender and mode of HIV transmission in 14.264 ICONA patients Jan 2018 Report

  8. Proportion of patients with HCVAbpos test within 1 year from enrolment, according to calendaryear of enrolment Jan 2018 Report

  9. Proportion of patients with HCVAb positive test within 1 year from enrolment, according to calendaryear of enrolment and gender Jan 2018 Report

  10. Jan 2018 Report

  11. Jan 2018 Report

  12. Prevalence of HCV-RNA pos in HCVAbpospatients in ICONA Last HCV-RNA test N=104 N=1477 N=1699 Jan 2018 Report

  13. Proportion of HCV genotypes among 1.507 HCV-RNA+ patients in ICONA Jan 2018 Report

  14. Jan 2018 Report

  15. Disease Progression in HCV Monoinfection vs HCV/HIV Coinfection With or Without HIV Suppression Time to Decompensation by Maintained HIV RNA Level Time to Decompensation by Maintained CD4+ Cell Count Retrospective cohort study of HCV-infected, treatment-naive patients in the Veterans Health Administration (N = 10,359) 0.2 0.2 HCV-monoinfection • HCV/HIV coinfection with effective HIV therapy (HIV-1 RNA < 1000 copies/mL) • HCV/HIV coinfection without effective HIV therapy (HIV-1 RNA ≥ 1000 copies/mL) HCV-monoinfection • HCV/HIV coinfection with effective HIV therapy(CD4+ count < 0.200 x 109 cells/L) • HCV/HIV coinfection without effective HIV therapy • (CD4+ count ≥ 109 cells/L) Cumulative Incidenceof Hepatic Decompensation Cumulative Incidenceof Hepatic Decompensation 0.1 0.1 0.081 0.076 Slide credit: clinicaloptions.com 0.069 0.069 0.048 0.048 0 0 0 2 4 6 8 10 0 2 4 6 8 10 Yrs to Hepatic Decompensation Yrs to Hepatic Decompensation • If HIV-1 RNA < 1000 copies/mL: +65% excess risk • If HIV-1 RNA ≥ 1000 copies/mL: +82% excess risk • If CD4+ < 200/mm2: +203% excess risk • If CD4+ ≥ 200/mm2: +56% to 63% excess risk Lo Re III V, et al. Ann Intern Med. 2014;160:369-379.

  16. No Decline in ESLD Incidence in Persons With HCV/HIV Coinfection in the Modern ART Era ESLD Incidence in Persons With HIV Infection by Viral Hepatitis Coinfection Status 35 Early ART era (1996-2000) Middle ART era (2001-2005) Modern ART era (2006-2010) 30 25 ESLD Incidenceper 1000 Person-years 20 15 10 5 0 Not Assessed HBV-/HCV- HBV-/HCV+ HBV+/HCV- HBV+/HCV+ Klein MB, et al. Clin Infect Dis. 2016;63:1160-1167. 34,119 HIV-infected adults followed for 129,818 person-yrs; 380 incident ESLD outcomes occurred

  17. The Evolution of HCV Therapy Ledipasvir/ Sofosbuvir (GT1) Frequent curability of diverse populations without IFN Simeprevir + Sofosbuvir (GT1) Sofosbuvir/Velpatasvir/ Voxilaprevir (DAA failures, all genotypes) Ombitasvir/ Paritaprevir/RTV (GT4) + Dasabuvir (GT1) Daclatasvir + Asunaprevir (Japan) Daclatasvir + Sofosbuvir (Europe) Telaprevir and Boceprevir (GT1) Daclatasvir + Sofosbuvir (GT3) (2016: GT1) Sofosbuvir/ Velpatasvir (all genotypes) ? Interferon Era 2017 2016 2011 2012 2013 2014 2015 1991- Glecaprevir/ Pibrentasvir (all genotypes) Simeprevir or Sofosbuvir with IFN (GT1) Curability of HCV without IFN Grazoprevir/ Elbasvir (GT1,4) First approved IFN-free therapy: Sofosbuvir + RBV (GT2,3)

  18. HCV DAAs Have Similar Efficacy in Persons With and Without HIV Coinfection Efficacy Across Separate Phase III Studies of GT1-6 HCV InfectionWith GLE/PIB, GZR/EBR, SOF/LDV, or SOF/VEL SVR 95% to 99% HCV Monoinfection[1-4] N = 146 to 624 SVR 95% to 98% N = 106 to 335 HCV/HIV Coinfection[5-8] 1. Forns X, et al. Lancet Infect Dis. 2017;10:1062-1068. 2. Zeuzem S, et al. Ann Intern Med. 2015;163:1-13. 3. Afdhal N, et al. N Engl J Med. 2014;370:1889-1898. 4. Feld JJ, et al. N Engl J Med. 2015;373:2599-2607. 5. Rockstroh J, et al. IAS 2017. Abstract MOAB0303. 6. Rockstroh JK, et al. Lancet HIV. 2015;2:e319-e327. 7. Naggie S, et al. N Engl J Med. 2015;373:705-713. 8. Wyles D, et al. Clin Infect Dis. 2017;65:6-12. 60 100 0 40 80 20 SVR for HCV (%)* *Most data reported for these studies are from treatment-naive patients with GT1/4 HCV infection receiving 12-wk regimens.

  19. Treatment of HCV and HIV Infection in Persons With Coinfection • All persons with HIV should be treated with potent ART,especially those with HIV/HCV coinfection[1] • HIV infection is independently associated with HCV disease progression[2] • HCV treatment should also be a priority for persons with HCV/HIV coinfection[2] • Efficacy and adverse event rates of HCV DAAs among those with HCV/HIV coinfection are similar to those observed with HCV alone • Cotreatment “requires continued awareness and attention to the complex drug–drug interactions that can occur between DAAs and antiretroviral medications” 1. DHHS Guidelines. 2018. 2. AASLD/IDSA HCV Guidelines. 2017.

  20. AASLD/IDSA Recommendations for First-line HCV Treatment in HCV/HIV Coinfection • All options available QD • *If GT1a with BL NS5A RASs for EBR, 12 wks not recommended; can increase duration to 16 wks with RBV (alternative). †Some data to support 8 wks in GT1, but 8 wks not recommended in HCV/HIV coinfection. ‡If decompensated cirrhosis, do not use HCV protease inhibitors. §If BL Y93H RAS present in GT3, add RBV or consider SOF/VEL/VOX. ‖If also cirrhotic, increase duration to 12 wks. AASLD/IDSA HCV Guidelines. 2017.

  21. Cotreatment of HCV and HIV Coinfection: Factors to Consider • HCV workup if starting DAA • HCV Genotype • HCV RNA level • Staging of liver disease • Child-Pugh score • Endoscopy? • HCC screening • Previous DAAs, potential need for resistance testing • HBV status • HIV workup if starting/switching ART • HIV-1 RNA level • HLA*B-5701 status • CD4+ cell count • Resistance testing • All patients • CrCl • Non-ART, non-DAA comedications • Comorbidities 1. AASLD/IDSA HCV Guidelines. 2017.

  22. Common Scenarios for the Cotreatment of HCV and HIV Infection • Persons taking ART with HIV RNA suppression who plan to initiate HCV DAA therapy • Decisions: • Selection of HCV DAA regimen • Adjustment of ART to facilitate a specific DAA regimen • Persons not taking ART who plan to initiate HCV DAA therapy • Decision: • Which infection to treat first, or whether to start both treatments simultaneously

  23. Principles of ART Regimen Switching in Virologically Suppressed Patients • Review ART history for previous intolerance or HIV virologic failure • Review HIV resistance test results • If previous HIV resistance uncertain, consider a switch only if new regimen likely to maintain suppression of resistant virus • In patients with HBV/HIV coinfection, continue ARVs active against HBV (even if not needed for HIV suppression) • (TAF or TDF) plus (3TC or FTC) Check HIV-1 RNA during first 3 mos after switch to ensure suppression Monotherapy with boosted PI or INSTI not recommended My approach: Consider ≥ 4-wk adjustment before starting HCV DAAs to ensure ART is tolerated and effective DHHS Guidelines. 2018.

  24. GS-1992: SOF/LDV in HIV/HCV Coinfection After Switch to TAF-Based Regimens • Randomized, open-label phase IIIb trial • Switch to TAF-based regimen maintained HIV-1 RNA < 50 copies/mL in 95% of patients • D/C before Wk 8 for lack of efficacy (n = 1), no resistance to ART SVR12, % Wk 8 Wk 20 Switch toEVG/COBI/FTC/TAF (n = 74) Start SOF/LDV HIV-infected patients with HIV-1 RNA < 50 copies/mL on stable ART,eGFR ≥ 30 mL/min, GT1 HCV infection, no previous NS5A or NS5B DAA (N = 148) 99 Switch toRPV/FTC/TAF (n = 74) Start SOF/LDV 94 Ramgopal M, et al. AASLD 2017. Abstract LB-12. ClinicalTrials.gov. NCT02707601.

  25. Does Switching ART Affect Likelihood of HCV Cure? Real-world, single-center cohort study of HCV/HIV-coinfected patients treated with DAAs (N = 255)[1] Observational, multicenter, 3-year study of HCV/HIV coinfected patients treated with SOF/LDV (N = 166)[2] Change in ART Change in ART n/N = 57/57 n/N = 72/78 100 92.3 P = .15 P = .02 No Change in ART No Change in ART n/N = 95/96 n/N = 174/177 99 98.3 0 20 40 60 80 100 0 20 40 60 80 100 Patients Achieving SVR* (%) Patients Achieving SVR (%) *In subgroup of N = 153 where SVR was reported. 1. Falade-Nwulia O, et al. Hepatology. 2017;66:1402-1412. 2. Marks K, et al. CROI 2018. Abstract 604

  26. Cotreatment of HIV and HCV coinfection • For many patients, initiation of ART should be prioritized; however, HIV treatment and HIV-1 RNA suppression are not required before HCV DAAs • Treatment readiness for 8-12 wks of HCV DAAs may be different than for lifelong ART • HCV treatment and cure may serve to facilitate HIV care engagement • SVR may reduce the risk of drug-induced liver injury • If ART is initiated first, consider delaying HCV DAAs for 4-6 wks to confirm tolerability and HIV-1 RNA response AASLD/IDSA HCV Guidelines. 2017.

  27. HCV Care Continues Past Achievement of SVR Diagnosis Linkage to care Treatment Cure • Persons with advanced fibrosis (stage 3/4): • Counseling • Harm reduction(alcohol and obesity) • Surveillance for HCC • Persons at risk for infection: • Counseling • Harm reduction(injection and sex practices) • Surveillance for reinfection Falade-Nwulia O, et al. J Hepatol. 2017;66:267-269. AASLD/IDSA HCV Guidelines. 2017.

  28. Treatment of HCV and HIV Infection in Persons With Coinfection • All persons with HIV should be treated with potent ART, especially those with HCV • Despite ART, HIV infection is independently associated with HCV disease progression • HCV treatment should also be a priority for persons with HCV/HIV coinfection • Efficacy and adverse event rates for HCV DAAs among those with HCV/HIV coinfection are similar to those observed with HCV alone • Cotreatment requires continued awareness and attention to the complex DDIs that can occur between DAAs and ARV medications What do the guidelines recommend for HCV/HIV coinfection in patient scenarios that you specify? See our simple tool: Guidance on Cotreatment of HCV and HIV Infection

  29. Prevalence and outcomes of NAFLD in the general population and in PLWHIV

  30. Non invasive diagnostic tests for NAFLD

  31. Interaction potential of antiretroviral agents Inhibition/induction intestinal CYPs ordrugtransporters Inhibition/induction ofhepatic CYPs glucuronidation, ordrugtransporters PI/ritonavir PI/cobicistat EVG/cobicistat maraviroc rilpivirine tenofovirprodrugs Metabolism maraviroc rilpivirine dolutegravir raltegravir PI/ritonavir PI/cobicistat EVG/cobicistat efavirenz etravirine nevirapine Change gastric pH atazanavir rilpivirine Absorption Chelationwithmineralsupplements Excretion integraseinhibitors Inhibition of renal drugtransporters tenofovir dolutegravir cobicistat ritonavir perpetratordrugs victimdrugs adaptedfrom Roden DM et al. NatRev, 2002

  32. HCV Treatment Options in HCV/HIV Co-infectedPersons

  33. Drug-drugInteractionsbetweenDAAs and ARVs

  34. Hepatitis C Virus in the US: Gaps in Current Practice 100% 100 80 50% 60 43% Pts (%) 40 27% 20 17% 16% 9% 0 ChronicHCV Infected Diagnosedand Aware Access to Care HCV RNAConfirmed Liver Biopsy Prescribed HCVTreatment AchievedSVR n = 3,500,000 1,743,000 1,514,667 952,726 581,632 555,883 326,859 Yehia BR, et al. PLoSOne. 2014;9:e101554.

  35. Cascade of Care of HIV/HCV Co-Infected Patients in Amsterdam Description of care in 255 HIV/HCV co-infected patients from two large clinics in Amsterdam. The most frequently used regimens were LDV/SOF (55%), SOF+DCV (27%) and SOF+SMV (8%). HCV treatment cascade of care Pt refused treatment, n=7 Severe comorbidity, n=4 Health insurance issues, n=3 Pending Failed SVR12 Treatment initiation pending n= 8 100% 95% 94% 2* SVR12=99% (186/188) Elimination of HCV in the setting of HCV/HIV-coinfection can be achieved rapidly without the need to upscale resources or personnel Saris, EASL 2017, FRI-246

  36. Global HCV elimination as a therapeutic goal can seem daunting Think globally, act locally! Undiagnosed PWID Linkage to care Elderly Effective therapy Global HCVelimination Homeless HIV/HCVco-infected Screening Non-cirrhotics Decompensated cirrhotics LTFU Elimination as a public health problem: achievement of a measurable global target in relation to a specific disease. Continued actions are required to maintain and/or to advance the target LTFU: lost to follow-up; PWID: people who inject drugs

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