1 / 20

How to manage virologic non-responders, non-genotype 1, relapsers

How to manage virologic non-responders, non-genotype 1, relapsers IAS 2013, Session: HCV – Is your patient being left behind? New options and unmet needs., Kuala Lumpur, Malaysia J ürgen K. Rockstroh Department of Internal Medicine I University Hospital Bonn Germany.

cerise
Download Presentation

How to manage virologic non-responders, non-genotype 1, relapsers

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. How to manage virologic non-responders, non-genotype 1, relapsers IAS 2013, Session: HCV – Is your patient being left behind? New options and unmet needs., Kuala Lumpur, Malaysia Jürgen K. Rockstroh Department of Internal Medicine I University Hospital Bonn Germany

  2. Disclosureslide: Jürgen Rockstroh • Receiptofgrants/researchsupports: • Gilead • Receiptofhonorariaorconsultationfees: • Abbvie, Abbott, Bionor. BMS, Boehringer, Gilead, GSK, Janssen, Merck, Novartis, Tobira, ViiV

  3. Howto manage: Virologic non-respondersand relapsers

  4. EACS guidelines 2012

  5. Telaprevir + PegIFN + RBV in HIV/HCV Co-infected Patients with Virologic Failure on IFN + RBV Single Arm, Phase 2 Clinical Trial • Complete RVR8(HCV-RNA <15 IU/mL): 32 weeks PR phase (Total treatment: 48 weeks) • Partial RVR8(15 IU/mL <HCV-RNA <1,000 IU/mL) 56 weeks PR phase (Total treatment: 72 weeks) W16EVR16 D0 W4 W8RVR8 W48 W72SVR24 W96 Complete RVR8 PegIFN α-2aRBV Follow-up (Lead in)PegIFN α-2aRBV TelaprevirPegIFN α-2aRBV SVR24 PegIFN α-2aRBV Follow-up Partial RVR8 Cotte L, et al. 20th CROI; Atlanta, GA; March 3-6, 2013. Abst. 36.

  6. Main Inclusion Criteria Chronic HCV genotype 1 infection and HIV-1 infection Previous virological failure after ≥12 weeks PegIFN + RBV ≥600 mg/day Stable ART for ≥3 months Authorized antiretrovirals: ATV, ATVr, EFV, RAL, TDF, FTC, 3TC CD4 ≥200 cells/mm3 and ≥15%, plasma HIV-RNA levels <50 copies/mL Liver biopsy <3 years or cirrhosis on any previous biopsy Main Exclusion Criteria HVB coinfection, HIV-2 infection Past history of decompensated cirrhosis Previous null response with cirrhosis Important patient characteristics F3 16%, F4 23%; HCV GT1a 70% Telaprevir + PegIFN + RBV in HIV/HCV Co-infected Patients with Virologic Failure on IFN + RBV Cotte L, et al. 20th CROI; Atlanta, GA; March 3-6, 2013. Abst. 36.

  7. Virological response (ITT, n=69) RVR8 EVR16 88% TND Only 3 patients with partial RVR8  treatment 72 weeks

  8. Telaprevir + Peg-IFN + RBV in HIV/HCV co-infected patients with virologic failure on IFN + RBV: Early virologic response by patient group n= 12 34 27 30 13 6 11 12 15 16 10 21 RAL F1 F2 F3 F4 RR PR NR ATVr EFV Others BrkTh Cotte L, et al. 20th CROI; Atlanta, GA; March 3-6, 2013. Abstract 36

  9. Grade 3–4 AEs and treatment discontinuations up to W16

  10. Boceprevir + PegIFN + RBV for HIV-HCV Co-Infected Patients with Previous Virologic Failure on PegIFN + RBV SVR24 W72 W8-HCV VL < 15 IU/ mL: BOC+ PegIFN + RBV Follow-up Study Design SVR24 W96 Lead- in Phase W8-HCV VL > 1,000 IU/ mL: PegIFN + RBV Follow-up *PegIFN + RBV **BOC+ PegIFN + RBV W12-HCV VL> 1,000 IU/ mL: PegIFN + RBV W8 15≤HCV VL- ≤1,000 IU/mL BOC+ PegIFN + RBV Follow-up W12- 15< HCV VL≤ 1,000 IU/ mL BOC+ PegIFN + RBV PegIFN + RBV Follow-up 0 4 8 12 16 28 48 72 96 Weeks HCV VL > 1,000 IU/mL HCV RNA > 100 IU/mL HCV RNA Still Detectable * PegIFNα2b: 1.5 μg/kg/wk RBV: 800 to 1,400 mg/day ** BOC:800 mg 3 times/ day Stop BOC Stop All Drugs RVR8: % HCV RNA <15 IU/mL EVR16:% HCV RNA <15 IU/mL EPO, G-CSF, TPO-R agonistsallowed Pizot-Martin I, et al. 20th CROI; Atlanta, GA; March 3-6, 2013. Abst. 37.

  11. Inclusion/Exclusion Criteria • Inclusion • body weight 40-125 kg • Chronic HCV genotype 1 • Previous virologic failure on PegIFN + RBV • Stable antiretroviral therapy with 3 or more ARV agents among TDF, ABC, FTC, 3TC, ATV (boosted or not), and RAL • CD4+ count ≥200 cells/mm3 and VL <50 c/mL for ≥6 months • Any fibrosis level on liver bx within past 3 years or any bx showing cirrhosis • Exclusion • HBV co-infection • Childs B or C; decompensated cirrhosis • Previous null response with cirrhosis • Important patient characteristics • F4 17%; previous null responders 33%, GT1a 78% Pizot-Martin I, et al. 20th CROI; Atlanta, GA; March 3-6, 2013. Abst. 37.

  12. BOC/IFN/RBV following virologic failure: results by previous response to Peg-IFN + RBV RVR 8 EVR 16 Pizot-Martin I, et al. 20th CROI; Atlanta, GA; March 3–6, 2013. Abstract 37

  13. BOC/IFN/RBV following virologic failure: Results by ARV regimen RVR 8 EVR 16 Pizot-Martin I, et al. 20th CROI; Atlanta, GA, 2013; Abstract 37

  14. Management of HIV-HCV GT1-co-infected patients (chronic) according to prior treatment outcome Naive Relapser Nonresponder Individual decision Individual decision/triple therapy Defer F0F1 Triple therapy Triple therapy Individual decision according to disease progression F2F3 Triple therapy Triple therapy Triple therapy F4 Ingiliz P. & Rockstroh J. Liver Int 2012;32:1194–9; EACS guidelinesversion November 2012

  15. EACS guidelines 2012

  16. Howto manage: Non-genotype 1

  17. Pivotal RCTs for Peg-IFN/RBV in HIV/HCV co-infection 1. Carrat F, et al. JAMA 2004;292:2839–48; 2. Laguno M, et al. Hepatology 2009;49:22–31; 3. Chung RT, et al. N Engl J Med 2004;351:451–9; 4. Torriani FJ, et al. N Engl J Med 2004;351:438–50; 5. Núñez M, et al. AIDS Res Hum Retroviruses 2007;23:972–82

  18. EACS guidelines 2012

  19. PHOTON 1 and 2 Studies: GT1 or 4 HIV/HCV co-infected treatment-naïve (TN) and GT- 2/3 TN and Experienced Subjects with sofosbuvir + RBV 12-24 weeks Ongoing clinicaltrials in HIV/HCV coinfection

More Related