Christoph Boesecke, Patrick Ingiliz, Hans-Jürgen Stellbrink, Mark Nelson, Sanjay Bhagani, Marguerite Guiguet, Marc-Antoine Valantin, Thomas Reiberger, Martin Vogel, Jürgen K. Rockstroh, and the NEAT study group Abstract 49 Current treatment recommendations are: Consensus recommendation on treatment of acute hepatits C infection 1) Pegylated IFN and weight-based ribavirin is recommended for the treatment of acute hepatitis C in HIV infected patients (grade A, level II) Acute hepatitis C in HIV-infected individuals: recommendations from the European AIDS Treatment Network (NEAT) consensus conference The European AIDS Treatment Network (NEAT) Acute Hepatitis C Infection Consensus Panel Whether HCV genotype and addition of RBV leads to differences in treatment outcome in acute HCV with different genotypes in HIV co-infection remains unknown so far Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49.
Acute HCV was defined as (3 out of 4 within the preceding 4 months): Known or suspected exposure to HCV Detectable HCV-RNA (PCR) Documented seroconversion to positivity for anti-hcv IgG Serum alanine transferase of more than 35 U/l with a documented normal value within the preceding 12 months Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49. All n=33 GT 1/4 n=258 GT 2/3 n=45 p- value Duration of therapy* [%],96 24 weeks 61,2 59,3 73,3 48 weeks 38,5 4,7 26,7 Median time to treatment initiation [weeks] (IQR) 1 (4,9-16,7) 1 (4,9-17) 9,4 (4,9-14,5),567 Median time to first negative HCV RNA [weeks] (IQR) 8 (4-12) 8 (4-12) 5 (4-11),182 *Based upon discretion of investigator Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49.
% 1 9 7 5 4 3 2 1 p=,569 52.4 RVR 51.8 p=,835 66.7 SVR 69.6 11/21 118/228 2/3 19/273 pegifn mono pegifn/rbv Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49. % 1 9 7 5 4 3 2 1 p=,784 42.9 RVR 49.7 p=,9 7 SVR 66 6/14 99/199 14/2 157/238 pegifn mono pegifn/rbv Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49.
% 1 9 7 5 4 3 2 1 p=,571 71.4 RVR p=,16 65.5 SVR 94 5/7 19/29 6/1 33/35 pegifn mono pegifn/rbv Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49. No significant differences in total numbers or severity of adverse events Ribavirin dose reduction occurred in 1.2% of cases Interferon dose reduction occurred in 5.6% of cases Treatment was stopped in 17 patients (6%) due to toxicities Boesecke C, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 49.
Mark S. Sulkowski, Kenneth E. Sherman, Vincent Soriano, Jürgen K. Rockstroh, Douglas T. Dieterich, Pierre-Marie Girard, Mohammad Bsharat, Joshua Henshaw, Raymond A. Rubin, Varun Garg, Nathalie Adda Abstract 54 Part A: no ART T/ TVR + Pbo + SVR24 SVR12 1:1 48 (control) SVR12 SVR24 Part B: ART (EFV/TDF/FTC or ATV/r + TDF + FTC or 3TC) T/ 2:1 SVR12 Pbo + SVR12 48 (control) Weeks SVR24 TVR + 12 24 SVR24 36 48 72 EFV = efavirenz; TDF = tenofovir; FTC = emtricitabine; ATV/r = ritonavir-boosted atazanavir; 3TC = lamivudine; T/TVR = telaprevir 75 mg q8h or 1125 mg q8h (with EFV); Pbo=Placebo; P/Peg-IFN = pegylated interferon alfa-2a (4 kd) 1 µg/wk); SVR = sustained virologic response Sulkowski M, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 54.
Patients with SVR (%) 1 9 7 5 4 3 2 1 71 No ART EFV/TDF/FTC ATV/r/TDF/FTC Total 69 74 n/n = 5/7 11/16 12/15* 28/38 2/6 4/8* 4/8 1/22 T/ *Prior to Week 24 visit, 1 patient in this cohort was lost to follow up. SVR24 was imputed based on SVR12 for this patient. Sulkowski M, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 54. 33 5 5 45 n (%) T/ N=38 N=22 Severe rash () () Mild and moderate rash 13 (34) 5 (23) Any anemia (hemoglobin <1g/dL) 7 (18) 4 (18) Severe anemia (hemoglobin 7.-8.9 g/dl or decrease from baseline 4.5 g/dl) 11 (29) 5 (23) Use of erythropoietin stimulating agent 3 (8) 1 (5) Blood transfusions 4 (11) 1 (5) Discontinuation due to AE 3 (8) () No HIV breakthrough; CD4 counts declined in T/ and groups; CD4% unchanged 3 T/ patients discontinued due to adverse event (3 T/) Sulkowski M, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 54.
C max +ATV/r C avg C min +EFV C max C avg C min EFV: N=15 ATV/r: N=13 Geometric Least Squares Mean Ratio (9% CI) Sulkowski M, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 54. +ATV/r -TDF +TDF T/ +EFV +TDF -TDF 1 2 3 C trough Ratio: Median (25th-75th percentile) ATV/r: N = 7, N= 14 for T/ EFV: N = 8, N= 15 for T/ Sulkowski M, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 54.
Overall end of treatment (EOT), SVR12, and SVR24 rates (A,C), and relapse rates by week and between weeks and 72 (B,D) according to HCV genotype (AICOT) and RBV dosage (PARADIGM) in patients treated with PegIFN alfa-2a/rbv AICOT (A) 1 EOT (week 48) (B) 1 Patients with a virologic response (%) SVR12 (week ) 73 Early relapse (EOT to week ) SVR24 (week 72) 63 62 Late relapse (week to week 72) 4 4 28 28 4 31 2 2 13 1 1 n/n 71/176 49/176 5/176 69/95 /95 59/95 n/n 22/71 1/71 9/69 1/69 Genotype 1 Genotype 2/3 Genotype 1 Genotype 2/3 PARADIGM (C) (D) 1 1 EOT (week 48) Early relapse (EOT to week ) SVR12 (week ) SVR24 (week 72) Late relapse (week to week 72) Patients with a virologic response (%) 4 2 28 n/n 38/135 32 19 19 21 21 26/135 26/135 RBV mg/day 88/275 58/275 58/275 RBV 1/2 mg/day Sulkowski M, et al. 63rd AASLD; Boston, MA; November 9-13, 212; Abst. 54. Patients experiencing relapse (%) Patients experiencing relapse (%) 4 2 n/n 32 34 12/38 RBV mg/day 3/88 RBV 1/2 mg/day