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C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection GZR/EBR 100/50 mg qd N = 218  Design W12 W24 C-EDGE co-infection Rockstroh JK. Lancet.

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Presentation on theme: "C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection GZR/EBR 100/50 mg qd N = 218  Design W12 W24 C-EDGE co-infection Rockstroh JK. Lancet."— Presentation transcript:

1 C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection GZR/EBR 100/50 mg qd N = 218  Design W12 W24 C-EDGE co-infection Rockstroh JK. Lancet HIV 2015,July 10, online > 18 years HCV infection Genotype 1, 4, 6 Treatment-naïve HCV RNA > 10,000 IU/mL Compensated cirrhosis* allowed HIV infection on stable ART** for ≥ 8 weeks and undetectable HIV RNA and CD4 > 200/mm 3 Or naïve to ART and CD4 > 500/mm 3 and HIV RNA < 50,000 c/ml Single arm Open-label Objective SVR 12 (HCV RNA < 15 IU/mL) by intention to treat analysis, 99% power to establish superiority over historical reference rate of 70% (PHOTON-1 Study), with 1-sided 2.5% alpha level ** TDF or ABC + 3TC or FTC + RAL or DTG or RPV * Metavir F4 or Fibroscan > 12.5 kPa or FibroTest > 0.75 + APRI > 2

2 All patients (N = 218) Mean age, years48.7 Female16% White / Black or African-American77% / 17% Genotype 1a 1b 1 other 4 6 66% 20% 0.5% 13% 1% HCV RNA log 10 IU/ml, mean6.03 ± 0.57 HCV RNA > 800,000 IU/ml58% Cirrhosis16% IL28B CC35% CD4/mm 3, median568 On ART with undetectable HIV RNA97% ART with ABC TDF RAL DTG RPV 22% 75% 52% 27% 17% Baseline characteristics C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection C-EDGE co-infection Rockstroh JK. Lancet HIV 2015,July 10, online

3 C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection Lost to follow-up or discontinuation unrelated to virologic failure 1310 Breakthrough0000 Relapse5411 Re-infection2100 100 75 50 25 0 96.3 (92.9-98.4) 94.495.596.4 All patientsGT1aGT1bGT4 2181444428 C-EDGE co-infection SVR 12 (HCV RNA < 15 IU/mL), % (95% CI) % Rockstroh JK. Lancet HIV 2015,July 10, online

4 C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection  SVR 12 by subgroups : –No differences for key subgroups characteristics (gender, age, race, IL28B genotype, cirrhosis, baseline HCV RNA, RAL vs DTG vs RPV) –ABC-containing : SVR 12 = 93.6% vs TDF-containing : SVR 12 = 97.6%  Relapse, n = 5 –All non-cirrhotic, genotype 1a, N = 4 ; genotype 4, N = 1 –4/5 were receiving ART : TDF-based ART N = 3; ABC-based ART N = 1  Re-infection, n = 2 –The 2 patients were infected with a different HCV genotype during follow- up compared with baseline : Genotype 1a and Genotype 1b at enrolment ; Genotype 3 at follow-up W12 in both –Per protocol, these patients were classified as a failure for analysis, but sequencing data are consistent with post-treatment re-infection C-EDGE co-infection Rockstroh JK. Lancet HIV 2015,July 10, online

5 C-EDGE co-infection study : grazoprevir/ elbasvir in HIV coinfection All patients (N = 218) Serious adverse event6* (2.8) Serious drug-related adverse event0 (0) Discontinuation due to adverse event0 (0) Adverse event in > 5% of patients Fatigue Headache Nausea Upper respiratory tract infection Diarrhea Insomnia 29 (13.3) 27 (12.4) 20 (9.2) 17 (8) 16 (7) 15 (7) Drug-related adverse events in > 5% of patients Fatigue Headache 16 (7) 15 (7) Adverse events, N (%) C-EDGE co-infection * convulsion, pneumonia, erysipela, acute psychosis and urinary retention, ulnar fracture, spontaneous bacterial peritonitis Rockstroh JK. Lancet HIV 2015,July 10, online

6 C-EDGE co-infection study : grazoprevir/ elbasvir in HIV coinfection All patients (N = 218) ALT grade 3 / grade 43 / 2 AST grade 3 / grade 40 / 1 Late ALT or AST > 5.0 x ULN (after end of treatment)2 (0.9) Hemoglobin < 9 g/dl on treatment0 Elevation of total bilirubin > 2.5 – 5.0 x baseline > 5.0 x baseline 1010 Creatinine > 2.5 x baseline0 (0) Laboratory abnormalities (treatment period plus first 14 days of follow-up), N (%) C-EDGE co-infection Rockstroh JK. Lancet HIV 2015,July 10, online

7 C-EDGE co-infection study : grazoprevir/ elbasvir in HIV coinfection C-EDGE co-infection  Summary –A 12-week regimen of the oral fixed dose combination of once-daily, single-tablet of grazoprevir/elbasvir, achieved an overall SVR 12 of 96% in patients with HCV genotype 1 or 4 infection and HCV co-infection Comparable response rates to HCV mono-infected genotype 1 and 4 Comparable SVR across all patients sub-groups –Low rate of adverse events –HIV breakthrough 2 patients with transient viremia and subsequent re-suppression with no change in ARV regimen No change in CD4+ cell counts –Limitation No active-control group Rockstroh JK. Lancet HIV 2015,July 10, online

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