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 yearsHCV infection

Genotype 1, 4, 6Treatment-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/mm3

Or naïve to ART and CD4 > 500/mm3 and

HIV RNA < 50,000 c/ml

Single armOpen-label

• Objective• SVR12 (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over historical reference rate of 70% (PHOTON-1 Study), with 1-sided 2.5% alpha level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

All patients (N = 218)Mean age, years 48.7Female 16%White / Black or African-American 77% / 17%Genotype 1a 1b 1 other 4 6

66%20%0.5%13%1%

HCV RNA log10 IU/ml, mean 6.03 ± 0.57HCV RNA > 800,000 IU/ml 58%Cirrhosis 16%IL28B CC 35%CD4/mm3, median 568On ART with undetectable HIV RNA 97%ART with

ABCTDFRALDTGRPV

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

C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection

Lost to follow-up or discontinuation unrelated to virologic failure

1 3 1 0

Breakthrough 0 0 0 0

Relapse 5 4 1 1

Re-infection 2 1 0 0

100

75

50

25

0

96.3(92.9-98.4) 94.4 95.5 96.4

All patients GT1a GT1b GT4

218 144 44 28

C-EDGE co-infection

SVR12 (HCV RNA < 15 IU/mL), % (95% CI)

%

Rockstroh JK. Lancet HIV 2015,July 10, online

C-EDGE co-infection study: grazoprevir/ elbasvir in HIV coinfection SVR12 by subgroups :

– No differences for key subgroups characteristics (gender, age, race, IL28B genotype, cirrhosis, baseline HCV RNA, RAL vs DTG vs RPV)

– ABC-containing : SVR12 = 93.6% vs TDF-containing : SVR12 = 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

C-EDGE co-infection study : grazoprevir/ elbasvir in HIV coinfection

All patients (N = 218)Serious adverse event 6* (2.8)

Serious drug-related adverse event 0 (0)

Discontinuation due to adverse event 0 (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

C-EDGE co-infection study : grazoprevir/ elbasvir in HIV coinfection

All patients (N = 218)

ALT grade 3 / grade 4 3 / 2

AST grade 3 / grade 4 0 / 1

Late ALT or AST > 5.0 x ULN (after end of treatment) 2 (0.9)

Hemoglobin < 9 g/dl on treatment 0

Elevation of total bilirubin

> 2.5 – 5.0 x baseline

> 5.0 x baseline

1

0

Creatinine > 2.5 x baseline 0 (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

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 SVR12 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