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No HBV or HIV co-infection

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Presentation on theme: "No HBV or HIV co-infection"— Presentation transcript:

1 No HBV or HIV co-infection
ARV-trial.com AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1 Design 2-steps Randomisation* Open-label W8 W12 W24 N = 80 PTV150/r + OBV + DSV + RBV 18-70 years Chronic HCV infection Genotype 1 HCV RNA ≥ 50,000 IU/ml Treatment-naïve or null responders No cirrhosis No HBV or HIV co-infection N = 41 PTV150/r + DSV + RBV N = 39 PTV100/r + OBV + RBV N = 40 PTV200/r + OBV + RBV N = 79 Cohort 1 Naïve PTV150/r + OBV + DSV N = 39 PTV100/r + OBV + DSV + RBV N = 40 PTV150/r + OBV + DSV + RBV * Randomisation was stratified on genotype subtype (1a or 1b) and IL28 (CC or non-CC) N = 40 PTV100/r + OBV + DSV + RBV N = 40 PTV150/r + OBV + DSV + RBV Co-formulated paritaprevir/rironavir (PTV/r) : 100/100 or 150/100 or 200/100 mg qd Ombitasvir (OBV) : 25 mg qd Dasabuvir (DSV) : 400 mg bid RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) AVIATOR Kowdley KV. NEJM 2013; 370:222-32 1

2 or null responders (NR) No HBV or HIV co-infection
ARV-trial.com AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1 Design Randomisation* 2 : 1 : 1 : 1 : 1 Open-label W12 W24 18-70 years Chronic HCV infection Genotype 1 HCV RNA ≥ 50,000 IU/ml Treatment-naïve or null responders (NR) No cirrhosis No HBV or HIV co-infection N = 45 PTV200/r + OBV + RBV N = 23 PTV100/r + OBV + DSV + RBV N = 22 PTV150/r + OBV + DSV + RBV N = 23 Cohort 2 Prior NR PTV100/r + OBV + DSV + RBV N = 20 PTV150/r + OBV + DSV + RBV * Randomisation was stratified on genotype subtype (1a or 1b) and IL28 (CC or non-CC) Co-formulated paritaprevir/rironavir (PTV/r) : 100/100 or 150/100 or 200/100 mg qd Ombitasvir (OBV) : 25 mg qd ; Dasabuvir (DSV) : 400 mg bid RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) Objective Primary analysis : SVR24 with two-sided 95% CI, of naïve patients PTV150/r + OBV + DSV + RBV 8 weeks vs 12 weeks, 80% power to detect a 24% difference between groups (mITT analysis) AVIATOR Kowdley KV. NEJM 2013; 370:222-32 2

3 Baseline characteristics and patient disposition
ARV-trial.com AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1 Baseline characteristics and patient disposition Treatment-naïve N = 438 Null responders N = 133 Mean age, years 50.1 51.1 Female 47% 38% Race : black 14% Genotype 1a 68% 61% IL28B genotype CC 28% 3% HCV RNA log10 IU/ml, mean 6.53 6.64 HOMA-IR ≥ 3 25% 30% Fibrosis score ≥ F2 29% 50% Discontinued treatment, N (%) 24 (5.5%) 5 (3.8%) Adverse event Withdrew consent Lost to follow-up Other 0 3 8 13 1 4 AVIATOR Kowdley KV. NEJM 2013; 370:222-32 3

4 SVR24 (HCV RNA < 25 IU/ml)
ARV-trial.com AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1 SVR24 (HCV RNA < 25 IU/ml) PTV/r + OBV + DSV + RBV 8W PTV/r + OBV + DSV 12W PTV/r + OBV + RBV 12W PTV/r + OBV + DSV + RBV 12W PTV/r + OBV + DSV + RBV 24W 25 50 100 75 88 83 % 89 96 91 93 95 N 80 41 79 45 43 Treatment-naïve Null response to prior treatment SVR24 in naïve cohort genotype 1a (76-94%) vs 1b (96-100%); odds ratio : [p = ]) AVIATOR Kowdley KV. NEJM 2013; 370:222-32 4

5 Comparator Group vs Group 5 Difference in rate of SVR24 (95 % CI)
AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1 Comparison of SVR24 in Treatment-Naïve Patients, according to treatment Regimens Comparison SVR24 p Comparator Group vs Group 5 Difference in rate of SVR24 (95 % CI) Group 1 vs Group 5 8 W vs 12 W 88% vs 96% 0,08 Group 2 vs Group 5 Contribution of OBV 83% vs 96% 0,06 Group 3 vs Group 5 Contribution of DSV 89% vs 96% 0,09 Group 4 vs Group 5 Contribution of RBV Group 6 vs Group 5 24 W vs 12 W 91% vs 96% 0,24 Group 5 better Comparator group better -30 -20 -10 10 AVIATOR Kowdley KV. NEJM 2013; 370:222-32

6 AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1
Resistance emergence No variants at relapse in 7/10 patients in the 8-week groups In the 12-week and 24-week groups, 31/32 samples at breakthrough or relapse showed emergence of resistant variants. Most common : NS3 : position 168 NS5A : positions 28 and 30 NS5B : position 556 AVIATOR Kowdley KV. NEJM 2013; 370:222-32

7 AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1
Adverse events Treatment-Naïve Null responder Treatment group P/r/O/D/R-8 P/r/D/R-12 P/r/O/R-12 P/r/O/D-12 P/r/O/D/R-12 P/r/O/D/R-24 Discontinuation due to AE 1 2 3 Serious AE Common AE (> 20%) Fatigue Headache Nausea Insomnia Diarrhea Asthenia Cough 36% 35% 15% 12% 10% 9% 15% 32% 32% 17% 20% 24% 2% 12% 28% 29% 11% 14% 19% 8% 16% 6% 3% 27% 13% 4% 38% 36% 25% 33% 18% 22% 7% 21% P/r : co-formulated paritaprevir/rironavir : 100/100 or 150/100 or 200/100 mg qd O : ombitasvir ; D : dasabuvir ; R : ribavirin; 8 : 8 weeks ; 12 : 12 weeks ; 24 : 24 weeks Grade 3-4 laboratory abnormalities Grade 3 elevation of bilirubin, n = 11 (2%) with no concomitant AST/ALT elevation Grade 3 ALT elevation, n = 5 (1%), Grade 3-4 Triglycerides, n = 7 (1%), Anemia : 5% AVIATOR Kowdley KV. NEJM 2013; 370:222-32

8 ARV-trial.com AVIATOR Study: paritepravir/ritonavir + ombitasvir + dasabuvir + ribavirin in genotype 1 Summary In this phase IIb study, all-oral regimens of antiviral agents and RBV were effective both in non-cirrhotic patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy Rates of SVR24 ranged from 83% to 100% Among previously untreated patients, the rate of treatment failure was lower among those receiving the triple combination of paritaprevir/ritonavir + ombitasvir + dasabuvir + RBV for 12 weeks than among those who received the same regimen for 8 weeks and among those who received fewer agents; extending the treatment to 24 weeks offered no further benefit Higher number of relapses in 3D + RBV 8 weeks vs 12 weeks Paritaprevir/ritonavir + ombitasvir + dasabuvir + RBV for 12 weeks was associated with SVR24 of 93% in null responders to prior therapy For genotype 1b, all regimens led to SVR24 of 94%-100% with only 1/24 relapse in the 8-week group AVIATOR Kowdley KV. NEJM 2013; 370:222-32 8

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