- Email: [email protected]
Retreatment of HCV DAA Failures: HCV Infection may be Incurable
POSTER PRESENTATIONS Results: The ASTRAL studies enrolled a diverse population of HCV with 35 known subtypes and 13 novel/mixed subtypes including 1 GT7 patient. Overall the prevalence of NS5A RAVs and NS5B RAVs was 36% and 7%, respectively. In patients with and without cirrhosis receiving SOF/VEL for 12 weeks in the ASTRAL-1-3 studies, high SVR12 rates were observed in patients with baseline NS5A RAVs (97–100% in GT1-2, 4–6 and 88% in GT3) (Table 1). Overall, the virologic failure rate was low (13/1028, 1.3%; 2 GT1; 10 GT3; 1 reinfection). The 2 GT1 infected patients who relapsed had NS5A Y93H or Y93N emerge. Within the GT3 patients with relapse, 6 had Y93H emerge and 4 maintained/enriched this baseline variant. SVR12 was achieved in all 77 patients who had baseline NS5B NI RAVs. No NS5B resistance was observed in patients with virologic failure. Table 1: SVR12 in Patients with or Without Baseline NS5A RAVs by HCV Genotype (SOF/VEL 12 Weeks; ASTRAL-1-3). Baseline NS5A RAVs SVR12 in Patients Without NS5A RAVs, %, (n/N) SVR12 in Patients Without NS5A RAVs, %, (n/N)
GT1
GT2
GT3
GT4
GT5
GT6
TOTAL
97.3% (73/ 75)
100%
88.4% (38/ 43)
100% (72/ 72)
100% (6/ 6)
100% (22/ 22)
98% (373/ 380)
97.0%
100% (43/ 43)
100% (28/ 28)
100% (20/ 20)
99% (637/ 643)
100% (251/ 251)
(162/ 162) 100% (70/ 70)
(225/ 231)
In ASTRAL-4, SVR12 rates were 100% (19/19) and 98% (46/47) in GT1 patients with or without baseline NS5A RAVs treated for 12 weeks with SOF/VEL+RBV and were lower in GT1 patients with baseline NS5A RAVs who received SOF/VEL for 12 (80%) or 24 (90%) weeks. Of note, resistance in Child Pugh B patients experiencing virologic failure with SOF/VEL ± RBV was similar to ASTRAL-1-3. Conclusions: SOF/VEL for 12 weeks resulted in high SVR in GT1-6 infected patients irrespective of baseline NS5A RAVs. NS5A resistance, but not SOF-resistance, was detected in patients with virologic failure. Similar results were observed in patients with Child Pugh B cirrhosis treated with SOF/VEL + RBV. THU-217 RETREATMENT OF HCV DAA FAILURES: HCV INFECTION MAY BE INCURABLE C. Hezode1, S. Fourati2, G. Scoazec1, A. Soulier2, A. Varaut1, M. Francois1, I. Ruiz2, A. Mallat1, S. Chevaliez2, J.-M. Pawlotsky2. 1 Hepatology; 2Virology, Hôpital Henri Mondor, Créteil, France E-mail: [email protected] Background and Aims: Current EASL recommendations suggest that patients who failed on a DAA-containing regimen should be retreated with an IFN-free combination including sofosbuvir (SOF), plus one or two other direct-acting antiviral (DAAs), ideally with no crossresistance with the DAAs already administered. The goal of this pilot experience was to evaluate the efficacy and safety of a triple combination of SOF + daclatasvir (DCV) + simeprevir (SMV) with
ribavirin RBV) for 24 weeks in patients who previously failed on a DAA combination administered 12 weeks without RBV. Methods: Eight patients (mean age: 56.2 years, range: 48–64) infected with HCV genotype 1 (1a: n = 4 ; 1b: n = 2) ; 4 (n = 1) or 6 (n = 1) with compensated liver disease (fibroscan: 6.6–35.3 kPa) who failed to achieve SVR were included. They had received SOF + DCV (n = 3); SOF + SMV (n = 2); SOF + LDV (n = 1); GRZ + EBV (n = 1); Mericitabine + Danoprevir + ritonavir (n = 1); without RBV for 12 weeks. HCV RNA levels were measured with Abbott RealTime Assay (LLOQ/LOD: 12 IU/mL). HCV resistance was assessed at retreatment baseline by means of population sequencing of the NS3 protease, NS5A and NS5B polymerase coding regions. Antiviral efficacy was assessed monthly during treatment and at post treatment weeks 4 and 12. Results: The table shows the outcomes. One patient relapsed post-treatment and one patient discontinued early (week 4) due to the occurrence of a SAE ( pulmonary arterial hypertension). Two patients achieved SVR4. The remaining 4 patients are still on treatment. Conclusions: The combination of SOF + DCV + SMV + RBV for 24 weeks was associated with on-treatment response in all patients. However, at least 2 patients failed to achieve an SVR, one due to SAE, the other one due to post-treatment relapse. Given the lack of other DAA class options, the latter patients should be considered incurable. SVR12 data from the full series of patients will be presented. THU-218 AVDLIB 2: NEWS DIRECT-ACTING ANTIVIRAL (DDA) IN HCV PATIENTS WITH ADVANCED LIVER DISEASE. FINAL RESULTS OF A THE SECOND MULTICENTER PROSPECTIVE OBSERVATIONAL STUDY IN REAL LIFE PRACTICE IN FRANCE D. Ouzan1, G. Penaranda2, P. Delasalle3, C. Renou4, M. Antoni5, P. Toulemonde6, P. Halfon2,7, S. Bresson-Hadni8, J. Liautard 9, M. Bourlière10. 1Institut Arnault Tzanck, Saint Laurent du Var; 2 Laboratoire Alphabio, Marseille; 3Clinique du Palais, Grasse; 4CH Hyer̀ es, Hyer̀ es; 5Private Practice, Orange; 6Clinique St-Jean Languedoc, Toulouse; 7Hôpital Européen, Marseille; 8Private Practice, Besançon; 9 Private Practice, Saint Jean de Védas; 10Hôpital Saint-Joseph, Marseille, France E-mail: [email protected] Background and Aims: Data on direct-acting antivirals (DAA) therapy in real-life practice are limited. This study consisted in the second phase of a national cohort of HCV infected patients (AVDLIB2) that were treated with the news direct-acting antiviral (DAAs). The aim of AVDLIB2 study was to evaluate the results of these new DAAs in real life practice. Methods: Data were prospectively collected on 213 patients recruited from November 2014 to August 2015. There were 57% males; mean age was 61 ± 11 years; most of them were treated according to fibrosis criteria F3 (45%) and F4 (43%); 31% were naive; 6% were HIV coinfected; 18% had comorbidity (alcohol, diabetes, or arterial hypertension). There were 22% genotype 1a, 29% genotype 1b, 31% genotype 1 undetermined, 3% genotype 2, 7% genotype 3, 7%
Table (abstract: THU-217). Genotype
Baseline RAVs
Week 4HCV RNA (UI/mL)
Last on-treatment HCV RNA (UI/mL)
SVR4
1a 1a
R155K, D168E, M28A, Q30K R155K, Q30K
28 <12
<12 (EOT) <12 (week 4)
SVR4 NA
1a 1a 1b 1b 6 4a/c/d
Q30K M28T P58S,Y93H, S556G L31F, C316N V36I, Y56H, D168C D168E, L28M, L30C, L159F
<12 45 <12 15 <12 506
<12 (week 8) <12 (week 20) <12 (week 16) <12 (EOT) <12 (EOT) 56 (week 8)
Pending Pending Pending SVR4 SVR4 Pending
S400
Journal of Hepatology 2016 vol. 64 | S213–S424
SVR12 Relapse Discontinuation due to SAE Pending Pending Pending Pending Pending Pending
RAVs at failure R155K, D168E, M28A, Q30K R155K, M28T, Q30K
GT1
GT2
GT3
GT4
GT5
GT6
TOTAL
97.3% (73/ 75)
100%
88.4% (38/ 43)
100% (72/ 72)
100% (6/ 6)
100% (22/ 22)
98% (373/ 380)
97.0%
100% (43/ 43)
100% (28/ 28)
100% (20/ 20)
99% (637/ 643)
100% (251/ 251)
(162/ 162) 100% (70/ 70)
(225/ 231)
In ASTRAL-4, SVR12 rates were 100% (19/19) and 98% (46/47) in GT1 patients with or without baseline NS5A RAVs treated for 12 weeks with SOF/VEL+RBV and were lower in GT1 patients with baseline NS5A RAVs who received SOF/VEL for 12 (80%) or 24 (90%) weeks. Of note, resistance in Child Pugh B patients experiencing virologic failure with SOF/VEL ± RBV was similar to ASTRAL-1-3. Conclusions: SOF/VEL for 12 weeks resulted in high SVR in GT1-6 infected patients irrespective of baseline NS5A RAVs. NS5A resistance, but not SOF-resistance, was detected in patients with virologic failure. Similar results were observed in patients with Child Pugh B cirrhosis treated with SOF/VEL + RBV. THU-217 RETREATMENT OF HCV DAA FAILURES: HCV INFECTION MAY BE INCURABLE C. Hezode1, S. Fourati2, G. Scoazec1, A. Soulier2, A. Varaut1, M. Francois1, I. Ruiz2, A. Mallat1, S. Chevaliez2, J.-M. Pawlotsky2. 1 Hepatology; 2Virology, Hôpital Henri Mondor, Créteil, France E-mail: [email protected] Background and Aims: Current EASL recommendations suggest that patients who failed on a DAA-containing regimen should be retreated with an IFN-free combination including sofosbuvir (SOF), plus one or two other direct-acting antiviral (DAAs), ideally with no crossresistance with the DAAs already administered. The goal of this pilot experience was to evaluate the efficacy and safety of a triple combination of SOF + daclatasvir (DCV) + simeprevir (SMV) with
ribavirin RBV) for 24 weeks in patients who previously failed on a DAA combination administered 12 weeks without RBV. Methods: Eight patients (mean age: 56.2 years, range: 48–64) infected with HCV genotype 1 (1a: n = 4 ; 1b: n = 2) ; 4 (n = 1) or 6 (n = 1) with compensated liver disease (fibroscan: 6.6–35.3 kPa) who failed to achieve SVR were included. They had received SOF + DCV (n = 3); SOF + SMV (n = 2); SOF + LDV (n = 1); GRZ + EBV (n = 1); Mericitabine + Danoprevir + ritonavir (n = 1); without RBV for 12 weeks. HCV RNA levels were measured with Abbott RealTime Assay (LLOQ/LOD: 12 IU/mL). HCV resistance was assessed at retreatment baseline by means of population sequencing of the NS3 protease, NS5A and NS5B polymerase coding regions. Antiviral efficacy was assessed monthly during treatment and at post treatment weeks 4 and 12. Results: The table shows the outcomes. One patient relapsed post-treatment and one patient discontinued early (week 4) due to the occurrence of a SAE ( pulmonary arterial hypertension). Two patients achieved SVR4. The remaining 4 patients are still on treatment. Conclusions: The combination of SOF + DCV + SMV + RBV for 24 weeks was associated with on-treatment response in all patients. However, at least 2 patients failed to achieve an SVR, one due to SAE, the other one due to post-treatment relapse. Given the lack of other DAA class options, the latter patients should be considered incurable. SVR12 data from the full series of patients will be presented. THU-218 AVDLIB 2: NEWS DIRECT-ACTING ANTIVIRAL (DDA) IN HCV PATIENTS WITH ADVANCED LIVER DISEASE. FINAL RESULTS OF A THE SECOND MULTICENTER PROSPECTIVE OBSERVATIONAL STUDY IN REAL LIFE PRACTICE IN FRANCE D. Ouzan1, G. Penaranda2, P. Delasalle3, C. Renou4, M. Antoni5, P. Toulemonde6, P. Halfon2,7, S. Bresson-Hadni8, J. Liautard 9, M. Bourlière10. 1Institut Arnault Tzanck, Saint Laurent du Var; 2 Laboratoire Alphabio, Marseille; 3Clinique du Palais, Grasse; 4CH Hyer̀ es, Hyer̀ es; 5Private Practice, Orange; 6Clinique St-Jean Languedoc, Toulouse; 7Hôpital Européen, Marseille; 8Private Practice, Besançon; 9 Private Practice, Saint Jean de Védas; 10Hôpital Saint-Joseph, Marseille, France E-mail: [email protected] Background and Aims: Data on direct-acting antivirals (DAA) therapy in real-life practice are limited. This study consisted in the second phase of a national cohort of HCV infected patients (AVDLIB2) that were treated with the news direct-acting antiviral (DAAs). The aim of AVDLIB2 study was to evaluate the results of these new DAAs in real life practice. Methods: Data were prospectively collected on 213 patients recruited from November 2014 to August 2015. There were 57% males; mean age was 61 ± 11 years; most of them were treated according to fibrosis criteria F3 (45%) and F4 (43%); 31% were naive; 6% were HIV coinfected; 18% had comorbidity (alcohol, diabetes, or arterial hypertension). There were 22% genotype 1a, 29% genotype 1b, 31% genotype 1 undetermined, 3% genotype 2, 7% genotype 3, 7%
Table (abstract: THU-217). Genotype
Baseline RAVs
Week 4HCV RNA (UI/mL)
Last on-treatment HCV RNA (UI/mL)
SVR4
1a 1a
R155K, D168E, M28A, Q30K R155K, Q30K
28 <12
<12 (EOT) <12 (week 4)
SVR4 NA
1a 1a 1b 1b 6 4a/c/d
Q30K M28T P58S,Y93H, S556G L31F, C316N V36I, Y56H, D168C D168E, L28M, L30C, L159F
<12 45 <12 15 <12 506
<12 (week 8) <12 (week 20) <12 (week 16) <12 (EOT) <12 (EOT) 56 (week 8)
Pending Pending Pending SVR4 SVR4 Pending
S400
Journal of Hepatology 2016 vol. 64 | S213–S424
SVR12 Relapse Discontinuation due to SAE Pending Pending Pending Pending Pending Pending
RAVs at failure R155K, D168E, M28A, Q30K R155K, M28T, Q30K