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Results of hepatitis C treatment program among people who inject drugs
POSTER PRESENTATIONS Conclusions: Viral eradication doesn’t seem to be associated with increased risk of drop-out due to neoplastic disease-progression in HCV-HCC patients awaiting LT. Therefore, DAAs treatment can be safely offered to this patients population. SAT-270 Results of hepatitis C treatment program among people who inject drugs S. Filippovych1, O. Burgay1, I. Pavlyiuk1. 1TPSM, ICF “Alliance for Public Health”, Kyiv, Ukraine E-mail: [email protected] Background and Aims: According to WHO data in Ukraine, the approximate hepatitis C (HCV) infection rate among general population is 8.9% (which constitutes over 3.5 million individuals). An estimated number of people who inject drugs (PWID) in Ukraine is 310,000. HCV prevalence among PWID in Ukraine reaches 55%. HCV/HIV co-infection is registered in 38.4% of all newly registered HIV cases. Methods: Starting from June 2015, ICF “Alliance for Public Health” with support of the Ministry of Health of Ukraine organized HCV treatment program with direct-active antiviral – sofosbuvir (SOF) for HCVinfected PWID and representatives of other vulnerable populations using community-involved model (CIM) of treatment provision. HCV treatment was arranged in 19 healthcare facilities (HCFs) in 16 regions of Ukraine in collaboration with 15 non-governmental organizations. Multidisciplinary team (doctor/nurse/case-manager) was formed at each HCF. Within the CIM, case-managers provide support and links to integrated services (diagnostic and treatment of HIV, opioid substitution therapy (OST), and prevention of HCV re-infection). Results: As of November 1 2016, overall 1203 patients were enrolled in HCV treatment, 80% (N = 964) of them are PWID. 79% (N = 761) of all PWID were co-infected HCV/HIV, 97% (N = 737) received antiretroviral therapy (ARV), fibrosis stage in 93% (N = 902) of patients is ≥F2, 12% (N = 116) of patients were treatment experienced, 10% (N = 97) were OST patients (methadone and buprenorphine). 546 PWID achieved sustainable viral response at 12 weeks post-treatment (SVR 12w) point, including 4% (N = 22) drop-out cases. SVR 12w among PWID patients was achieved in 89% (N = 488). Genotypes distribution is 50% (N = 271) G1, 6% (N = 36) G2, 42% (N = 230) G3, 2% (N = 9) G4. 12-week treatment regimens were applied for 88% patients: SOF + RBV + Peg-IFN during 12 weeks was used in 82% (N = 448) of patients – SVR 12w was achieved in 92% (N = 410); and SOF + RBV during 12 weeks was used in 6% (N = 34) of patients – SVR 12w was achieved in 79% (N = 27). 10% (N = 56) of patients received SOF + RBV during 24 weeks, SVR 12w – 77% (N = 43). The rest 2% (N = 8) of patients received SOF in combination with daclatasvir with or without RBV, SVR 12w – 100% (N = 8). Conclusions: Short-term treatment regimens and multidisciplinary treatment approach within the CIM result in high level of adherence to HCV treatment and high cure rate among PWID patients. SAT-271 On-treatment HCV RNA monitoring is not a cost-effective means of identifying non-adherence and has no predictive value S. Demma1, W. Rosenberg1, D. Macdonald1. 1Institute of Liver and Digestive Health, University College London, London, United Kingdom E-mail: [email protected] Background and Aims: The high cost of directly-acting antiviral (DAA) treatment for HCV means local guidelines often mandate frequent HCV RNA testing on treatment to detect non-adherence or allow earlytermination of treatment in on-treatment relapse. It is unclear whether this monitoring is sensitive or cost-effective for this purpose. An HCV RNA increase of >1 log from an on-treatment nadir may indicate either non-adherence or viral breakthrough. We aimed to determine the frequency of this event in a retrospective cohort study of patients treated with DAA. We also examined whether slow responses
to treatment (HCV RNA quantifiable at week 2) were more common in patients with advanced disease and if this predicted relapse. Methods: We analysed viral loads, disease stage, HIV status, treatment experience, liver transplant status and outcome in 547 patients who underwent baseline and on-treatment testing on at least 3 occasions during treatment (total 3,957 HCV RNA tests) between May 2014 and June 2016 at the Royal Free London NHS Trust). Results: 4 patients had a viral load increase >1 log from an ontreatment nadir all of which occurred at week 8. One of these was suspected to be non-adherent and with close supervision achieved a full response at end of treatment and sustained virological response (SVR) at week 12. 3 had on-treatment relapses despite adequate adherence. Compared with a control group of non-cirrhotic patients, proportions of patients with a quantifiable HCV RNA at day 10–20 were greater in patients with decompensated (62% vs 47%, p = 0.0279 two-tailed χ2 test) and compensated cirrhosis (63% vs 47%, p = 0.002). HIV, transplant and treatment experience status had no significant impact on viral load at week 2 independently of disease stage. Across the whole cohort, post-treatment relapsers did not have a significantly higher proportion of quantifiable viral loads at any time point on treatment compared with those with an SVR 12 weeks after treatment. Conclusions: We estimate the cost of on-treatment viral load monitoring in this cohort to be €231,000. Only one patient was identified with poor adherence by this means. On-treatment relapses were all identified after dispensing their final 4 weeks of treatment. On-treatment HCV RNA monitoring is not a cost-effective or costsaving method of identifying non-adherence or on-treatment breakthrough respectively and has no predictive value with regard to treatment outcome. SAT-272 Characterization of novel GT-1b resistant-associated substitutions (RASs) selected by NS5A inhibitor-based regimens S. Fourati1,2, F. Donati1,2, A. Soulier1,2, C. Hézode3, L. Poiteau1,2, L. Ollier4, H. Danso1,2, A. Ahmed-Belkacem1,2, S. Chevaliez1,2, J.-M. Pawlotsky1,2. 1Virology, INSERM U955; 2Virology Department, National Reference Center for Viral Hepatitis B, C and D; 3Hepatology, INSERM U955, Créteil; 4Virology, Archet2 Hospital, Nice, France E-mail: [email protected] Background and Aims: Given the long-term persistence of HCV NS5A RASs, retreatment of patients failing NS5A inhibitor-based regimens is challenging. The incidence and nature of NS5A RASs have been well-characterized in clinical trials. However, resistance patterns in real-world patients can substantially differ. The French National Reference Center for Viral Hepatitis B, C and D performs HCV resistance testing in patients failing DAA-containing regimens across the country. NS5A substitutions at positions involved in resistance to NS5A inhibitors never described so far were detected and fully characterized. Methods: A total of 40 patients infected with HCV GT-1b failing an NS5A inhibitor-based regimen were included. NS5A sequences were assessed at baseline and at treatment failure by means of population sequencing. Nine known RAS positions located in domain I of NS5A were analyzed (residues 28, 29, 30, 31, 32, 58, 62, 92 and 93). Never reported AA substitutions at these positions were introduced into the Con-1 replicon to evaluate the susceptibility of the corresponding GT-1b NS5A variants to NS5A inhibitors. Results: Thus far unreported emerging substitutions in NS5A located at known RAS positions were identified in 2 patients. In patient 1, L28I co-emerged along with pre-existent R30S (and L31M) after the failure of 12 weeks of sofosbuvir (SOF) plus daclatasvir (DCV). In the replicon model, the combination of L28I and R30S conferred a 60-fold increase in DCV EC50, in the same order as the triple mutant L28I/R30S/L31M (45-fold). The replication capacities of these mutants were in the same order as that of WT virus (128% and 114%, respectively). In patient 2, the novel R30N substitution was detected along with the
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to treatment (HCV RNA quantifiable at week 2) were more common in patients with advanced disease and if this predicted relapse. Methods: We analysed viral loads, disease stage, HIV status, treatment experience, liver transplant status and outcome in 547 patients who underwent baseline and on-treatment testing on at least 3 occasions during treatment (total 3,957 HCV RNA tests) between May 2014 and June 2016 at the Royal Free London NHS Trust). Results: 4 patients had a viral load increase >1 log from an ontreatment nadir all of which occurred at week 8. One of these was suspected to be non-adherent and with close supervision achieved a full response at end of treatment and sustained virological response (SVR) at week 12. 3 had on-treatment relapses despite adequate adherence. Compared with a control group of non-cirrhotic patients, proportions of patients with a quantifiable HCV RNA at day 10–20 were greater in patients with decompensated (62% vs 47%, p = 0.0279 two-tailed χ2 test) and compensated cirrhosis (63% vs 47%, p = 0.002). HIV, transplant and treatment experience status had no significant impact on viral load at week 2 independently of disease stage. Across the whole cohort, post-treatment relapsers did not have a significantly higher proportion of quantifiable viral loads at any time point on treatment compared with those with an SVR 12 weeks after treatment. Conclusions: We estimate the cost of on-treatment viral load monitoring in this cohort to be €231,000. Only one patient was identified with poor adherence by this means. On-treatment relapses were all identified after dispensing their final 4 weeks of treatment. On-treatment HCV RNA monitoring is not a cost-effective or costsaving method of identifying non-adherence or on-treatment breakthrough respectively and has no predictive value with regard to treatment outcome. SAT-272 Characterization of novel GT-1b resistant-associated substitutions (RASs) selected by NS5A inhibitor-based regimens S. Fourati1,2, F. Donati1,2, A. Soulier1,2, C. Hézode3, L. Poiteau1,2, L. Ollier4, H. Danso1,2, A. Ahmed-Belkacem1,2, S. Chevaliez1,2, J.-M. Pawlotsky1,2. 1Virology, INSERM U955; 2Virology Department, National Reference Center for Viral Hepatitis B, C and D; 3Hepatology, INSERM U955, Créteil; 4Virology, Archet2 Hospital, Nice, France E-mail: [email protected] Background and Aims: Given the long-term persistence of HCV NS5A RASs, retreatment of patients failing NS5A inhibitor-based regimens is challenging. The incidence and nature of NS5A RASs have been well-characterized in clinical trials. However, resistance patterns in real-world patients can substantially differ. The French National Reference Center for Viral Hepatitis B, C and D performs HCV resistance testing in patients failing DAA-containing regimens across the country. NS5A substitutions at positions involved in resistance to NS5A inhibitors never described so far were detected and fully characterized. Methods: A total of 40 patients infected with HCV GT-1b failing an NS5A inhibitor-based regimen were included. NS5A sequences were assessed at baseline and at treatment failure by means of population sequencing. Nine known RAS positions located in domain I of NS5A were analyzed (residues 28, 29, 30, 31, 32, 58, 62, 92 and 93). Never reported AA substitutions at these positions were introduced into the Con-1 replicon to evaluate the susceptibility of the corresponding GT-1b NS5A variants to NS5A inhibitors. Results: Thus far unreported emerging substitutions in NS5A located at known RAS positions were identified in 2 patients. In patient 1, L28I co-emerged along with pre-existent R30S (and L31M) after the failure of 12 weeks of sofosbuvir (SOF) plus daclatasvir (DCV). In the replicon model, the combination of L28I and R30S conferred a 60-fold increase in DCV EC50, in the same order as the triple mutant L28I/R30S/L31M (45-fold). The replication capacities of these mutants were in the same order as that of WT virus (128% and 114%, respectively). In patient 2, the novel R30N substitution was detected along with the
Journal of Hepatology 2017 vol. 66 | S543–S750
S737