The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures
Abstract
:1. Introduction
2. Methods
2.1. Study Population
Ethics Statement
2.2. Inclusion and Exclusion Criteria
2.3. Analysis of RAS
3. Results
3.1. Baseline Characteristics
3.2. European Prevalence of RAS after DAA Failure
3.3. RAS in Unusual Subtypes Defined as GT1 Non-A/B, GT3 Non-A, and GT4 Non-A/D
3.4. RAS Specified over DAA Regimens
3.4.1. Asunaprevir + Daclatasvir (ASV + DAC)
3.4.2. First Generation Protease Inhibitors (Pis)
3.4.3. Grazoprevir + Elbasvir (GZR + ELB)
3.4.4. Ombitasvir + Paritaprevir + Ritonavir + Dasabuvir (OMB + PTV/r + DAS)
3.4.5. Simeprevir + Daclatasvir (SIM + DAC)
3.4.6. Sofosbuvir-Mono (SOF)
3.4.7. Sofosbuvir + Daclatasvir (SOF + DAC)
3.4.8. Sofosbuvir + Ledipasvir (SOF + LDV)
3.4.9. Sofosbuvir + Simeprevir (SOF + SIM)
3.4.10. Sofosbuvir + Velpatasvir (SOF + VEL)
3.4.11. Sofosbuvir + Velpatasvir + Voxilaprevir (SOF + VEL + VOX)
3.5. Multiclass RAS
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cohort | Failure (N = 938) | |
---|---|---|
Sex (n = 895) (%) | Male | 705 (79) |
Age in years (mean(IQR)) (n = 460) | Sample taken | 53.7 (48.3–59.7) |
Type of failure, n (%) | Breakthrough | 59 (6) |
Relapses | 435 (46) | |
Partial-responder | 21 (2) | |
Non-responder | 30 (3) | |
Unspecified | 393 (42) | |
Fibrosis stage, (n = 615) (%) | F0 | 19 (3) |
F1 | 61 (10) | |
F2 | 79 (13) | |
F3 | 89 (14) | |
F4 unspecified | 73 (12) | |
F4 compensated | 283 (45) | |
F4 decompensated | 11 (2) | |
Previous therapy, n (%) | No | 179 (19) |
Yes, not with DAAs | 218 (23) | |
Yes, with first generations protease inhibitors | 64 (7) | |
Unknown | 477 (51) | |
Country of submission (%) | Denmark | 14 (1) |
France | 2 (0.2) | |
Germany | 15 (2) | |
Italy | 225 (24) | |
Israel | 102 (11) | |
the Netherlands | 32 (3) | |
Romania | 20 (2) | |
Russia | 168 (18) | |
Spain | 351 (37) | |
Turkey | 9 (1) |
Id | Subtype | Bootstrap Support | Reference Sequence | Treatment at Failure | Ns3 Ras | Ns5a Ras | Ns5b Ras |
---|---|---|---|---|---|---|---|
HC_01 | 1l | 100 | KC248193 | SOF + DAC | No RAS | ||
HC_02 | 1l | 100 | KC248193 | SOF + LDV | R30Q | No RAS | |
HC_03 | 1g | 100 | 1Gen PI | Q41H | |||
HC_04 HC_05 | 3b 3b | 100 100 | D49374 D49374 | SOF + LDV SOF + DAC | Q168H | V31M | |
HC_06 | 4k | 100 | EU392173 | SOF + LDV | |||
HC_07 | 4n | 100 | FJ462441 | SOF + SIM + RBV | No RAS | No RAS | No RAS |
HC_08 | 4r | 100 | FJ462439 | SOF + LDV | L31M, N62S | ||
HC_09 | 4t | 100 | FJ839869 | SOF + LDV | L28M, P58H | No RAS | |
HC_10 | N.D * | 81/61/67 | H77 | SOF + LDV | No RAS | L31IM, H58P, E62AD | No RAS |
HC_11 | N.D ** | 100/98/52 | KJ439768 | GZR + ELB | No RAS | R30S, M31V, Y93S | |
HC_12 | 1b *** | SOF + VEL | No RAS | No RAS | |||
HC_13 | 1b *** | SOF + RBV | No RAS |
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Popping, S.; Cento, V.; Seguin-Devaux, C.; Boucher, C.A.B.; de Salazar, A.; Heger, E.; Mor, O.; Sayan, M.; Salmon-Ceron, D.; Weis, N.; et al. The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures. Viruses 2022, 14, 16. https://doi.org/10.3390/v14010016
Popping S, Cento V, Seguin-Devaux C, Boucher CAB, de Salazar A, Heger E, Mor O, Sayan M, Salmon-Ceron D, Weis N, et al. The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures. Viruses. 2022; 14(1):16. https://doi.org/10.3390/v14010016
Chicago/Turabian StylePopping, Stephanie, Valeria Cento, Carole Seguin-Devaux, Charles A. B. Boucher, Adolfo de Salazar, Eva Heger, Orna Mor, Murat Sayan, Dominique Salmon-Ceron, Nina Weis, and et al. 2022. "The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures" Viruses 14, no. 1: 16. https://doi.org/10.3390/v14010016
APA StylePopping, S., Cento, V., Seguin-Devaux, C., Boucher, C. A. B., de Salazar, A., Heger, E., Mor, O., Sayan, M., Salmon-Ceron, D., Weis, N., Krarup, H. B., de Knegt, R. J., Săndulescu, O., Chulanov, V., van de Vijver, D. A. M. C., García, F., & Ceccherini-Silberstein, F., on behalf of the HepCare as Part of the European Society for Translational Antiviral Research (ESAR). (2022). The European Prevalence of Resistance Associated Substitutions among Direct Acting Antiviral Failures. Viruses, 14(1), 16. https://doi.org/10.3390/v14010016