Retreatment of patients with chronic hepatitis C who failed interferon-free direct acting antiviral therapy

Background:

Only few chronic hepatitis C patients treated with interferon-free DAA combinations fail to clear the virus. So far, little is known about how to best retreat these patients. In this study we summarize our “real world” experience of retreatment.

Methods:

Eighty three of 122 HCV monoinfected patients who failed IFN-free DAA therapy (GT1: 58, GT2: 1, GT3: 22, GT4: 2; IFN-therapy experienced: 51; cirrhosis: 52) were retreated and completed follow-up. For retreatment patients received a different DAA-combination than the one to which they failed. The drugs were prescribed according to availability and funding: ombitasvir/paritaprevir/dasabuvir (3D)± RBV: 20; ombitasvir/paritaprevir (2D): 1; SOF/daclatasvir (DCV)± RBV: 10; SOF/Ledipasvir (LDV)± RBV: 21; SOF/velpatasvir (VEL): 15; SOF/simeprevir (SMV): 4; elbasvir/grazoprevir (EBV/GZV): 3; SOF/VEL/voxelaprevir (VOX): 1; SOF/3D: 2; SOF/EBV/GZV: 5; PEG/SOF/RBV: 1. Treatment duration (12 or 24 weeks) and addition of RBV were at the discretion of the treating physician.

Results:

Out of the 83 patients who completed a retreatment 64 (77.1%) achieved SVR and 19 relapsed (GT1a: 8, GT1b: 4, GT3a: 6; GT4: 1; cirrhosis: 12; RAS in 12/14; after 3D ± RBV: 4; SOF/DCV ± RBV: 4; SOF/LDV ± RBV: 5; SOF/VEL: 2; SOF/SMV: 2; EBV/GZP: 1; SOF/RBV/peginterferon: 1). In two nonresponders to the first DAA-therapy retesting of the genotype revealed a different genotype: GT3a instead of GT1a and a yet unclassified subtype close to 1c instead of GT1b. Before the retreatment 38 of 50 tested patients had resistance-associated substitutions (RAS): 46% had isolated RAS, 24% had resistance to two and 3 to all three classes. Neither sex, cirrhosis, genotype nor RAS were significantly associated with failure after retreatment.

Ten of the 19 relapsers have finished a 2^nd retreatment; 3 of them relapsed again (SOF/VEL/RBV: GT3a; SOF/LDV/RBV: GT1a; EBV/GZV/SOF/RBV: GT1b; cirrhosis: 2). One (GT1a, cirrhosis) achieved SVR12 after the 3^rd retherapy with 24 weeks of 3D/SOF/RBV, and one (GT3a cirrhosis) achieved SVR4 after 24 weeks of glecaprevir/pibrentasvir, but died shortly thereafter.

Overall, 73 (87.9%) of the 83 patients achieved SVR.

Conclusions:

Most DAA failures retreated with a different regimen achieved SVR, however, a few patients required multiple retreatments.