Clinical value of on-treatment HCV RNA levels during different approved sofosbuvir-based antiviral regimens.

EASL guidelines recommend HCV-RNA measurements at specific time-points during sofosbuvir(SOF)-therapy. However, it remains unclear, how these results should be interpreted. We aimed to analyse whether on-treatment HCV-RNA levels predict relapse comparing the CobasAmpliPrep/CobasTaqMan v2.0 (CAP/CTM) and Abbott RealTime HCV (ART) assays.Samples were collected from 298 patients(HCV-genotypes; GT1-5) at weeks(w) 0, 1, 2, 4, 8, 12, 16, 20 and 24 during SOF-based therapy at two University clinics and tested for HCV-RNA level by CAP/CTM and ART. Patients were treated with SOF/ribavirin(RBV) 12/24w (n=99), pegylated-interferon-alfa(Peg-IFN)/SOF/RBV 12w (n=51), SOF/simeprevir(SMV)±RBV 12w (n=69) or SOF/daclatasvir±RBV 12/24w (n=79).HCV-RNA levels during the first 4 weeks of SOF/RBV-therapy were significantly lower in GT3-patients who achieved SVR compared with those who relapsed. All GT3-patients with a week 2 result <45IU/ml by CAP/CTM achieved SVR but only 33% of those with ⩾45IU/ml(p=0.0003). Similar results were documented with ART and 60IU/ml as cut-off (SVR:100% vs. 29%;p=0.0002). In contrast, HCV-RNA levels during early treatment phases were not significantly related to relapse in patients treated with other SOF-based regimens. Residual HCV-RNA was frequently detected by ART at later stages of therapy. However, SVR-rates remained high in these patients. At the end of SOF/SMV±RBV-therapy HCV-RNA was detectable with ART in 20% of patients, of whom 92% achieved SVR.HCV-RNA levels assessed at week 2 of SOF/RBV-therapy can predict relapse in GT3-patients. Detectable HCV-RNA results at later stages during SOF-based therapy may occur frequently with the more sensitive ART. However, this should not lead to treatment extension.