ABBV abstract re VL and outcomes - has implications for criteria used to determine GILD 8 week eligibility and also should provide good ammunition against MRK if they get approved
IMPLICATIONS OF BASELINE HCV RNA LEVEL AND INTRAPATIENT VIRAL LOAD VARIABILITY ON OBV/PTV/R + DSV 12-WEEK TREATMENT OUTCOMES
Introduction: High levels of pre-treatment HCV RNA may impact the risk of virologic relapse post-treatment. Within the ombitasvir/paritaprevir*/ritonavir and dasabuvir (3D) development program, we examined the effect of viral load on the risk of virologic relapse within various HCV RNA strata.
Material and Methods: Non-cirrhotic treatment-naïve HCV-infected patients who received 12 weeks of 3D (GT1b) or 3D+RBV (GT1a) were included in the analysis. Post-treatment relapse rates were summarized by pre-treatment HCV RNA thresholds. Intrapatient HCV RNA measurement variability was assessed by evaluating differences in HCV RNA levels between screening and baseline (median interval=3 weeks). Plasma samples were analyzed at a central laboratory using the Roche COBAS® TaqMan® RT-PCR assay v2.0.
Results: Among 618 patients, median baseline HCV RNA was 6.56 log10 IU/mL (3.6 million [M] IU/mL); 7/618 (1.1%) had post-treatment relapse. There was no association between baseline HCV RNA and relapse rate for any threshold (Table), with relapse rates of 1.2% and 0.9% below and above baseline HCV RNA of 10 million IU/mL, respectively. In patients who achieved SVR12 or relapsed, the median baseline HCV RNA was 6.55 and 6.66 log10 IU/mL, respectively (p=0.2). No relapses were observed for any patient with viral load <2.5M IU/mL. Intrapatient variability in HCV RNA measurements increased with rising baseline viremia. Screening and baseline HCV RNA measurements differed by >1M IU/mL in 55%, by >2M IU/mL in 35%, and by >3M IU/mL in 26% of patients. In the subset of patients with a screening HCV RNA above 2M IU/mL, 79% differed by >1M IU/mL, 53% differed by >2M IU/mL, and 40% differed by >3M IU/mL. At the 6M IU/mL threshold, 18% of patients had discordant baseline and screening HCV RNA values.
Conclusions: With this multi-targeted regimen, we did not identify any viral threshold for risk of relapse, suggesting that 12 weeks of therapy is optimal for minimizing the risk of relapse in naïve, non-cirrhotic patients, regardless of underlying host or viral factors. Intrapatient variability in HCV RNA measurements was common, suggesting that a subset of patients may be misclassified if viral thresholds are important for clinical decision-making.
*Paritaprevir was identified by AbbVie and Enanta.
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