Comparative analysis of direct-acting antiviral regimens across Hepatitis C genotypes and clinical characteristics among patients under routine clinical care in the US.

Document Type

Conference Proceeding

Publication Date

2018

Publication Title

Hepatol

Abstract

Background: We used data from the Chronic Hepatitis Cohort study (CHeCS) to compare the efficacy of direct acting antiviral (DAA) regimens among “real world” patients whose clinical status, hepatitis C virus (HCV) genotype (GT), and treatment history may vary from those of previous reports. Methods: Multivariate analysis of achieving sustained virologic response (SVR) among 3612 HCV patients who received at least 12 weeks of treatment with one of eight DAA regimens through 2017: Generation 1: sofosbuvir (SOF) with ribavirin (RBV); Generation 2, with and without RBV: daclatasvir +SOF, grezoprevir +elbasvir, paritoprevir +ritonavir +ombitasvir (with and without dasabuvir), simeprevir +SOF, and SOF +ledipasvir; and Generation 3, with and without RBV: SOF +velpatasavir. Propensity scores were used to adjust for adjuvant RBV treatment selection-bias. Results: The overall observed SVR rate for 12-week regimens was 95%. However, odds of achieving SVR varied significantly by sex (adjusted odds ratio [aOR] for male vs female patients=0.70, 95%CI 0.56-0.87); use of proton pump inhibitors (aOR=0.72, 95%CI 0.56-0.93); diabetes (aOR=0.42, 95%CI 0.34-0.52); and cirrhosis status (aOR=0.35, 95%CI 0.25-0.49 and 0.73, 95%CI 0.59-0.91 for decompensated and compensated cirrhosis, respectively, compared to no cirrhosis). Patients with GT3 had significantly lower odds of SVR than those with GT1 (aOR=0.27, 95%CI 0.15-0.52) and GT2 (aOR=0.09, 95%CI 0.05-0.19). Previous DAA treatment failure reduced odds of SVR (aOR=0.13, 95%CI 0.08-0.20). Each one month increment of DAA treatment increased odds of SVR by 90% (aOR=1.94, 95%CI 1.73-2.16). With adjuvant RBV, each subsequent generation demonstrated better efficacy (Gen1 vs 2: aOR=0.32, 95%CI 0.21-0.47; Gen1 vs 3: aOR=0.03, 95%CI 0.01-0.11; Gen2 vs 3: aOR=0.10, 95%CI 0.03-0.32), but there was no difference between Gen2 and Gen3 in the absence of RBV (aOR=1.11, 95%CI 0.67-1.83). Use of RBV doubled the odds of SVR among patients with decompensated cirrhosis (aOR=2.08, 95%CI 1.13-3.85). Conclusion: Despite high rates of successful treatment response, patients who failed prior DAA treatment, and those with cirrhosis or decompensated cirrhosis, remain at increased risk of treatment failure. Increased treatment duration (among all patients) and the use of RBV (among patients with decompensated cirrhosis) independently improved the odds of SVR. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Volume

68

First Page

897A

Last Page

898A

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