Real-world effectiveness data are needed to inform hepatitis C virus (HCV) treatment decisions. The uptake of ledipasvir/sofosbuvir (LDV/SOF) regimens across health care settings has been rapid, but variations often occur in clinical practice. The aim of this study was to assess sustained virologic response (SVR) of LDV/SOF6ribavirin (RBV) in routine medical practice. This observational, intent-to-treat cohort was comprised of 4,365 genotype 1, treatment-naive, HCV-infected veterans treated with LDV/SOF6RBV. SVR rates were 91.3% (3,191/3,495) for LDV/SOF and 92.0% (527/573) for LDV/SOF1RBV (P 5 0.65). African American race (odds ratio 0.70, 95% confidence interval 0.54-0.90, P 5 0.004) and FIB-4 >3.25 (odds ratio 0.56, 95% confidence interval 0.43-0.71, P < 0.001) were independently associated with decreased likelihood of SVR; age, sex, body mass index, decompensated liver disease, diabetes, genotype 1 subtype, and regimen did not predict SVR. In models limited to those who completed 12 weeks of treatment, African American race was no longer a significant predictor of SVR but FIB-4 >3.25 (odds ratio 0.35, 95% confidence interval 0.24-0.50, P < 0.001) remained. Among those without cirrhosis (defined by FIB-4 3.25) and with baseline HCV RNA<6,000,000 IU/mL, SVR rates were 93.2% (1,020/1,094) for those who completed 8 weeks of therapy and 96.6% (875/906) for those who completed 12 weeks of therapy (P 5 0.001). Conclusions: In this real-world cohort, SVR rates with LDV/SOF6RBV nearly matched the rates reported in clinical trials and were consistently high across all subgroups; those without cirrhosis but with HCV RNA<6,000,000 IU/mL were less likely to achieve SVR with 8 weeks compared to 12 weeks of therapy, although the numeric difference in SVR rates was small. (HEPATOLOGY 2016;64:405-414)

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Summary Background Real‐world effectiveness data are needed to inform hepatitis C virus (HCV) treatment decisions. Aim To assess sustained virological response (SVR) of sofosbuvir (SOF)‐based regimens in routine medical practice. Methods Observational, intent‐to‐treat cohort analysis of genotype 1 and 2 HCV‐infected veterans initiating SOF‐based regimens with recommended treatment duration of 12 weeks. Results Four thousand and twenty‐six veterans with genotype 1 (N = 3203) and genotype 2 (N = 823) comprise the cohort. SVR rates for genotype 1 were 66.8% for SOF + peginterferon + ribavirin (RBV), 75.3% for SOF + simeprevir (SIM), 74.1% for SOF + SIM + RBV and for genotype 2 were 79.0% for SOF + RBV. Genotype 1 patients were less likely to achieve SVR with BMI ≥30 (OR 0.64, 95% CI 0.49–0.84, P < 0.001), a history of decompensated liver disease (OR 0.51, 95% CI 0.36–0.71, P < 0.001), treatment experience (OR 0.58, 95% CI 0.48–0.71, P < 0.001), APRI >2 (OR 0.44, 95% CI 0.36–0.55, P < 0.001) and with SOF + PEG + RBV compared with SOF + SIM (OR 0.50, 95% CI 0.40–0.62, P < 0.001). Age, sex, race/ethnicity, diabetes and genotype subtype did not predict SVR. Odds of achieving SVR with SOF + SIM + RBV did not differ compared with SOF + SIM (OR 1.03, 95% CI 0.75–1.44, P = 0.86). Genotype 2 patients were less likely to achieve SVR with prior treatment experience (OR 0.55, 95% CI 0.35–0.88, P = 0.009) and APRI >2 (OR 0.39, 95% CI 0.25–0.62, P < 0.001). Conclusions In this real‐world cohort, SVR rates were lower than in clinical trials. Genotype 1 and 2 HCV‐infected patients with advanced liver disease by APRI >2 or FIB‐4 > 3.25 were significantly less likely to achieve SVR. For genotype 1, a SOF + SIM ± RBV regimen was associated with a higher likelihood of SVR.

The Department of Veterans Affairs (VA) has a system-wide, patient-centric electronic medical record system (EMR) within which the authors developed the Clinical Case Registries (CCR) to support population-centric delivery and evaluation of VA medical care. To date, the authors have applied the CCR to populations with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Local components use diagnosis codes and laboratory test results to identify patients who may have HIV or HCV and support queries on local care delivery with customizable reports. For each patient in a local registry, key EMR data are transferred via HL7 messaging to a single national registry. From 128 local registry systems, over 60,000 and 320,000 veterans in VA care have been identified as having HIV and HCV, respectively, and entered in the national database. Local and national reports covering demographics, resource usage, quality of care metrics and medication safety issues have been generated.

In this robust real-world cohort, SVR rates were similar to clinical trials. FIB-4 > 3.25 and high BMI were significant negative predictors of SVR. Reduced odds of SVR in African Americans and with OPrD + RBV likely arose from excess early discontinuation as these factors were no longer significant, when limited to patients completing a 12-week course.