Real-world Effectiveness for 12 Weeks of Ledipasvir–Sofosbuvir for Genotype 1 Hepatitis C

The Trio Health Study

E. B. Tapper; B. R. Bacon; M. P. Curry; D. T. Dieterich; S. L. Flamm; L. E. Guest; K. V. Kowdley; Y. Lee; N. C. Tsai; Z. M. Younossi; N. H. Afdhal


J Viral Hepat. 2017;24(1):22-27. 

In This Article

Abstract and Introduction


Early data regarding the "real-world" experience with novel therapies for hepatitis C (HCV) are encouraging. Data are still limited, however, regarding real-world rates of sustained virologic response (SVR) for ledipasvir–sofosbuvir (LDV-SOF), particularly for patients with prior treatment failure. We performed a retrospective cohort study of 1597 patients with chronic genotype 1 HCV who were treated using 12 weeks of the following regimens LDV-SOF±ribavirin (RBV) (n=1521 without RBV, n=76 with RBV). The primary outcome was SVR-determined at 12 weeks in an intention-to-treat design. Prescription according to Food and Drug Administration (FDA) approved labelling (adding RBV for patients with cirrhosis and treatment failure) was assessed in multivariate models. The study population was aged 60 years on average (range 19–89), 60% male, 50% Caucasian, 43% cared for at an academic centre and 30% cirrhotic. Overall, LDV-SOF resulted in a 94% SVR rate. Only 44 (2.9%) patients relapsed. LDV-SOF+RBV yielded SVR in 97% with 0 viral relapses. While cirrhosis and thrombocytopenia were associated with lower odds of SVR, in a multivariable regression model, only treatment at an academic centre and prescriptions contrary to FDA labelling were significantly associated with lower SVR—odds ratios, 0.56 95% CI (0.35–0.87) and 0.29 95% CI(0.12–0.68), respectively. The real-world experience with LDV-SOF mirrors the SVR rates observed in clinical trials. Efforts to promote prescription within FDA recommendations are warranted.


Well-tolerated and highly efficacious direct-acting antiviral therapies have transformed the care of patients with hepatitis C (HCV).[1–6] The patient experience of anti-HCV therapy has evolved from frequent treatment failures and adverse events to readily available cures without side effects.[7,8] Importantly though, these data in support of direct-acting antivirals (DAAs) come predominantly from industry sponsored registration trials. Prior advances in the context of clinical trials such as the first-generation DAAs—boceprevir and telaprevir—were met with disappointing results when applied in "real-world" settings.[9,10] The difficulty in translating trial experiences to the real-world led Kanwal and El Serag to describe an "unyielding" chasm between efficacy and effectiveness.[11]

There is reason to believe that the experience of the present generation of DAAs will prove different than the last. Early data regarding the "real-world" experience with novel DAAs are encouraging.[12–14] Unfortunately, data are still limited regarding real-world SVR rates for LDV-SOF, the most frequently prescribed regimen. A recent study by Backus et al. demonstrated SVR rates of 93%-96% after 8–12 weeks of LDV-SOF in 4365 treatment-naïve patients from the Veterans Administration,[15] effectively recapitulating the results of the ION-1 trial.[2] Data are lacking, however, regarding treatment-experienced patients.

Herein, we present data from 1597 patients with chronic genotype 1 HCV who were treated with 12 weeks of LDV-SOF with or without prior treatment failure.