Effectiveness of Sofosbuvir, Ledipasvir/Sofosbuvir, or Paritaprevir/Ritonavir/Ombitasvir and Dasabuvir Regimens for Treatment of Patients With Hepatitis C in the Veterans Affairs National Health Care…

George N. Ioannou, Lauren A. Beste, Michael F. Chang, Pamela K. Green, Elliott Lowy, Judith I. Tsui, Feng Su, Kristin Berry

We investigated the real-world effectiveness of sofosbuvir, ledipasvir/sofosbuvir, and paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD) in treatment of different subgroups of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, or 4. We performed a retrospective analysis of data from 17,487 patients with HCV infection (13,974 with HCV genotype 1; 2131 with genotype 2; 1237 with genotype 3; and 135 with genotype 4) who began treatment with sofosbuvir (n=2986), ledipasvir/sofosbuvir (n=11,327), or PrOD (n=3174), with or without ribavirin, from January 1, 2014 through June 20, 2015 in the Veterans Affairs healthcare system. Data through April 15, 2016 were analyzed to assess completion of treatments and sustained virologic response 12 weeks after treatment (SVR12). The mean age of patients was 61±7 years, 97% were male, 52% were non-Hispanic white, 29% were non-Hispanic black, 32% had a diagnosis of cirrhosis (9.9% with decompensated cirrhosis), 36% had a FIB-4 score >3.25 (indicator of cirrhosis), and 29% had received prior treatment. An SVR12 was achieved by 92.8% (95% CI, 92.3%-93.2%) of subjects with HCV genotype 1 infection (no significant difference between ledipasvir/sofosbuvir and PrOD regimens), 86.2% (95% CI, 84.6%-87.7%) of those with genotype 2 infection (treated with sofosbuvir and ribavirin), 74.8% (95% CI, 72.2%-77.3%) of those with genotype 3 infection (77.9% in patients given ledipasvir/sofosbuvir plus ribavirin, 87.0% in patients given sofosbuvir and pegylated-interferon plus ribavirin, and 70.6% of patients given sofosbuvir), and 89.6% (95% CI 82.8%-93.9%) of those with genotype 4 infection. Among patients with cirrhosis, 90.6% of patients with HCV genotype 1, 77.3% with HCV genotype 2, 65.7% with HCV genotype 3, and 83.9% with HCV genotype 4 achieved an SVR12. Among previously treated patients, 92.6% with genotype 1, 80.2% with genotype 2, 69.2% with genotype 3, and 93.5% with genotype 4 achieved an SVR12. Among treatment-experienced patients, 92.8% with genotype 1, 88.0% with genotype 2, 77.5% with genotype 3, and 88.3% with genotype 4 achieved an SVR12. Eight-week regimens of ledipasvir/sofosbuvir produced an SVR12 in 94.3% of eligible patients with HCV genotype 1 infection; this regimen was underused. High proportions of patients with HCV infections genotypes 1-4 (ranging from 75%-93%) in the VA national healthcare system achieved SVR12, approaching the results reported in clinical trials-especially patients with genotype 1 infection. An 8 week regimen of ledipasvir/sofosbuvir is effective for eligible patients with HCV genotype 1 infection and could produce cost savings. There is substantial room for improvement in SVRs among persons with cirrhosis and genotype 2 or 3 infections.