Real‐world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment‐naive, genotype 1 hepatitis C‐infected patients

Abstract

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)

Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1–Coinfected Patients Treated in Routine Practice

“…More recently, in an integrated analysis of all phase III LDV/SOF studies, African American race was associated with decreased SVR rates in those receiving 8-week regimens of LDV/SOF [11]. A VA real-world cohort that included HCV monoinfected and HIV/HCV coinfected patients showed similar results in African Americans [12]. In a HIV/HCV co-infection clinical trial, Naggie and colleagues found that, when compared to non-black patients, black patients had lower SVR12 rates, 90% vs 99% p<0.001, respectively, and higher relapse rates [5].…”

“…In the DAA era, African American race has been associated with lower SVR rates including those receiving 8 week LDV/SOF regimens [11][12] and in one 12-week clinical trial of HIV/HCV coinfection, both in genotype 1 (GT1) infections [5]. In ION-4, a study of LDV/SOF in HIV/HCV coinfection, the overall SVR rate was 96% but was only 90% in AfricanAmericans, reflecting all 10 relapses in the study, eight of whom received efavirenz-containing regimens [5].…”

Sofosbuvir‐based regimens for the treatment of chronic hepatitis C in severe renal dysfunction

“…Safety and efficacy of SOF‐containing HCV regimens have been formally evaluated in over 10,000 patients in registration studies5, 6 and real‐world cohorts 7, 8, 9. Overall, the use of SOF appears safe with few significant toxicities reported.…”

C-WORTHY: the beginning of the rise of elbasvir and grazoprevir for the treatment of hepatitis C genotype 1 mono and HIV co-infected patients

“…Since the release of the first generation DAA's in 2011 there has been an explosion in the number and combination of DAA's available. Clinical trials have consistently reported SVR 12 rates >95% for most patient populations, including those patients co-infected with HIV, which have been supported by recent real world data (12)(13)(14). Treatment guidelines maintained as a living document online by the collaboration of American Association for the Study of Liver Disease (AASLD) and the Infectious Diseases Society of America (IDSA) are rapidly changing, however all oral DAA therapy is now the standard of care for all patient populations (15).…”