1From the Digestive Disease Institute, Virginia Mason Medical Center, Seattle (K.V.K.); Henry Ford Health Systems, Detroit (S.C.G.); University of Pennsylvania, Philadelphia (K.R.R.); University of California Davis Medical Center, Sacramento (L.R.), University of California at San Diego Medical Center, San Diego (M.C.), Scripps Clinic, La Jolla (P.J.P.), and Gilead Sciences, Foster City (G.M.S., D.A., E.S., R.H.H., P.S.P., W.T.S., J.G.M.) - all in California; Hofstra North Shore-Long Island Jewish School of Medicine, Manhasset, NY (D.E.B.); Texas Liver Institute and University of Texas Health Science Center, San Antonio (E.L.), and Texas Clinical Research Institute, Arlington (R.G.) - both in Texas; Liver Institute of Virginia, Bon Secours Health System, Richmond and Newport News (M.L.S.), Digestive and Liver Disease Specialists, Norfolk (M.R.), and Metropolitan Liver Diseases, Fairfax (V.R.) - all in Virginia; Center for Liver Diseases, School of Medicine, University of Miami, Miami (E.S.); Quality Medical Research, Nashville (R.H.); Saint Louis University, St. Louis (A.M.D.); Duke University Medical Center, Durham (A.J.M.), and University of North Carolina, Chapel Hill (M.W.F.) - both in North Carolina; and Indianapolis Gastroenterology Research Foundation, Indianapolis (D.P.).
Background: High rates of sustained virologic response were observed among patients with hepatitis C virus (HCV) infection who received 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor ledipasvir. This study examined 8 weeks of treatment with this regimen.
Methods: In this phase 3, open-label study, we randomly assigned 647 previously untreated patients with HCV genotype 1 infection without cirrhosis to receive ledipasvir and sofosbuvir (ledipasvir-sofosbuvir) for 8 weeks, ledipasvir-sofosbuvir plus ribavirin for 8 weeks, or ledipasvir-sofosbuvir for 12 weeks. The primary end point was sustained virologic response at 12 weeks after the end of therapy.
Results: The rate of sustained virologic response was 94% (95% confidence interval [CI], 90 to 97) with 8 weeks of ledipasvir-sofosbuvir, 93% (95% CI, 89 to 96) with 8 weeks of ledipasvir-sofosbuvir plus ribavirin, and 95% (95% CI, 92 to 98) with 12 weeks of ledipasvir-sofosbuvir. As compared with the rate of sustained virologic response in the group that received 8 weeks of ledipasvir-sofosbuvir, the rate in the 12-week group was 1 percentage point higher (97.5% CI, -4 to 6) and the rate in the group that received 8 weeks of ledipasvir-sofosbuvir with ribavirin was 1 percentage point lower (95% CI, -6 to 4); these results indicated noninferiority of the 8-week ledipasvir-sofosbuvir regimen, on the basis of a noninferiority margin of 12 percentage points. Adverse events were more common in the group that received ribavirin than in the other two groups. No patient who received 8 weeks of only ledipasvir-sofosbuvir discontinued treatment owing to adverse events.
Conclusions: Ledipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis. No additional benefit was associated with the inclusion of ribavirin in the regimen or with extension of the duration of treatment to 12 weeks. (Funded by Gilead Sciences; ION-3 ClinicalTrials.gov number, NCT01851330 .).