24725239
BACKGROUND	In phase 2 studies , treatment with the all-oral combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor ledipasvir resulted in high rates of sustained virologic response among previously untreated patients with hepatitis C virus ( HCV ) genotype 1 infection .
METHODS	We conducted a phase 3 , open-label study involving previously untreated patients with chronic HCV genotype 1 infection .
METHODS	Patients were randomly assigned in a 1:1:1:1 ratio to receive ledipasvir and sofosbuvir in a fixed-dose combination tablet once daily for 12 weeks , ledipasvir-sofosbuvir plus ribavirin for 12 weeks , ledipasvir-sofosbuvir for 24 weeks , or ledipasvir-sofosbuvir plus ribavirin for 24 weeks .
METHODS	The primary end point was a sustained virologic response at 12 weeks after the end of therapy .
RESULTS	Of the 865 patients who underwent randomization and were treated , 16 % had cirrhosis , 12 % were black , and 67 % had HCV genotype 1a infection .
RESULTS	The rates of sustained virologic response were 99 % ( 95 % confidence interval [ CI ] , 96 to 100 ) in the group that received 12 weeks of ledipasvir-sofosbuvir ; 97 % ( 95 % CI , 94 to 99 ) in the group that received 12 weeks of ledipasvir-sofosbuvir plus ribavirin ; 98 % ( 95 % CI , 95 to 99 ) in the group that received 24 weeks of ledipasvir-sofosbuvir ; and 99 % ( 95 % CI , 97 to 100 ) in the group that received 24 weeks of ledipasvir-sofosbuvir plus ribavirin .
RESULTS	No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event .
RESULTS	The most common adverse events were fatigue , headache , insomnia , and nausea .
CONCLUSIONS	Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection .
CONCLUSIONS	( Funded by Gilead Sciences ; ION-1 ClinicalTrials.gov number NCT01701401 . )

