Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection.
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. 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. 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. 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. No patient in either 12-week group discontinued ledipasvir-sofosbuvir owing to an adverse event. 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. (Funded by Gilead Sciences; ION-1 ClinicalTrials.gov number NCT01701401.).
The authors' affiliations are listed in the Appendix.
Nezam
N
Afdhal
Stefan
S
Zeuzem
Paul
P
Kwo
Mario
M
Chojkier
Norman
N
Gitlin
Massimo
M
Puoti
Manuel
M
Romero-Gomez
Jean-Pierre
JP
Zarski
Kosh
K
Agarwal
Peter
P
Buggisch
Graham R
GR
Foster
Norbert
N
Bräu
Maria
M
Buti
Ira M
IM
Jacobson
G Mani
GM
Subramanian
Xiao
X
Ding
Hongmei
H
Mo
Jenny C
JC
Yang
Phillip S
PS
Pang
William T
WT
Symonds
John G
JG
McHutchison
Andrew J
AJ
Muir
Alessandra
A
Mangia
Patrick
P
Marcellin
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D005449:Fluorenes / Q000009:adverse effects / Q000627:therapeutic use*; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use; D000069474:Sofosbuvir; D014542:Uridine Monophosphate / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; D012367:RNA, Viral; C586541:ledipasvir; D012254:Ribavirin; D014542:Uridine Monophosphate; D000069474:Sofosbuvir