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Gastroenterology. 2016 Dec;151(6):1131-1140.e5. doi: 10.1053/j.gastro.2016.08.004. Epub 2016 Aug 24.

Effectiveness of Ledipasvir-Sofosbuvir Combination in Patients With Hepatitis C Virus Infection and Factors Associated With Sustained Virologic Response.

Author information

1
Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, California. Electronic address: norah.terrault@ucsf.edu.
2
Goethe University Hospital, Frankfurt, Germany.
3
Department of Medicine, Saint Louis University School of Medicine, St Louis, Missouri.
4
Yale University School of Medicine, New Haven, Connecticut.
5
Liver Disease Center, Scripps Clinic, La Jolla, California.
6
Liver Wellness Center, Little Rock, Arkansas.
7
University of California San Diego, San Diego, California.
8
University of Michigan Health System, Ann Arbor, Michigan.
9
Liver Institute of Virginia, Richmond, Virginia.
10
Sheba Medical Center, Ramat Gan, Israel.
11
University of North Carolina, Chapel Hill, North Carolina.
12
Johns Hopkins, Baltimore, Maryland.
13
University of Florida, Gainesville, Florida.

Abstract

BACKGROUND & AIMS:

The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure.

METHODS:

We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12.

RESULTS:

The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (≥3.5 g/dL), lower total bilirubin (≤1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use.

CONCLUSIONS:

Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

KEYWORDS:

Antiviral; DAA; NS5A Inhibitor; NS5B Inhibitor

PMID:
27565882
PMCID:
PMC5300778
DOI:
10.1053/j.gastro.2016.08.004
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

These authors disclose the following: Norah A. Terrault discloses institutional grant funding from Gilead, AbbVie, Merck, BMS, and Biotest and has served as consultant for Merck, Achillion, Bristol-Myers Squibb, and Janssen. Stefan Zeuzem discloses consulting and sponsored lectures from AbbVie, BMS, Gilead, Janssen, and Merck. Mark S. Sulkowski discloses grants paid to his institution from AbbVie, BMS, Gilead, Janssen, and Merck and consulting from Achillion, AbbVie, BMS, Gilead, Janssen, and Merck. Paul J. Pockros discloses grant funding from Gilead, BMS, AbbVie, Merck, Janssen, consulting from Gilead, BMS, AbbVie, Merck, and Janssen and sponsored lectures from Gilead, BMS, AbbVie, and Janssen. Anna S. Lok discloses grant funding from AbbVie, Idenix, BMS, Gilead, and Merck and consulting for Gilead and Merck. Joseph K. Lim discloses grants paid to his institution from BMS, Gilead, Janssen, Hologic, and Merck and consulting for BMS, Gilead, Janssen, and Merck. Alexander Kuo discloses grant funding from Gilead. Mitchell L. Shiffman discloses grant funding from Genentech/Roche, Merck, Vertex, Janssen, Gilead, Bristol Myers Squibb, AbbVie, Glaxo and consulting from Genentech/Roche, Tibotec/Janssen, Vertex, Merck, Glaxo, Novartis, AbbVie, Gilead, and Bristol Myers Squibb. Adrian M. Di Bisceglie discloses grant funding and consulting from Gilead, AbbVie, BM. Michael W. Fried discloses grant funding and consulting from Merck, Janssen, Gilead, Bristol Myers Squibb, and AbbVie. David R. Nelson discloses grant funding from AbbVie, Gilead, BMS, Janssen, Merck, GSK. The remaining authors disclose no conflicts.

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