Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease.
BACKGROUND
Treatment of genotype 1 hepatitis C virus (HCV) infection with combination directly acting antivirals (DAA) for 8-24 weeks is associated with high rates of sustained virologic response (SVR). We previously demonstrated that adding a third DAA to ledipasvir and sofosbuvir (LDV/SOF) can result in high SVR rates in patients without cirrhosis. In this study, we investigated whether a similar regimen would yield equivalent rates of cure in patients with advanced liver fibrosis.


METHODS
Fifty patients were enrolled at the Clinical Research Center of the National Institutes of Health and associated healthcare centers. Enrollment and follow-up data from April 2014 to June 2015 are reported here. Eligible participants were aged ≥18 years, had chronic HCV genotype 1 infection (serum HCV RNA ≥2000 IU/mL), and stage 3-4 liver fibrosis. HCV RNA was measured using a reverse-transcription polymerase chain reaction assay.


RESULTS
Of patients treated with LDV, SOF, and the NS3/4A protease inhibitor GS-9451 for 6 weeks, 76% (38 of 50; 95% confidence interval, 60%-85%) had SVR achieved 12 weeks after the end of treatment. There was no statistically significant difference in treatment efficacy between treatment-naive patients (72%, 18 of 25) and those with treatment experience (80%; 20 of 25) (P = .51). Overall, 11 patients (22%) experienced virologic relapse, and 1 (2%) was lost to follow-up at 4 weeks after treatment. No serious adverse events, discontinuations, or deaths were associated with this regimen.


CONCLUSIONS
Adding a third DAA to LDV/SOF may result in a moderate SVR rate, lower than that observed in patients without cirrhosis. Significant liver fibrosis remains an impediment to achieving SVR with short-duration DAA therapy.
CT01805882.
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Sarah
S
Kattakuzhy
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Eleanor
E
Wilson
Critical Care Medicine Department, NIH Clinical Center.
Sreetha
S
Sidharthan
Critical Care Medicine Department, NIH Clinical Center.
Zayani
Z
Sims
Laboratory of Immunoregulation.
Mary
M
McLaughlin
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Angie
A
Price
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Rachel
R
Silk
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Chloe
C
Gross
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Elizabeth
E
Akoth
ParkerTide.
Maryellen
M
McManus
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Benjamin
B
Emmanuel
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Shikha
S
Shrivastava
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Lydia
L
Tang
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Amy
A
Nelson
Unity Health Care, Washington D.C.
Gebeyehu
G
Teferi
Unity Health Care, Washington D.C.
Jose
J
Chavez
Department of Hepatology, INOVA Fairfax Hospital, Virginia.
Brian
B
Lam
Gilead Sciences, Foster City, California.
Hongmei
H
Mo
Gilead Sciences, Foster City, California.
Anuoluwapo
A
Osinusi
Collaborative Clinical Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
Michael A
MA
Polis
Critical Care Medicine Department, NIH Clinical Center.
Henry
H
Masur
Department of Hepatology, St Josephs Hospital and Medical Center, Creighton University, Phoenix, Arizona.
Anita
A
Kohli
Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, Baltimore.
Shyamasundaran
S
Kottilil
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000008:administration & dosage*; D000069474:Sofosbuvir / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C573362:GS-9451; D011804:Quinolines; C586541:ledipasvir; D000069474:Sofosbuvir
advanced fibrosis; hepatitis C; short-duration