• DOI:10.7326/M15-0642
• Corpus ID: 207538390

Four-Week Direct-Acting Antiviral Regimens in Noncirrhotic Patients With Hepatitis C Virus Genotype 1 Infection: An Open-Label, Nonrandomized Trial.

@article{Kohli2015FourWeekDA,
  title={Four-Week Direct-Acting Antiviral Regimens in Noncirrhotic Patients With Hepatitis C Virus Genotype 1 Infection: An Open-Label, Nonrandomized Trial.},
  author={Anita Kohli and Sarah Kattakuzhy and Sreetha Sidharthan and Amy K Nelson and Mary McLaughlin and Catherine A. Seamon and Eleanor Wilson and Eric G. Meissner and Zayani Sims and Rachel Silk and Chloe Gross and Elizabeth Akoth and Lydia Tang and Angie Price and Tim A. Jolley and Benjamin Emmanuel and Michael A. Proschan and Gebeyehu Teferi and Jose Chavez and Stephen E Abbott and Anu O. Osinusi and Hongmei Mo and Michael A. Polis and Henry Masur and Shyam Kottilil},
  journal={Annals of internal medicine},
  year={2015},
  volume={163 12},
  pages={
          899-907
        }
}

• A. Kohli, S. Kattakuzhy, +22 authors S. Kottilil
• Published 24 November 2015
• Medicine
• Annals of internal medicine

BACKGROUND
Treatment of chronic hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) for 6 weeks achieves sustained virologic response (SVR) rates of 95% in some patients. If effective, shorter therapeutic courses could improve adherence and treatment costs.

OBJECTIVE
To determine factors predictive of SVR to 4 weeks of DAA treatment in patients with stage F0 to F2 liver fibrosis.

DESIGN
Open-label, nonrandomized, phase 2a trial. (Clinical Trials.gov: NCT01805882).

SETTING
Single-center.

PATIENTS
50 treatment-naive and predominantly African American patients with HCV genotype 1 infection and early-stage liver fibrosis were sequentially enrolled into 2 treatment groups.

INTERVENTION
25 participants received a 3-drug regimen consisting of ledipasvir and sofosbuvir plus GS-9451 for 4 weeks, and 25 received a 4-drug regimen consisting of ledipasvir, sofosbuvir, GS-9451, and GS-9669 for 4 weeks.

MEASUREMENTS
The primary efficacy end point was SVR12 (HCV RNA level below the lower limit of quantification at posttreatment week 12).

RESULTS
Forty percent (10 of 25) (95% CI, 21% to 61%) of patients in the 3-drug group and 20% (5 of 25) (CI, 7% to 41%) of those in the 4-drug group achieved SVR12. Exploratory analysis suggested that lower baseline HCV viral load, younger age, and HCV genotype 1b were associated with SVR12. Ten patients had baseline HCV variants conferring greater than 20-fold resistance in vitro to at least 1 study DAA; all had viral relapse. Forty-eight percent (12 of 25) of patients receiving the 3-drug regimen and 72% (18 of 25) of those receiving the 4-drug regimen had adverse events, most of which were mild. One participant was lost to follow-up.

LIMITATION
Nonrandomized study design and small sample of patients with early-stage fibrosis.

CONCLUSION
Combination DAA therapy with 3 or 4 drugs for 4 weeks was well-tolerated but resulted in limited cure rates.

PRIMARY FUNDING SOURCE
National Institute of Allergy and Infectious Diseases, National Cancer Institute, and Clinical Center Intramural Program; supported in part by a cooperative research and development agreement between the National Institutes of Health and Gilead Sciences.