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Clinical Trial
. 2016 Feb 15;62(4):440-447.
doi: 10.1093/cid/civ897. Epub 2015 Oct 26.

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease

Sarah Kattakuzhy  1 , Eleanor Wilson  1 , Sreetha Sidharthan  2 , Zayani Sims  2 , Mary McLaughlin  3 , Angie Price  1 , Rachel Silk  1 , Chloe Gross  1 , Elizabeth Akoth  1 , Maryellen McManus  4 , Benjamin Emmanuel  1 , Shikha Shrivastava  1 , Lydia Tang  1 , Amy Nelson  1 , Gebeyehu Teferi  5 , Jose Chavez  5 , Brian Lam  6 , Hongmei Mo  7 , Anuoluwapo Osinusi  7 , Michael A Polis  8 , Henry Masur  2 , Anita Kohli  9 , Shyamasundaran Kottilil  1
Affiliations
Clinical Trial

Moderate Sustained Virologic Response Rates With 6-Week Combination Directly Acting Anti-Hepatitis C Virus Therapy in Patients With Advanced Liver Disease

Sarah Kattakuzhy et al. Clin Infect Dis. .

Abstract

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.

Chinese clinical trials registration: CT01805882.

Keywords: advanced fibrosis; hepatitis C; short-duration.

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Figures

Figure 1.
Figure 1.
Patient disposition. Abbreviation: eGFR, estimated glomerular filtration rate.
Figure 2.
Figure 2.
Patients with hepatitis C virus (HCV) RNA levels below the lower level of quantification (LLOQ) at various times during treatment and follow-up. Abbreviations: EOT, end of treatment; SVR2, SVR4, and SVR12, sustained virologic response at 2, 4, and 12 weeks after the EOT.
Figure 3.
Figure 3.
Early viral kinetics. Abbreviation: HCV, hepatitis C virus.
See this image and copyright information in PMC

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