Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv. Viral Hepatitis Summit April 10â12 2015, Shanghai, China. Oral Abstracts. OP0001.
Journal of Clinical Virology 69 (2015) 247–250
Contents lists available at ScienceDirect
Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv
Viral Hepatitis Summit April 10–12 2015, Shanghai, China Oral Abstracts
OP0001 Dose-dependent decrease in hepatitis delta virus (HDV) RNA achieved with the oral prenylation inhibitor lonafarnib in a proof-of-concept, randomised, double-blinded, placebo-controlled study in patients with chronic HDV infection C. Koh a , L. Canini b,c , H. Dahari b,d , S. Cooper e , D. Cory f , M.A. Winters g , I. Choong f , S.J. Cotler b , D.E. Kleiner h , C. Yurdaydin i , T. Heller a , J.S. Glenn g,∗ a
Liver Diseases Branch, NIDDK, NIH, USA Division of Hepatology, Department of Medicine, Loyola University Medical Center, USA c Institute of Evolutionary Biology, University of Edinburgh, UK d Theoretical Biology and Biophysics, Los Alamos National Laboratory, USA e Division of Hepatology, California Pacific Medical Center, USA f Eiger Biopharmaceuticals, USA g Division of Gastroenterology and Hepatology, Department of Microbiology and Immunology, Stanford University School of Medicine, USA h Laboratory of Pathology, NCI, NIH, USA i Department of Gastroenterology, University of Ankara Medical School, Turkey b
Background: Current treatment for hepatitis delta virus (HDV) infection is inadequate. Prenylation is essential for HDV particle assembly, and prenylation inhibitors abrogate HDV production in in vitro and in vivo models. We sought to test the hypothesis that targeting prenylation can inhibit HDV infections in people by doing the first proof-of-concept study of the oral prenylation inhibitor lonafarnib, evaluating its safety and antiviral efficacy. Methods: We did a phase 2a, double-blinded, randomised, placebo-controlled study in two groups of chronically infected HDV patients. Participants received lonafarnib 100 mg (group 1) or 200 mg (group 2) twice daily for 28 days and were then followed up for 6 months. Both groups enrolled six patients receiving treatment and two patients receiving placebo. Serial measurements of safety
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parameters, liver tests, pharmacokinetics, and virological markers were done. Findings: 71% of patients were men, median age was 38 years, and ethnic groups included Asian (50%), Caucasian (43%), and African (7%). There were no significant differences in baseline parameters between groups. At day 28, compared with placebo, mean log HDV RNA change from baseline was −0.73 log IU/mL in group 1 (p = 0.04) and −1.54 log IU/mL in group 2 (p = 0.002). Lonafarnib serum concentrations correlated with HDV RNA change (r2 = 0.78, p < 0.0001). Biphasic viral kinetic declines were observed with a substantially shorter delay in onset of the first phase (t0 = 1 day) and HDV half-life (t1/2 = 1.4 days) than with peg-interferon (t0 = 8.5 days, HDV t1/2 = 2.9 days; Hepatology 2014;60:190210). There was no evidence of virological resistance. Adverse events were mild to moderate (including nausea, vomiting, dyspepsia, anorexia, diarrhoea and weight loss) and prompted no treatment discontinuations. Interpretation: This is the first study to show that treatment of delta hepatitis with the prenylation inhibitor lonafarnib significantly reduces HDV levels. Declines in viral infection significantly correlated with serum drug levels, providing further evidence for the efficacy of prenylation inhibition in HDV. http://dx.doi.org/10.1016/j.jcv.2015.06.071 OP0002 Natural polymorphisms conferring resistance to NS3/4A protease inhibitors in treatment-naïve HIV/HCV coinfected patients in China: A cross-sectional study K. Zhou a,∗ , Z. Liang a , C. Wang c , C. Ning a , Y. Lan a , W. Cai a , F. Hu a , J.D. Tucker a,b a
Guangzhou Eighth People’s Hospital, China UNC Chapel Hill School of Medicine, USA c Brown University School of Medicine, USA b
Background: Coinfection with chronic hepatitis C virus (HCV) and HIV is estimated to impact 5 million individuals worldwide. The advent of direct-acting agents has enabled earlier and better tolerated treatment for HCV in HIV coinfection, but has been limited by the development of drug resistance. This study extends knowledge regarding the prevalence of natural polymorphisms conferring resistance to NS3/4A protease inhibitors in
