Open-label Phase 1b pilot study to assess the antiviral efficacy of simvastatin combined with sertraline in chronic hepatitis C patients

Keyur Patel, Seng G. Lim, Chow W. Cheng, Eric Lawitz, Hans L. Tillmann, Narinder Chopra, Ralf Altmeyer, John C.R. Randle, John G. McHutchison

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Background: 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors inhibit HCV replication in vitro. The combination of sertraline and simvastatin has synergistic antiviral activity in vitro, but there are no prior in vivo studies. Our aims were to prospectively assess the antiviral efficacy and safety of this drug combination in chronic hepatitis C (CHC) patients. Methods: A total of 15 CHC adults (including 1 control subject) that were treatment-naive or prior partial responders/relapsers to standard-of-care therapy were enrolled at four centres (2 in Singapore and 2 in the US). Patients received simvastatin 40 mg once daily and sertraline 50 mg once daily for 7 days, and then 80 mg once daily and 100 mg once daily, respectively, for another 21 days with a 14-day follow-up. Results: Of the 15 CHC patients, 13 completed the study. Subjects were mostly Caucasian (8/15), mean age 49.1 ±9 years and the genotype distribution was 1=10, 2=2 and 3=3. No subject discontinued dosing due to adverse events. Mean HCV RNA change from baseline was from -0.005 to -0.236 log 10 IU/ml across study intervals. Three subjects had transient >1 log 10 HCV RNA declines. No subject achieved >2 log 10 HCV RNA decline. Conclusions: The combination of sertraline and simvastatin is well-tolerated over the short-term, but has no significant antiviral or anti-inflammatory response in CHC patients. This may reflect in vivo differences in synergy between statin and/or selective serotonin reuptake inhibitors and incomplete inhibition of membrane protein prenylation with statin therapy.

Original languageEnglish (US)
Pages (from-to)1341-1346
Number of pages6
JournalAntiviral Therapy
Volume16
Issue number8
DOIs
StatePublished - Dec 19 2011
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Patel, K., Lim, S. G., Cheng, C. W., Lawitz, E., Tillmann, H. L., Chopra, N., Altmeyer, R., Randle, J. C. R., & McHutchison, J. G. (2011). Open-label Phase 1b pilot study to assess the antiviral efficacy of simvastatin combined with sertraline in chronic hepatitis C patients. Antiviral Therapy, 16(8), 1341-1346. https://doi.org/10.3851/IMP1898