Atorvastatin does not exhibit antiviral activity against HCV at conventional doses: a pilot clinical trial.
Cholesterol biosynthesis is an integral part of HCV RNA replication. Not only does HCV RNA replicate on lipid rafts, but it also requires cholesterol intermediates to replicate. In addition, it has been shown in vitro that several HMG-CoA reductase inhibitors can decrease HCV RNA replication by > or = 1 log. Therefore, we designed a clinical trial to evaluate the effect of atorvastatin on HCV RNA levels. In this prospective clinical trial, where patients served as their own control, 10 HCV-infected patients who required treatment for high cholesterol were given 20 mg atorvastatin per day. Although serum cholesterol and LDL predictably decreased significantly, there was no statistically significant change in week 4 and week 12 HCV RNA levels compared to pretreatment HCV RNA levels by the paired Student t test. It is unclear whether the addition of an HMG-CoA reductase inhibitor to interferon or a more potent inhibitor of cholesterol biosynthesis may be required to inhibit HCV RNA replication in vivo. In conclusion, atorvastatin, and likely all HMG-CoA reductase inhibitors, does not inhibit HCV RNA replication in vivo at conventional doses.
O'Leary
Jacqueline G
JG
Gastrointestinal Unit, Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
Chan
Jessica L
JL
McMahon
Cory M
CM
Chung
Raymond T
RT
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D005260:Female; D016174:Hepacivirus / Q000187:drug effects*; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin