Does fluvastatin favour HCV replication in vivo? A pilot study on HIV-HCV coinfected patients.
Fluvastatin showed anti-hepatitis C virus (HCV) activity in vitro, through the inhibition of geranylgeranylation of cellular proteins, and a synergistic effect with interferon (IFN)-alpha. Nevertheless statins up-regulate low-density lipoprotein (LDL) receptor, required for HCV cell entry, and the closely related scavenger receptors SRBI and CD36; moreover they reduce class II major histocompatibility complex expression on antigen presenting cell, modulating T-cell activation. In vivo LDL levels have been identified as prognostic indicator of sustained viral response to IFN in patients with HCV infection, suggesting that lipid-lowering agents might conversely favour HCV entry into the hepatocytes and translate into higher viral replication. We evaluated the effect of fluvastatin on HCV-RNA levels, CD36 expression and T-cell homeostasis in HCV-RNA positive patients. HCV-RNA was measured at baseline and after 4 weeks in 42 HCV/HIV-1 co-infected patients, randomized to receive either fluvastatin 80 mg qd or no treatment. CD36 expression and markers of T-cell activation were evaluated by means of flow cytometry. Plasma interleukin (IL)-10, IFN-gamma and IL-7 were measured by ELISA. Serum cholesterol and LDL decreased significantly in the treatment group (P = 0.0001 and 0.01, respectively). Surprisingly a significant increase of HCV-RNA levels was seen after 4 weeks of fluvastatin (P = 0.03). The percentages of naive/activated/apoptotic cells and CD36 expression remained unchanged. Fluvastatin did not inhibit HCV-RNA replication in vivo; conversely we observed a significant increase of HCV-RNA levels. CD36 expression on monocytes were not up-regulated by statins as previously reported in vitro. The correlation between HCV infectivity, oxidized-LDL receptor and statins in HCV infection need further evaluation.
Milazzo
L
L
Section of Infectious Diseases and Immunopathology, Department of Clinical Sciences L Sacco, University of Milan, Milan, Italy. laura.milazzo@unimi.it
Meroni
L
L
Galazzi
M
M
Cesari
M
M
Caramma
I
I
Marchetti
G
G
Galli
M
M
Antinori
S
S
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018955:CD36 Antigens / Q000032:analysis; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D016174:Hepacivirus / Q000187:drug effects / Q000254:growth & development*; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015851:Interleukin-7 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D018955:CD36 Antigens; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D015851:Interleukin-7; D012367:RNA, Viral; D016753:Interleukin-10; D000077340:Fluvastatin; D007371:Interferon-gamma; D002784:Cholesterol