T-Cell surface CCR5 density is not correlated with hepatitis severity in hepatitis C virus/HIV-coinfected individuals: implications for the therapeutic use of CCR5 antagonists.
CCR5 antagonists represent promising anti-HIV agents. Yet, if the CCR5 chemokine receptor plays a positive role in hepatitis C virus (HCV) infection, CCR5 antagonists might be contraindicated in HCV/HIV-coinfected subjects. Therefore, we tested the hypothesis that the level of T-cell surface CCR5 expression, which might determine the intensity of HCV-specific T-cell recruitment into the liver, and thereby the efficiency of the anti-HCV response, could determine HCV disease evolution. For this purpose, we compared CCR5 density, measured by quantitative flow cytometry at the surface of nonactivated (human leukocyte antigen-D-related [HLA-DR]-) T cells of 51 HCV/HIV patients, with HCV load, serum aminotransferase levels, and liver histology (inflammatory activity, fibrosis, and rate of fibrosis progression). DR-CD4+ T-cell surface CCR5 density, which correlated with DR-CD8+ T-cell surface CCR5 density and was stable over time in HCV/HIV-coinfected individuals, did not correlate with any of the biologic parameters of HCV infection analyzed and was not linked to the capacity to clear the virus. In conclusion, we failed to demonstrate any impact of interindividual variability in T-cell surface CCR5 density on HCV infection, which would have argued against the use of CCR5 antagonists in HIV/HCV-coinfected subjects.
Vincent
Thierry
T
Institut de Génétique Humaine, CNRS UPR 1142, Montpellier, France.
Portales
Pierre
P
Baillat
Vincent
V
de Boever
Corinne Merle
CM
Le Moing
Vincent
V
Vidal
Michèle
M
Ducos
Jacques
J
Clot
Jacques
J
Reynes
Jacques
J
Corbeau
Pierre
P
D000328:Adult; D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D016174:Hepacivirus / Q000302:isolation & purification / Q000502:physiology; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*; D000637:Transaminases / Q000097:blood; D019562:Viral Load
D065100:CCR5 Receptor Antagonists; D015704:CD4 Antigens; D016827:CD8 Antigens; D006684:HLA-DR Antigens; D019713:Receptors, CCR5; D000637:Transaminases