T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients during treatment with interferon alpha plus ribavirin: analysis in a population on effective antiretroviral therapy.
Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.
Arizcorreta
A
A
Servicios de Medicina Interna, Hospital Universitario Puerta del Mar, Cádiz, Spain.
Márquez
M
M
Fernández-Gutiérrez
C
C
Guzmán
E Pérez
EP
Brun
F
F
Rodríguez-Iglesias
M
M
Girón-González
J A
JA
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015329:Gene Rearrangement, T-Lymphocyte; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D016896:Treatment Outcome
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D017493:Leukocyte Common Antigens; C100416:peginterferon alfa-2a