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

Abstract

Interferon (IFN)-α 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-α) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-α + 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 mm3 and 874 mm3, 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-α 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.