Plasma levels of soluble CD27: a simple marker to monitor immune activation during potent antiretroviral therapy in HIV-1-infected subjects

Author:

DE MILITO A1,ALEMAN S2,MARENZI R1,SÖNNERBORG A2,FUCHS D3,ZAZZI M4,CHIODI F1

Affiliation:

1. Microbiology and Tumourbiology Centre, Karolinska Institutet, Stockholm

2. Division of Clinical Virology, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden

3. Institute for Medical Chemistry and Biochemistry, University of Innsbruck and Ludwig Boltzmann Institute of AIDS Research, Innsbruck, Austria

4. Division of Microbiology, Department of Molecular Biology, University of Siena, Siena, Italy

Abstract

SUMMARY Plasma levels of soluble CD27 (sCD27) are elevated in diseases characterized by T cell activation and are used as a marker of immune activation. We assessed the usefulness of determining plasma sCD27 as a marker for monitoring immune activation in HIV-1-infected patients treated with highly active antiretroviral therapy (HAART). A first cross-sectional examination of 68 HIV-1-infected and 18 normal subjects showed high levels of sCD27 in HIV-1 infection; plasma sCD27 was correlated to HIV-1 viraemia and inversely correlated to CD4+ T cell count. Twenty-six HIV-1-infected patients undergoing HAART were studied at baseline and after 6, 12, 18 and 24 months of therapy. Seven additional patients under HAART were analysed at baseline, during and after interruption of therapy. In the total population, HAART induced a significant and progressive reduction, but not a normalization, of plasma levels of sCD27 after 24 months. A full normalization of plasma sCD27 was observed in the virological responders (undetectable HIV-1 RNA at months 18 and 24) and also in patients with moderate immunodeficiency at baseline (CD4+ T cell count >200 cells/mm3). Changes in plasma neopterin paralleled the changes in sCD27 but only baseline sCD27 levels were predictive of a greater increase in CD4+ T cell count during the follow-up. Discontinuation of therapy resulted in a rapid increase of sCD27 plasma levels associated with viraemia rebound and drop in CD4+ T cell count. Our findings suggest that plasma sCD27 may represent an alternative and simple marker to monitor immune activation during potent antiretroviral therapy. HIV-1-induced immune activation can be normalized by HAART in successfully treated patients where the disease is not advanced.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

Reference49 articles.

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