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Clinical Trial
. 2002 Mar;127(3):486-94.
doi: 10.1046/j.1365-2249.2002.01786.x.

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

A De Milito  1 , S Aleman, R Marenzi, A Sonnerborg, D Fuchs, M Zazzi, F Chiodi
Affiliations
Clinical Trial

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

A De Milito et al. Clin Exp Immunol. 2002 Mar.

Erratum in

  • Clin Exp Immunol. 2003 Oct;134(1):167. D Fuchs [corrected to Fuchs D]

Abstract

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.

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Figures

Fig. 1
Fig. 1
Correlation analysis between HIV viral load (a,b), CD4+ T cells (c,d) and plasma sCD27 (n = 68, a,c) and neopterin (n = 26, b,d). The analysis was performed with the Spearman rank correlation test.
Fig. 2
Fig. 2
Longitudinal analysis of the sCD27 (a,b,c) and neopterin (d,e,f) plasma levels in 26 patients undergoing HAART. In panels (a) and (d) six untreated patients (◊) are shown in addition to patients undergoing HAART (■). Panels (b) and (e) show patients grouped as moderately (MOD, n = 11) □, or severely (SEV, n = 15) ■, immunocompromised at baseline. In panels (c) and (f) patients were grouped into virological responders (n = 16) □, and non-responders (n = 10) ■, to HAART. Data are indicated as mean ± s.e.m. The dotted areas indicate the cut-off value of 200 U/ml for plasma sCD27 and 8·7 nmol/l for neopterin.
Fig. 3
Fig. 3
Correlation analysis between absolute change of CD4+ T cells after 24 months of therapy and plasma sCD27 (a) and plasma neopterin (b). Plasma sCD27 is measured as U/ml, neopterin as nmol/l and CD4+ T counts as cells/mm3. Analysis was performed with Spearman’s rank correlation test.
Fig. 4
Fig. 4
Changes in HIV-1 RNA (copies/ml, formula image), CD4+ T cell count (cells/mm3, –•–), plasma sCD27 (U/ml,□) and plasma neopterin (nmol/l, ×) during therapy in four patients representative of the MOD group (a), SEV group (b), responders (c) and non-responders (d).
Fig. 5
Fig. 5
Longitudinal analysis of plasma sCD27 after interruption of HAART. Seven patients (C1-C7) were analysed at baseline, after 14 months of HAART and 4 months after interrupting therapy. Plasma sCD27 (U/ml, •) and CD4+ T cells (cells/mm3, ◊) are plotted on the left y axis and HIV-1 RNA (log copies/ml, ○) on the right y axis.
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