Acute plasma biomarkers of T cell activation set-point levels and of disease progression in HIV-1 infection.

Anne-Sophie Liovat,Pierre Lebon,Alain Venet,Isabelle Girault,Yasmine Zitoun,Laurence Meyer,Françoise Barré-Sinoussi,Béatrice Jacquelin,Gaël Petitjean,Camille Lécuroux,Marie-Anne Rey-Cuillé,Michaela Müller-Trutwin,Martine Sinet

doi:10.1371/journal.pone.0046143

Abstract

T cell activation levels, viral load and CD4+ T cell counts at early stages of HIV-1 infection are predictive of the rate of progression towards AIDS. We evaluated whether the inflammatory profile during primary HIV-1 infection is predictive of the virological and immunological set-points and of disease progression. We quantified 28 plasma proteins during acute and post-acute HIV-1 infection in individuals with known disease progression profiles. Forty-six untreated patients, enrolled during primary HIV-1 infection, were categorized into rapid progressors, progressors and slow progressors according to their spontaneous progression profile over 42 months of follow-up. Already during primary infection, rapid progressors showed a higher number of increased plasma proteins than progressors or slow progressors. The plasma levels of TGF-β1 and IL-18 in primary HIV-1 infection were both positively associated with T cell activation level at set-point (6 months after acute infection) and together able to predict 74% of the T cell activation variation at set-point. Plasma IP-10 was positively and negatively associated with, respectively, T cell activation and CD4+ T cell counts at set-point and capable to predict 30% of the CD4+ T cell count variation at set-point. Moreover, plasma IP-10 levels during primary infection were predictive of rapid progression. In primary infection, IP-10 was an even better predictor of rapid disease progression than viremia or CD4+ T cell levels at this time point. The superior predictive capacity of IP-10 was confirmed in an independent group of 88 HIV-1 infected individuals. Altogether, this study shows that the inflammatory profile in primary HIV-1 infection is associated with T cell activation levels and CD4+ T cell counts at set-point. Plasma IP-10 levels were of strong predictive value for rapid disease progression. The data suggest IP-10 being an earlier marker of disease progression than CD4+ T cell counts or viremia levels.

Highlights

Several months after HIV-1 infection, blood CD4+ T cell counts, plasma RNA viral load (VL) and CD8+ T cell activation levels reach the so-called set-point
HIV-1 Infected Individuals Enrolled in primary HIV infection (PHI) and their Disease Progression Characteristics
In order to search whether there is an association between early inflammatory profiles and disease progression, we quantified a wide range of proteins (N = 28) in the plasma of a cohort of 46 patients (Table S1)

Summary

Introduction

Several months after HIV-1 infection, blood CD4+ T cell counts, plasma RNA viral load (VL) and CD8+ T cell activation levels reach the so-called set-point. At this set-point, which is generally reached after six months post-infection, the levels of the virological and immunological markers, in particular T cell activation levels, are predictive of the rapidity of disease progression [1,2,3,4,5]. New early markers for disease progression could help to determine if an early initiation of treatment is desirable in those patients who are diagnosed during PHI. Further insight into the early events during HIV-1 infection can help to better understand the mechanisms leading to systemic T cell activation and progressive loss of blood CD4+ T cells

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Conclusion