Acute pro- and anti-inflammatory plasma biomarkers of T cell activation setpoint levels and disease progression in HIV-1 infection

Background: Chronic immune activation (IA) and viral load (VL) reach respectively an immunological and viral setpoint after acute infection, which are predictive of disease progression. It is unknown what determines the immunological setpoint. We tested whether during acute infection, patients progressing slowly present less pro-inflammatory and/or more anti-inflammatory soluble factors in their plasma than progressors.
Methods: Forty-six untreated patients, enrolled in the ANRS Primo cohort, have been divided into rapid progressors (RP, N=16), progressors (P, N=19), slow progressors (SP, N=11). Seventeen healthy donors (HD) were recruited. The study was approved by the national Ethics Committee. Plasma was analyzed at recruitment (M0), one (M1) and six (M6) months later. Twenty-seven pro-inflammatory and two anti-inflammatory cytokines were quantified by Luminex or Elisa. Statistical analyses comprised Mann & Whitney, Spearman's rank correlations, and linear regressions.
Results: During acute infection (M0), 8 soluble factors were increased for RP (IL-1b, TNF-a, IL-18, IP-10, IL-10, IL-18, sTRAIL, sIL2Ra), 4 for P (IP-10, IL-10, IL-18, sTRAIL) and 4 for SP (IL-18, sIL2Ra, sTRAIL, MCP-1) compared to HD. Only RP and P showed increased levels of IP-10 and IL-10. No cytokine during acute infection was identified as predictor for VL at M6. By contrast, during acute infection, MCP-1 and IP-10 predicted 45% of the variation of T CD4+ counts at M6, while TGF-b1 and IL-18 were both positively associated with IA (TCD8+CD38+HLA-DR+) at M6, predicting 74% of the variation.
Conclusion: RP and P showed both a significant increase of pro-inflammatory and anti-inflammatory soluble factors in their plasma. In addition, during PI, the soluble factors associated with IA and T CD4+ counts at the immunological setpoint were respectively IL-18, TGF-b1 and IP-10, MCP-1. The quantification of such soluble factors in plasma during acute infection could lead to better understanding of early stages of the disease and by consequence to prevent its progression.

A.-S. Liovat1, M.-A. Rey-Cuille2,3, C. Lecuroux4,5, B. Jacquelin1, I. Girault4,5, P. Lebon6,7, G. Petitjean1, C. Deveau5,8, F. Barré-Sinoussi1, M. Sinet4,5, M.C. Muller-Trutwin1, and the ANRS PRIMO Study Group
1Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France, 2Institut Pasteur, Unité de Recherche et Expertise Epidémiologie des Maladies Emergentes, Paris, France, 3CNRS, Paris, France, 4Inserm, U802, Paris, France, 5Université Paris-Sud, Paris, France, 6Hôpital Saint-Vincent de Paul, Paris, France, 7Universté Paris Descartes, Laboratoire de Virologie, Paris, France, 8INSERM, U822, Paris, France