Acute Plasma Biomarkers of T Cell Activation Set-Point Levels and of Disease Progression in HIV-1 Infection

Anne-Sophie Liovat (1) , Marie-Anne Rey-Cuillé (2) , Camille Lecuroux (3) , Béatrice Jacquelin (1) , Isabelle Girault (3) , Gaël Petitjean (1) , Yasmine Zitoun (4, 5) , Alain Venet (3) , Françoise Barré-Sinoussi (1) , Pierre Lebon (6, 7) , Laurence Meyer (4, 5) , Martine Sinet (3) , Michaela Muller-Trutwin (1)

1 Régulation des Infections Rétrovirales
2 Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology
3 Régulation de la réponse immune, infection VIH-1 et autoimmunité
4 Service de santé publique et d'épidémiologie
5 Hôpital Necker - Enfants Malades [AP-HP]
6 UPD5 - Université Paris Descartes - Paris 5
7 Hôpital Cochin [AP-HP]

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-b1 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.

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Immunologie; Maladies infectieuses; Microbiologie et Parasitologie; Virologie

Anne-Sophie Liovat, Marie-Anne Rey-Cuillé, Camille Lecuroux, Béatrice Jacquelin, Isabelle Girault, et al.. Acute Plasma Biomarkers of T Cell Activation Set-Point Levels and of Disease Progression in HIV-1 Infection. PLoS ONE, 2012, 7 (10), pp.e46143. ⟨10.1371/journal.pone.0046143⟩. ⟨pasteur-01968867⟩