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

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.

Replicative fitness of transmitted HIV-1 drives acute immune activation, proviral load in memory CD4 + T cells, and disease progression

“…We further link the increased activation, exhaustion, and proliferation of T cells to inflammatory cytokine profiles, suggesting a mechanism by which vRC, through induction of an early innate immune response, influences levels of chronic cellular immune activation. This is supported by previously reported associations between CD8 + T-cell activation and the presence of inflammatory cytokines (40,41).…”

Immune responses during spontaneous control of HIV and AIDS: what is the hope for a cure?

“…Moreover, IP-10 and sCD163 levels in HICs predicted the risk of CD4þ decline. Therefore, the association between inflammation and disease progression is similarly present in HICs as in other HIV-infected individuals [11,13].…”

“…Recent studies demonstrate that inflammatory and coagulation biomarkers, such as IL-6, sCD14 and D-dimer, are better correlated with mortality than is T cell activation [11,12]. Moreover, the levels of certain inflammatory molecules during acute infection, such as IP-10, are better predictors of rapid disease progression than viraemia or CD4þ T cell counts [13]. Early virological and immunological features may be strongly prognostic because they reflect the presence of protective host factors (such as HLA-B27) and/or because the balance that is established between the virus and the host during the early phase of infection impacts the subsequent evolution of the infection [14,15] (figure 2).…”

“…Therefore, early treatment seems to diminish inflammation to some extent. It is not clear why the effect was only observed for some inflammatory markers but could be because they are more closely associated with replication levels or earlier and better markers of inflammation [13]. Intensifying treatment in cART-suppressed individuals may help to further reduce residual viral replication and immune activation.…”

Factores asociados a la mortalidad en la población mexicana con SIDA en contraste con otras poblaciones humanas. Revisión sistemática y meta-análisis

“…Varios estudios indican que el desarrollo de enfermedades secundarias o degenerativas parece depender de los grupos raciales. Asimismo, variables en los serotipos circulantes del VIH-1 y combinaciones genéticas en los receptores de quimiocinas han sido relacionados con la rápida progresión del SIDA, aunado a un perfil inmunológico con altos niveles de IL-10 e IL-4, que pronostican una respuesta inmunológica de supresión (Chatterjee, Rathore, Viddyant, Kakkar y Dhole, 2012;Kamat et al, 2012;Liovat et al, 2012;Mahajan et al, 2010;Mosier, 2009). …”