Author:
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Pastor, Lucía; Urrea, Victor; Carrillo, Jorge; Parker, Erica; Fuente Soro, Laura; Jairoce, Chenjerai; Mandomando, Inácio; Naniche, Denise; Blanco, Julià
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Abstract:
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During primary HIV infection (PHI), there is a striking cascade
response of inflammatory cytokines and many cells of the immune
system show altered frequencies and signs of extensive
activation. These changes have been shown to have a relevant
role in predicting disease progression; however, the challenges
of identifying PHI have resulted in a lack of critical
information about the dynamics of early pathogenic events. We
studied soluble inflammatory biomarkers and changes in T-cell
subsets in individuals at PHI (n = 40), chronic HIV infection
(CHI, n = 56), and HIV-uninfected (n = 58) recruited at the
Manhica District Hospital in Mozambique. Plasma levels of 49
biomarkers were determined by Luminex and ELISA. T-cell
immunophenotyping was performed by multicolor flow cytometry.
Plasma HIV viremia, CD4, and CD8 T cell counts underwent rapid
stabilization after PHI. However, several immunological
parameters, including Th1-Th17 CD4 T cells and activation or
exhaustion of CD8 T cells continued decreasing until more than 9
months postinfection. Importantly, no sign of immunosenescence
was observed over the first year of HIV infection. Levels of
IP-10, MCP-1, BAFF, sCD14, tumor necrosis factor receptor-2, and
TRAIL were significantly overexpressed at the first month of
infection and underwent a prompt decrease in the subsequent
months while, MIG and CD27 levels began to increase 1 month
after infection and remained overexpressed for almost 1 year
postinfection. Early levels of soluble biomarkers were
significantly associated with subsequently exhausted CD4 T-cells
or with CD8 T-cell activation. Despite rapid immune control of
virus replication, the stabilization of the T-cell subsets
occurs months after viremia and CD4 count plateau, suggesting
persistent immune dysfunction and highlighting the potential
benefit of early treatment initiation that could limit
immunological damage. |