Abstract
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 Manhiça 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.
Highlights
During primary HIV infection (PHI), many cells of the immune system show signs of extensive activation and a progressive loss of resting subsets [1]
There was no significant difference in age, gender balance, or HIV-RNA viral load (VL) between PHI patients who returned for enrollment and those who were lost to follow-up [34]
A significant negative correlation was observed between IP-10 plasma levels and circulating CD4 T cells at month 2 postinfection (M2); such association was positive and borderline significant between plasma IP-10 levels and CXCR3 + CD4 T cell frequencies, and no association was observed between plasma IP-10 and the frequency of Th1Th17 CD4 T cells
Summary
During primary HIV infection (PHI), many cells of the immune system show signs of extensive activation and a progressive loss of resting subsets [1]. Some studies have reported an increased Treg frequency in lymphoid tissues during progressive HIV disease [25, 26] as shown for SIV infection [27, 28], while others have shown a gradual decline in Tregs in peripheral blood associated with increased immune activation [29,30,31,32]. We provide a longitudinal characterization of different T-cell subsets and the expression of soluble inflammatory biomarkers over the first year after PHI in a cohort of Mozambican adults and compared these changes with chronically HIV-infected (CHI) and HIV-uninfected subjects. We explore the association between the various T-cell phenotypes and the plasma biomarker levels at different stages of infection
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