Abstract

ObjectiveImmune changes occurring after primary HIV infection (PHI) have a pivotal relevance. Our objective was to characterize the polyfunctionality of immune response triggered by PHI, and to characterize immune activation and regulatory T cells, correlating such features to disease progression.Patients and MethodsWe followed 11 patients experiencing PHI for 4 years. By polychromatic flow cytometry, we studied every month, for the first 6 months, T lymphocyte polyfunctionality after cell stimulation with peptides derived from HIV-1 gag and nef. Tregs were identified by flow cytometry, and T cell activation studied by CD38 and HLA-DR expression.ResultsAn increase of anti-gag and anti-nef CD8+ specific T cells was observed 3 months after PHI; however, truly polyfunctional T cells, also able to produce IL-2, were never found. No gross changes in Tregs were present. T lymphocyte activation was maximal 1 and 2 months after PHI, and significantly decreased in the following period. The level of activation two months after PHI was strictly correlated to the plasma viral load 1 year after infection, and significantly influenced the length of period without therapy. Indeed, 80% of patients with less than the median value of activated CD8+ (15.5%) or CD4+ (0.9%) T cells remained free of therapy for >46 months, while all patients over the median value had to start treatment within 26 months.ConclusionsT cell activation after PHI, more than T cell polyfunctionality or Tregs, is a predictive marker for the control of viral load and for the time required to start treatment.

Highlights

  • Primary infection with the human immunodeficiency virus type1 (HIV) is a crucial moment for establishing relationships between virus and host [1,2,3]

  • The level of activation two months after primary HIV infection (PHI) was strictly correlated to the plasma viral load 1 year after infection, and significantly influenced the length of period without therapy

  • PHI cohort and viro-immunological parameters CD4+ T cell count and plasma viral load (pVL) were monitored in PHI patients from the first month up to 4 years after infection

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Summary

Introduction

Primary infection with the human immunodeficiency virus type (HIV) is a crucial moment for establishing relationships between virus and host [1,2,3]. High plasma levels of proinflammatory cytokines have been described, along with changes in mitochondrial functionality, augmented tendency to apoptosis and expression of cell death markers (such as CD95) in almost all white blood cells [5,6,7]. Immune activation can promote viral replication, so facilitating the infection of other T cells [9,10]. Several studies, including those in animal models, where primary infection has been experimentally induced and strictly monitored, showed that a strict correlation exists between immune activation and progression of the infection [11]

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