Riassunto analitico
The progression of HIV infection is highly variable among patients, and indeed HIV+ subjects can live up to twenty years without any therapy, or must start treatment after a couple of years. It is known that the immune system plays an important role in controlling the infection, and a fine characterization of the immune changes that occur after infection is assuming a growing relevance. Accordingly, the aim of this study was to identify the events that occur during primary HIV infection (PHI), and their association with viro-immunological parameters and disease progression. By 8 color-polychromatic flow cytometry we analyzed T cell activation and the polyfunctionality of HIV-specific response in lymphocytes from 11 HIV+ patients during PHI and in the following 6 months. Patients have been clinically followed for up to 6 years. Concerning the quality and magnitude of T lymphocytes in response to gag and nef proteins, we observed an increase of CTL activity at 3 months after infection. CD4+ response was present one month after infection, was characterized by CD107a expression, and did not change in the following months. We never observed truly polyfunctional T cells, and in particular we never detected IL-2 production. Moreover, we did not find any association between T cell responses and the control of viral infection, nor with disease progression. T lymphocyte activation (CD38 and HLA-DR expression among T cells) was high at the first and second month after infection, and significantly decreased in the following months, even without therapy. Longitudinal follow up of patients revealed that activation in the second month after infection was strictly linked either to the viral set point at one year after infection, or to the period free of therapy. By Cox analysis we found that activation of both CD4+ and CD8+ T lymphocytes altered the relative risk of survival without therapy (i.e., to reach a value of CD4+ T cells <350 cells/uL). Two months after PHI, 15.5% (median value) of CD8+ were activated. Kaplan Meier analysis showed that 80% of patients with less than this value remained free of therapy for >46 months, while all patients with >15.5% had to start treatment within 26 months. Identical results were obtained considering CD4+, whose median activation value was 0.9%. In conclusion, our main finding is that the quantification of T cell activation is as a predictive marker for the viral setpoint and for the time to treatment.
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