Fic CD4+ T cells, or in the percentages of both nef-specific CD4+ and CD8+ T cells over time. Regarding the quality of T cell specific GSK429286A response to gag (Figure 3, upper part), we found that at all the time points .50 of gagspecific CD4+ T lymphocytes were CD107a; only a low percentage was CD154+ or CD154+,IFN-c+. IL-2 production was detectable only at M6, and in a negligible amount of cells. Figure 3, lower part, shows that gag-specific CD8+ T lymphocytes were predominantly CD107a+, and many of them also produced IFN-c at all time points. IL-2 production was almost never detected. A significant trend over time was observed in both CD107a+,IFN-c+ (p = 0.0011) and CD107a single positive(p = 0.0247) CD8+ T cells, with an increase at M2 and M3 and a reduction in the following months. Figure 4 (upper part) shows that also nef-specific CD4+ T cell response was characterized a relevant 23727046 expression of CD107a; only a small amount of cells were able to express CD154 or to produce IFN-c; IL-2 production was almost never detected. The nefspecific CD8+ T cell response (Figure 4, lower part) was similar to that observed for gag: a large proportion of cells were CD107a+ and/or IFN-c+, while a negligible amount of cells expressed CD154 or produced IL-2.Treg frequency returns to baseline level 6 months after HIV infectionWe analyzed the frequency and absolute number of Tregs, defined as CD3+,CD4+,CD25++,CD1272,FoxP3+ cells. As shown in Figure 5, the frequency of CD4+ T cell with regulatory phenotype increased over time (upper panel). However, the absolute number of Treg did not change significantly (middle panel), as well as the amount of Treg showing an activated phenotype (i.e., those expressing HLA-DR, lower panel).Biomarkers of HIV Control after PHIFinally, an inverse association between CD4+ or CD8+ T cell order GSK2879552 activation at M2 and M3 and the length of the period free of therapy was also found (Figure 9).Activation of CD8+ T cells predicts the length of the period without therapyWe analyzed the role of CD8+ T cell activation in predicting the length of the period without treatment, and performed a “drug free” survival analysis in which we considered the importance of T cell activation in influencing the length of the period that did not require any treatment, i.e. from PHI to the failure of virological control (the time of starting HAART). Figure 10 (upper part) shows time free of therapy of all our patients, performed by Kaplan Meyer analysis: 25 of patients failed (i.e., had to start therapy) within 18 months of HIV infection, and 50 within 26 months. Five out of 11 patients were still out of therapy 48 months after PHI. Two months after PHI, the median percentage of activated CD8+ T cells was 15.5 , that of CD4+ T cells was 0.9 . By Cox analysis, we found that activation of CD8+ T cells had a significant impact on the risk of starting therapy (Hazard ratio = 1.124 p.|z| = 0.013; 95 Conf. Interval: 1.030?1.232): the increase in one unit of CD8 activation leads to an increase in the instantaneous risk of 2.5 to 23 . As shown in Figure 10 (lower part), we found that all patients with values of activated CD8+ T cells above the median (5 out of 11) had to start therapy within 26 months from PHI. Five out of 6 whose values of CD8+ T cell activation were below the median were still out of therapy for more than 48 months. It is to note that identical results were obtained considering activated CD4+ T cells: 80 of patients with less than the median valu.Fic CD4+ T cells, or in the percentages of both nef-specific CD4+ and CD8+ T cells over time. Regarding the quality of T cell specific response to gag (Figure 3, upper part), we found that at all the time points .50 of gagspecific CD4+ T lymphocytes were CD107a; only a low percentage was CD154+ or CD154+,IFN-c+. IL-2 production was detectable only at M6, and in a negligible amount of cells. Figure 3, lower part, shows that gag-specific CD8+ T lymphocytes were predominantly CD107a+, and many of them also produced IFN-c at all time points. IL-2 production was almost never detected. A significant trend over time was observed in both CD107a+,IFN-c+ (p = 0.0011) and CD107a single positive(p = 0.0247) CD8+ T cells, with an increase at M2 and M3 and a reduction in the following months. Figure 4 (upper part) shows that also nef-specific CD4+ T cell response was characterized a relevant 23727046 expression of CD107a; only a small amount of cells were able to express CD154 or to produce IFN-c; IL-2 production was almost never detected. The nefspecific CD8+ T cell response (Figure 4, lower part) was similar to that observed for gag: a large proportion of cells were CD107a+ and/or IFN-c+, while a negligible amount of cells expressed CD154 or produced IL-2.Treg frequency returns to baseline level 6 months after HIV infectionWe analyzed the frequency and absolute number of Tregs, defined as CD3+,CD4+,CD25++,CD1272,FoxP3+ cells. As shown in Figure 5, the frequency of CD4+ T cell with regulatory phenotype increased over time (upper panel). However, the absolute number of Treg did not change significantly (middle panel), as well as the amount of Treg showing an activated phenotype (i.e., those expressing HLA-DR, lower panel).Biomarkers of HIV Control after PHIFinally, an inverse association between CD4+ or CD8+ T cell activation at M2 and M3 and the length of the period free of therapy was also found (Figure 9).Activation of CD8+ T cells predicts the length of the period without therapyWe analyzed the role of CD8+ T cell activation in predicting the length of the period without treatment, and performed a “drug free” survival analysis in which we considered the importance of T cell activation in influencing the length of the period that did not require any treatment, i.e. from PHI to the failure of virological control (the time of starting HAART). Figure 10 (upper part) shows time free of therapy of all our patients, performed by Kaplan Meyer analysis: 25 of patients failed (i.e., had to start therapy) within 18 months of HIV infection, and 50 within 26 months. Five out of 11 patients were still out of therapy 48 months after PHI. Two months after PHI, the median percentage of activated CD8+ T cells was 15.5 , that of CD4+ T cells was 0.9 . By Cox analysis, we found that activation of CD8+ T cells had a significant impact on the risk of starting therapy (Hazard ratio = 1.124 p.|z| = 0.013; 95 Conf. Interval: 1.030?1.232): the increase in one unit of CD8 activation leads to an increase in the instantaneous risk of 2.5 to 23 . As shown in Figure 10 (lower part), we found that all patients with values of activated CD8+ T cells above the median (5 out of 11) had to start therapy within 26 months from PHI. Five out of 6 whose values of CD8+ T cell activation were below the median were still out of therapy for more than 48 months. It is to note that identical results were obtained considering activated CD4+ T cells: 80 of patients with less than the median valu.
