E remained free of therapy for .48 months, while all get KDM5A-IN-1 patients above the median had to start treatment within 26 months (not shown).DiscussionAcute, primary HIV Oltipraz chemical information infection has a crucial importance in determining the entire course of the disease, since in this phase the immune activation set point predicts the loss of CD4+ T lymphocytes [2]. Indeed, it has been shown that the level of CD4+ and CD8+ T cell activation during acute infection is able to influence the level of HIV viremia, that the level of CD8+ T 25033180 cells that express the activation marker CD38 predicts the loss of CD4+ T cells [35], and that not only the reduction of viremia by antiretroviral treatment reduces immune activation and inflammatory phenomena, but also that the reduction of T cell activation by anti-inflammatory drugs can reduce viremia [36]. A strong immune activation, that includes the production of proinflammatory cytokines and rapid destruction of CD4+ T cells that reside in the gut-associated lymphoid tissue, favors massive replication of the virus and its dissemination in lymphoid tissues. In turn, the impaired local cellular immunity favors damages to the gastrointestinal mucosa, allowing the translocation of microbial products, including LPS, which contribute to persistent inflammation through the activation of Toll like receptors. Furthermore, self-molecules containing the so-called “damageassociated molecular pattern”, or alarmins, that include mitochondrial proteins and mitochondrial DNA [37], can further activate inflammatory pathways and increase the damages [38,39]. Gaining information on the events that occur during primary infection is thus crucial to find strategies that can either arrest the initial virus spread, or rescue host cells. To better understand the importance of immune activation in determining the course ofFigure 8. Association between the frequency of activated T cells (either CD4+ or CD8+) measured at M2, and plasma viral load, analyzed 1 year after PHI. Activated cells were identified as described in the legend to Figure 6. doi:10.1371/journal.pone.0050728.gTrend of T cell activationThe activation of CD4+ and CD8+ T cells was studied taking into account the co-expression of HLA-DR and of high levels of CD38 (CD38bright), as described [7]. Figure 6 (upper panel, referred to CD4+, and lower panel, referred to CD8+ T cells) shows a high level of activation at M1 and M2, and a significant decrease in the following period.T cell activation after PHI is a predictive marker for viral setpoint and length of the period without therapyFigure 7 shows that a direct correlation was present between the level of CD4+ T cell activation status and pVL levels, at all months analyzed. As reported in Figure 8, a direct association was then found between the frequency of activated T cells (either CD4+ or CD8+) measured at M2, and plasma viral load, analyzed 1 year after PHI.Biomarkers of HIV Control after PHIFigure 9. Association between CD4+ or CD8+ T cell activation at M2 and M3 and the length of the period free of therapy. Activated cells were identified as described in the legend to Figure 6. doi:10.1371/journal.pone.0050728.gHIV infection, we have performed a longitudinal study in a group of patients in whom several immune parameters were studied for six months after primary infection, and who were then followed for up to 5 years. We analyzed both the subtype and magnitude of specific T lymphocytes that respond to the viral proteins gag and nef, an.E remained free of therapy for .48 months, while all patients above the median had to start treatment within 26 months (not shown).DiscussionAcute, primary HIV infection has a crucial importance in determining the entire course of the disease, since in this phase the immune activation set point predicts the loss of CD4+ T lymphocytes [2]. Indeed, it has been shown that the level of CD4+ and CD8+ T cell activation during acute infection is able to influence the level of HIV viremia, that the level of CD8+ T 25033180 cells that express the activation marker CD38 predicts the loss of CD4+ T cells [35], and that not only the reduction of viremia by antiretroviral treatment reduces immune activation and inflammatory phenomena, but also that the reduction of T cell activation by anti-inflammatory drugs can reduce viremia [36]. A strong immune activation, that includes the production of proinflammatory cytokines and rapid destruction of CD4+ T cells that reside in the gut-associated lymphoid tissue, favors massive replication of the virus and its dissemination in lymphoid tissues. In turn, the impaired local cellular immunity favors damages to the gastrointestinal mucosa, allowing the translocation of microbial products, including LPS, which contribute to persistent inflammation through the activation of Toll like receptors. Furthermore, self-molecules containing the so-called “damageassociated molecular pattern”, or alarmins, that include mitochondrial proteins and mitochondrial DNA [37], can further activate inflammatory pathways and increase the damages [38,39]. Gaining information on the events that occur during primary infection is thus crucial to find strategies that can either arrest the initial virus spread, or rescue host cells. To better understand the importance of immune activation in determining the course ofFigure 8. Association between the frequency of activated T cells (either CD4+ or CD8+) measured at M2, and plasma viral load, analyzed 1 year after PHI. Activated cells were identified as described in the legend to Figure 6. doi:10.1371/journal.pone.0050728.gTrend of T cell activationThe activation of CD4+ and CD8+ T cells was studied taking into account the co-expression of HLA-DR and of high levels of CD38 (CD38bright), as described [7]. Figure 6 (upper panel, referred to CD4+, and lower panel, referred to CD8+ T cells) shows a high level of activation at M1 and M2, and a significant decrease in the following period.T cell activation after PHI is a predictive marker for viral setpoint and length of the period without therapyFigure 7 shows that a direct correlation was present between the level of CD4+ T cell activation status and pVL levels, at all months analyzed. As reported in Figure 8, a direct association was then found between the frequency of activated T cells (either CD4+ or CD8+) measured at M2, and plasma viral load, analyzed 1 year after PHI.Biomarkers of HIV Control after PHIFigure 9. Association between CD4+ or CD8+ T cell activation at M2 and M3 and the length of the period free of therapy. Activated cells were identified as described in the legend to Figure 6. doi:10.1371/journal.pone.0050728.gHIV infection, we have performed a longitudinal study in a group of patients in whom several immune parameters were studied for six months after primary infection, and who were then followed for up to 5 years. We analyzed both the subtype and magnitude of specific T lymphocytes that respond to the viral proteins gag and nef, an.
