Therefore, ideally HIV-infected individuals should be identified and encouraged to initiate ART as soon as possible, in order to avoid the destruction of thymic function. HIV infection evoked a generalized activation of the immune system, and a higher level of T-cell activation has been associated with a reduced recovery of the CD4+T-cell counts, increased mortality, and cardiovascular diseases.[16,21C23,37C40] Abnormal activation can increase HIV replication promote cell apoptosis, accelerate cell senescence, and cellular exhaustion, and it has also been associated with the HIV reservoir size.[41C43] We observed that although the activation of CD4+T cells was less intensive in individuals with early ART than in those receiving later ART, it still remained elevated when compared with NC. those with later ART (was used to compare between 2 groups of subjects. The KruskalCWallis and MannCWhitney tests were used to compare among the multiple groups of subjects. All tests were 2-tailed, and P?.05 was considered significant. 3.?Results 3.1. Trajectories of CD4+T-cell counts during early ART and later ART To investigate whether the recovery of CD4+T-cell counts was better in early ART, we examined the kinetic changes of CD4+T-cell counts both in early ART and later ART. After 30 months of ART, CD4+T-cell counts of FSCN1 all the 78 patients increased from 243 to 413 cells/L. The elevation in CD4+T-cell counts was most prominent during the first 3 months after ART initiation (mean change 136 cells/L). After the first 3 months, CD4+T-cell counts became relatively stable (Fig. ?(Fig.11A). Open in a separate window Figure 1 Trajectories of CD4+T-cell counts during early antiretroviral therapy (ART) and later ART. (A) Trajectory of CD4+T-cell counts in patients with ART (n?=?78, mean values??standard deviation (SD) are shown in the figure). (B) Trajectories of CD4+T-cell counts in individuals initiating ART??6 months of infection (early ART, red, n?=?33), or 1 years after initial infection (later ART, blue, n?=?45, mean values are shown in figure). (C) Monthly changes of CD4+T-cell counts (CD4+T/month) were compared between early ART (red, n?=?33) and later ART (blue, n?=?45) (mean values??SD are shown in figure). Contribution of individuals with different CD4+T-cell changes (CD4+T) to the overall total after 12 months of early ART (D) or later ART (E). ?P?.05, ??P?.01. Compared with later ART, CD4+T-cell counts in early ART were always higher (Fig. ?(Fig.1B).1B). Monthly changes of CD4+T-cell count from baseline (CD4+T/month) in early ART were higher than those in later ART during the 1st month (143??142 vs 82??73 cells/L, P?=?.012); in addition, at the 3rd and 12th month, CD4+T/month count in the early ART were significantly higher than those in later ART (57??44 vs 37??24 cells/L, P?=?.011; 18??12 vs 12??9 cells/L, P?=?.008) (Fig. ?(Fig.11C). Furthermore, after 12 months of ART, patients with CD4+T-cell counts change from baseline (CD4+T) greater than 300 cells/L, were observed in 33% of the early ART cases but K-Ras-IN-1 only 9% in those with later ART; in contrast, CD4+T less than 100 cells/L were detected in 21% of the early ART cases but almost double that number (38%) when the ART was initiated later (Fig. ?(Fig.1D1D and E). In summary, individuals with ART that had been initiated in the primary stage had K-Ras-IN-1 not only a greater CD4+T-cell count, but also a faster rate of CD4+T-cell recovery than those in whom ART started later. 3.2. Early ART restores more CD4+TN cells In addition to cell count, another important factor that contributes to CD4+T-cell functioning is the subset construction. We analyzed the CD4+T-cell subsets in patients receiving either early or later ART. By using CD45RA and CCR7, 3 CD4+T-cell subsets could be identified in human peripheral blood samples: TN, TEM, and TCM (Fig. ?(Fig.2A).2A). The percentage of CD4+TN in early ART was higher than that observed in later ART (P?=?.023), and it was similar to the situation in NC, and the percentage of CD4+TN in later ART and CHI were lower than those detected in the NC (P?=?.001; P?=?.04, respectively); in comparison with CHI, CD4+TN in PHI was higher (P?=?.036) (Fig. ?(Fig.2B).2B). The percentage of CD4+TEM K-Ras-IN-1 in CHI was higher than the corresponding values in PHI and NC (P?=?.013; P?=?.003, respectively), and the percentage of CD4+TEM in the early ART was not different from the NC; however, the percentage of CD4+TEM in later ART was higher than that in NC (P?=?.003) (Fig. ?(Fig.2D).2D). The percentage of CD4+TCM in later ART was higher than the corresponding values in CHI and NC (P?=?.003; P?=?.047, respectively) (Fig. ?(Fig.2C).2C). HIV-infected individuals receiving early ART had higher CD4+TN values and lower CD4+TEM in comparison with later ART. Open in a separate window Figure 2 Percentage of CD4+T-cell subsets and CD31+CD4+ naive T cell (TN) counts in patients receiving early antiretroviral therapy (ART) or.