Purpose To investigate factors involved in T-cell depletion in combination antiretroviral therapy (cART)-treated human immunodeficiency virus 1 (HIV-1)-positive patients. Patients and Methods 29 HIV-1-positive patients were enrolled. The CD4+, CD8+ T cell subsets and CD56 dim NK cells were detected by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Extraction, amplification, and viral load quantification of specimens were performed using the Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test. Results Compared with IR group, the total number of red blood cells (RBCs) and lymphocytes (LCs) in INR group was significantly reduced, and there was a significant positive correlation between the number of RBCs and that of LCs. The overall production rates of T cells-related cytokines were lower in INR group. However, the cell-surface expression of programmed death-1 (PD-1) on CD4+ T and CD8+ T cells were markedly elevated in INR group. Moreover, it was found that the proportion and the killing ability of CD56 dim NK cells significantly increased in INR patients, and significantly correlated with apoptosis of T lymphocytes. Conclusion A poor immune reconstitution in HIV-positive patients might result from multiple factors, including bone marrow suppression, high PD-1 expression on the surface of CD4+ T cells, and over-activation of T and NK cells. Besides, the activity of NK cells and RBCs count might be important auxiliary indicators for immune reconstitution and provided a reliable guidance for developing strategies to improve immune reconstitution.

Background: The replication of HIV-1 can be effectively controlled by combination antiretroviral therapy (cART) at present. However, in approximately 20% of AIDS patients with undetectable viral load under effective cART, the amount of CD4+ T cells continues to be lower than normal, showing poor immune reconstitution, which is called immune non-responder (INR). The mechanism of immune reconstitution in AIDS patients is still unclear, and thus far there is no effective improvement strategy. Aim: To investigate what factors involved in T lymphocyte depletion in INR patients.Methods: A retrospective analysis of a cohort from Suzhou Infectious Disease Hospital was performed. From October 2015 to April 2019, 29 AIDS patients, whose CD4+ T cells were less than 100/ul before treatment, were included in this study. Laboratory results were obtained from the medical records, including basic clinical information, and the results of Flow cytometer detection for CD4 T cells and ELISA for T cell-related cytokines.Results: According to the number of CD4+ T cells after 24 months of treatment, the 29 patients were divided into two groups: 15 patients with CD4+ T cells <200/ul were INR, and 14 patients with CD4+ T cells >200/ul were immune responder (IR). When Compared with IR patients, the total number of red blood cells and white blood cells, especially T lymphocytes in INR patients, was significantly lower, while programmed cell death protein 1（PD-1）on CD4+T and CD8+ T lymphocyte surface were significantly higher in INR group, which implies that the probability of T cell apoptosis was greatly increased (p<0.05). ELISA results showed that the overall production of T cell-related cytokines were lower in INR group, but the amount of cytokine secreted from each T cell was higher in INR group than that in IR group due to the significant decrease of T cell in this group. Furthermore, the proportion and the killing efficiency of CD56dim subgroup of NK cells were significantly higher in INR group. Conclusion: Multiple factors are involved in the immune reconstitution in AIDS patients, including myelosuppression, T cell destruction enhanced through PD-1 pathway, over-activation of T lymphocyte, and higher killing efficiency of CD56dim subgroup of NK cells.