Abnormal Activation of T Cells in HIV-1 Infection After Antiretroviral Therapy

  Objective   To investigate the relationship between abnormal activation of T cell subsets in peripheral whole blood and the recovery of immune function in persons infected with HIV-1, and to examine the relationship between the size of the viral reservoir of HIV-1 DNA and T cell subsets.

  Methods   HIV-1-infected persons who underwent routine testing between July 2019 and May 2020 were the target population of the study. According to whether, at the time of enrollment, their CD4⁺ T cells reached 500 cells/μL after antiretroviral therapy (ART), HIV-1-infected persons were divided into two groups, 76 in the deficiency group and 61 in the immune recovery group. In addition, 22 people who were not exposed to HIV-1, and who were tested negative for HIV-1 antibody were selected as the control group. For the three groups of subjects, tests of the T cell subsets were conducted. A total of 77 HIV-1-infected persons, with 44 from the deficiency group and 33 from the recovery group, were examined for HIV-1 DNA reservoir. The deficiency group and the recovery group were followed up 6 months later and the CD4⁺ T cell test results of 133 blood samples were collected, with 74 from the deficiency group and 59 from the recovery group.

  Results   The proportions of activated CD4⁺ and CD8⁺ T cells of the deficiency group were higher than those of the recovery group and the control group. The proportions of senescent CD4⁺ and CD8⁺ T cells in the deficiency group were comparable to those of the recovery group, which were higher than those of the control group, showing significant differences only in senescent CD8⁺ T cells, and no significant difference in senescent CD4⁺ T cells. The deficiency group expressed higher levels of effector memory CD4⁺ T and CD8⁺ T cells than the control group did, and the recovery group only expressed a higher level of effect memory CD8⁺ T cells. Both the deficiency group and the recovery group showed lower levels of central memory CD4⁺ T and CD8⁺ T cells than the control group did, and the recovery group had an even lower level of central memory CD4⁺ T cells than the deficiency group did. The recovery group showed a higher expression level of naïve CD4⁺ T cells, and the deficiency group and the recovery group had lower expression levels of naïve CD8⁺ T cells than the control group did. There was no correlation between the size of the viral reservoir of HIV-1 DNA and CD4⁺ T cell count or the T cell subsets. Activated CD4⁺ T cells, activated CD8⁺ T cells, and central memory CD4⁺ T cells were negatively correlated with the follow-up findings for CD4⁺ T cells, with r at −0.378, −0.334, and −0.322, respectively (P<0.05). Naïve CD4⁺ T cells and naïve CD8⁺ T cells were positively correlated with the follow-up findings for CD4⁺ T cell subset, with r at 0.350 and 0.267, respectively (P<0.05).

  Conclusion  HIV-1 infected persons have varying degrees of abnormal immune activation of T cell subsets. The abnormal activation of some T-cell subsets is partly associated with the subsequent recovery of immune functions and the size of the viral reservoir of HIV-1 DNA was not associated with the T cell subsets.