The pattern and magnitude of T cell subsets reconstitution during ten years of ART with viral suppression in HIV-infected patients

Abstract

Background: The extent of immune reconstitution in human immunodeficiency virus (HIV) infected persons receiving long-term antiretroviral therapy (ART) with controlled viral load has been controversial. We studied the extent and speed of T cell subsets retrieval after long-term antiretroviral treatment.

Methods: 662 HIV-infected patients followed at least 2 years whose plasma HIV-1 RNA load <50 copies/mL were evaluated for longitudinal and functional phenotypic indices of immune restoration. Determinants of change in magnitude and importance of recovery have been evaluated using mixed linear regression models.

Results: Almost all robust immune restorations achieved occurred after 2-3 years of ART. The median CD4 lymphocyte count increased 449 cells/μl (IQR 303-604) from 226 cells/μl (IQR 83-336) at baseline during the third year (P < 0.001); CD4+T lymphocyte rises during the sixth and tenth years were not significant. Naive and memory CD4+T cells'reconstitution occurred in the sixth and eighth years of ART but no significant change thereafter. The change of CD45RA+Naïve and CD45RA-memory CD4+T cell reconstitution is different in baseline CD4+T cell counts <100 cells/μl group and in baseline CD4+T cell counts >100 cells/μl group. Activation antigen expression (CD38 or HLA-DR) on CD8 lymphocytes declined mostly during the first till second year, and after 4 years, activation antigen expression on patient lymphocytes showed no significant change. The proportion of CD4 cells expressing CD28 climbed during the first years and reached normal levels in the second year.

Conclusions: Immune restoration was dependent on the capacity of immune system during the first 2-3 year of ART. But the significant change of CD4 and compartments of CD4+T cells could persist until 6-8 years. The pattern of CD38+CD8+, HLA-DR+CD8+, CD28+CD4+ T cells could quickly return to normal level and no significant change after sufficient time of ART. In general, the immune response compared to the baseline status may be the overall effect from the age and time of antiretroviral treatment.

Keywords: CD4+T cell; CD4/CD8; HIV; T cell subsets; antiretroviral treatment; immune reconstitution.

Figure 1

Fitted curve of estimated trends and calculated mean with SD of the count CD4+T cell (A), CD8+T cell (B), CD4/CD8 (C), Memory CD4+T cell (D) and Naïve CD4+T cell (E). Notes: predicted value means the predicted indicators calculated by the mixed linear model used in the article, upper CI and lower CI means the upper confidence interval and lower confidence interval of predicted value. Actual value and SD were calculated from original data. The green shade represented a significant change during 2–3 year interval, the pink shade represented no significant change during that time.

Figure 2

The trends of naïve/memory T cell change after 10-year of ART stratified by baseline CD4+T cells. Notes: Different color represents different level of baseline CD4+T cell counts, which shown in top right corner.