Changes in levels of T cell subpopulations to monitor the response to antiretroviral therapy among HIV-1-infected patients during two years of HIV-1 replication suppression

摘要

Objectives: The aim of this study was to compare the effect of 2 y of antiretroviral therapy (ART) on the percentage of activated CD38(+)CD8(+) T cells and human leukocyte antigen (HLA)-DR(+)CD8(+) T cells, and the expression of the co-stimulatory molecule CD28 on CD4(+) and CD8(+) T cells in the peripheral blood of HIV-infected adults, and to assess the use of immune activation markers to predict the virological response to ART in a cohort of HIV-1-infected patients in the north-western part of China. Methods: We analyzed changes in the CD4(+) T cell count, viral load, and the percentages of CD38(+)CD8(+) T cells, HLA-DR(+)CD8(+) T cells, CD28(+)CD4(+) T cells, and CD28(+)CD8(+) T cells in 48 patients with HIV diseases during 2 y of suppressive highly active antiretroviral therapy (HAART). Good virological responders (n = 20) were defined as those who had suppressed and maintained a plasma viral load below the detection limit of the assay for at least 12 months. Poor virological responders (n = 28) were defined as those with a detectable viral load at 6 and 12 months after beginning HAART. Results: Among the 20 good responders, baseline median levels of CD38(+)CD8(+) T cells were elevated, but had decreased significantly at 24 months of therapy (p < 0.0001). Median levels of HLA-DR(+)CD8(+) T cells also decreased at 24 months of therapy (p < 0.0001). Levels of expression of CD28(+)CD4(+) T cells rose steadily to 6 months (p = 0.03), and smoothly reached levels observed among HIV-negative blood donors during the 24 months of therapy (p > 0.05). Levels of expression of CD28(+)CD8(+) T cells increased at 24 months (p = 0.04). Among the 28 poor responders, median levels of CD38(+)CD8(+) T cells decreased significantly at 24 months (p < 0.0001). Levels of HLA-DR(+)CD8(+) T cells also decreased at 24 months (p < 0.001). Levels of CD28(+)CD8(+) T cells and levels of CD28(+)CD4(+) T cells increased at 24 months remained unchanged. The percentage of CD38(+)CD8(+) T cells appeared to provide a sensitive estimate of the overall immune recovery in comparison with the percentage of HLA-DR(+)CD8(+) T cells, although this lacked specificity for the determination of early virological drug failure and did not appear to be a reliable surrogate for RNA viral load. Conclusions: We show that HAART can be used successfully in Chinese populations with elevated baseline immune activation markers and that the percentage of CD38(+)CD8(+) T cells may be an additional parameter to the current criteria for estimating the antiretroviral response with HAART.