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[摘要]：Objective. Mitochondrial DNA (mtDNA) loss in peripheral blood mononuclear cells (PBMCs) has been found in both nucleoside reverse-transcriptase inhibitor (NRTI)-exposed and antiretroviral therapy (ART)- naive patients with human immunodeficiency virus (HIV) infection. Persistent immune activation might play a role in this phenomenon in HIV-infected, ART-naive patients. PBMC subsets with differential growth kinetics were therefore purified to study this similarity.Methods. CD4(+) and CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes were purified from PBMCs. mtDNA levels were quantified using real-time polymerase chain reaction and compared among the 2 groups of HIV-infected patients and a group of HIV-negative control subjects. mtDNA levels in a separate group of ART-naive patients stratified by the rate of disease progression were also evaluated with respect to their relationship to immune-activation markers (i.e., CD38 and programmed cell death - 1 [PD-1]) on CD8(+) T cells and the rate of CD4(+) T cell loss.Results. mtDNA levels in CD8(+) T cells and B cells from 15 ART-naive patients were similar to 50% less than those observed for 14 control subjects (P <=.01). mtDNA levels in all lymphocyte subsets correlated negatively with CD38(+) PD-1(+) expression (r = -0.66 to -0.9; P <=.03), and mtDNA levels in B cells correlated with the rate of CD4(+) T cell loss (r = 0.66; P <.03). In 17 HIV-infected, NRTI-exposed patients, mtDNA loss was observed in both T cell subsets (P <=.02) and was most pronounced in patients who received didanosine (P <=.002).Conclusions. In HIV-infected, ART-naive patients, mtDNA loss was found in CD8(+) T cells and B cells. These losses correlated with immune activation and, in B cells, with the rate of CD4(+) T cell loss. In patients receiving ART, only T lymphocytes had reduced mtDNA levels. This finding was probably associated with NRTI use, because it was most pronounced in patients with a history of didanosine exposure. |
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