T-cell receptor excisional circles, telomere length, proliferation and apoptosis in peripheral blood mononuclear cells of human immunodeficiency virus-infected individuals after 18 months of treatment induced viral suppression.

This study evaluated the effect of highly active antiretroviral therapy (HAART)-induced viral suppression on T-cell receptor excisional circles (TRECs), telomere length, proliferative responses and spontaneous as well as phytohaemagglutinin (PHA)-stimulated lymphocyte apoptosis in 27 human immunodeficiency virus (HIV)-infected individuals followed for 18 months during HAART. Our results show that HAART significantly increased the level of TRECs in CD4+ cells (P = 0.003) after 18 months of almost continuously suppressed HIV-RNA levels. Lymphocyte proliferative responses and apoptosis levels in patients were significantly lower and significantly higher, respectively, compared with healthy controls. The proliferative response and apoptosis levels did not change during follow up. Changes in telomere length were observed in CD4+ and in CD8+ T cells. The study demonstrated that HAART induces normal TREC levels in the CD4+ T-cell pool. However, the other perturbed functions in T cells indicate that immune reconstitution is incomplete and may need longer viral suppression.

Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts.

Hematologic and immunologic functions were examined in 19 HIV-negative infants of HIV-positive mothers and 19 control infants of HIV-negative mothers. Control infants were selected to match for gestational age, weight, and mode of delivery. Cord blood was obtained from all infants and used for flow cytometric determination of lymphocyte subsets, including the naive CD4 count. Furthermore, to determine thymic output, cord blood mononuclear cells were used for determination of T-cell receptor excision circles (TRECs). Evaluation of progenitor cell function was done by means of colony-forming cell assay and fetal thymic organ cultures (FTOCs). Lower naive CD4 counts (459.3 +/- 68.9 vs 1128.9 +/- 146.8 cells/microL, P <.001) and reduced thymic output in infants of HIV-positive mothers were found (frequency of CD4(+) cells with TRECs was 3.6% +/- 0.7% compared with 14.3% +/- 2.2% in controls, P <.001). In combination with lower red blood cell counts in infants of HIV-positive mothers, this finding suggested impairment of progenitor cell function. Indeed, progenitors from infants of HIV-positive mothers had decreased cloning efficiency (15.7% +/- 2.6% vs 55.8% +/- 15.9%, P =.009) and seemed to generate fewer T cells in FTOCs. In conclusion, lower numbers of naive CD4(+) cells and reduced thymic output in HIV-negative infants of HIV-positive mothers may be due to impaired progenitor cell function.