Increases in T cell telomere length in HIV infection after antiretroviral combination therapy for HIV-1 infection implicate distinct population dynamics in CD4(+) and CD8(+) T cells

Changes in mean telomeric terminal restriction fragment (TRF) length were e xamined as a marker for cellular replicative history in HIV-1-infected indi viduals after institution of anti-retroviral therapy (ART). Increases in me an T cell TRF lengths were observed in most patients following therapy; how ever, the contribution of individual T cell subsets was complex. An elongat ion of CD8(+) T cell TRF was nearly uniformly observed while changes in mea n TRF length in CD4(+) T cells were heterogeneous as, despite potent suppre ssion of viral replication, CD4 cell telomeres recovered in some patients, yet continued to decline in others. Increases in CD8 cell TRF correlated wi th decreased memory cells, suggesting a negative selection in the periphery for CD8 cells with extensive replicative history. In contrast, increases i n CD4(+) T cell TRF length correlated with increases in naive cell subsets, suggesting that the CD4(+) T cell TRF increase may reflect a thymic contri bution in some patients. These are the first increases in somatic cell telo mere length in a population of cells observed in vivo, and the findings are compatible with therapy-induced reconstitution of the lymphoid compartment with cells having a more extensive replicative potential. These findings f urther distinguish lymphocytes from other somatic cell populations where on ly decreases in TRF over time have been noted. Thus, institution of ART in persons with moderately advanced HIV-1 disease reveals distinct population dynamics of CD4 and CD8 T cell subsets and also shows that the lymphocyte r eplicative history is dynamic. (C) 1999 Academic Press.