Long-term telomere dynamics: Modest increase of cell turnover in HIV-infected individuals followed for up to 14 years

To quantify the long-term dynamics of telomere lengths and the effect of HIV infection on lymphocyte turnover rates, we measured in a blinded study longitudinal samples from 6 individuals using a highly accurate method based on two-dimensional calibration of DNA sizes. For two uninfected controls followed 8 and 10 years the average telomeric terminal restriction fragment (TRF) shortening rate in peripheral blood mononuclear cells (PBMCs) was 50 and 60 bp/year, respectively, in agreement with previous measurements of cross-sectional samples. The TRF lengths of PBMCs from two slow progressors followed for 14 years declined by a rate of 120 +/- 10 bp/year, i.e. 2-fold higher than the rate of TRF shortening for uninfected individuals. The rate of TRF shortening was higher in CD8 (140 +/- 10 bp/year) than in CD4 (100 +/- 10 bp/year) cells. The CD8 cell TRFs of the two fast progressors shortened faster (240 +/- 10 bp/year) and the rate of CD4 cell TRF shortening in one of the fast progressors was 160 bp/year. These data suggest that HIV infection causes only a modest increase in the lymphocyte turnover which we speculate could be due to chronic activation of the immune system, and may not result in the exhaustion of its regenerative capacity and immuno-pathogenesis.