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 HI V infection on lymphocyte turnover rates, we measured in a blinded study lo ngitudinal samples from 6 individuals using a highly accurate method based on two-dimensional calibration of DNA sizes. For two uninfected controls fo llowed 8 and 10 years the average telomeric terminal restriction fragment ( TRF) shortening rate in peripheral blood mononuclear cells (PBMCs) was 50 a nd 60 bp/year, respectively, in agreement with previous measurements of cro ss-sectional samples. The TRF lengths of PBMCs from two slow progressors fo llowed for 14 years declined by a rate of 120 +/- 10 bp/year, i.e. 2-fold h igher 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 shorten ed faster (240 +/- 10 bp/year) and the rate of CD4 cell TRF shortening in o ne of the fast progressors was 160 bp/year. These data suggest that HIV inf ection causes only a modest increase in the lymphocyte turnover which we sp eculate could be due to chronic activation of the immune system, and may no t result in the exhaustion of its regenerative capacity and immuno-pathogen esis.