Effect of didanosine, stavudine, and hydroxyurea therapy on apoptosis in CD45RA(+) and CD45RO(+) T lymphocyte subpopulations

The effect of aggressive antiretroviral therapy on spontaneous apoptosis (A P) in CD4(+) and CD8(+) lymphocytes expressing CD45RO (memory cells) and CD 45RA (naive cells) and their relationship to cellular activation and viral load were examined. Ten patients receiving simultaneous treatment with d4T, ddI, and HU were evaluated. Flow cytometric analysis showed significant le vels of AP (measured by TUNEL assay) among memory and naive T cells and an enhanced expression of CD38 and HLA-DR activation markers. The percentage o f apoptotic CD4(+)CD45RO(+) and CD4(+)CD45RA(+) cells decreased, respective ly, from 34 +/- 3.3 and 29 +/- 3.6 prior to treatment to 20.5 +/- 4 and 22 +/- 3.8 at week 8 into therapy. The percentage of apoptotic CD8(+)CD45RO(+) and CD8(+)CD45RA(+) cells similarly decreased, respectively, from 20 +/- 2 .5 and 24 +/- 3 prior to treatment to 14.5 +/- 2.7 and 16 +/- 3 at week 8 i nto treatment. The percentage of CD4(+) cells expressing the activation mar kers CD38 and HLA-DR decreased from 27 +/- 6 to 13 +/- 2 and from 26 +/- 4 to 13.5 +/- 3, respectively. The percentage of CD8(+) cells expressing eith er CD38 or HLA-DR fell from 22 +/- 3 to 10 +/- 2 for the former and from 39 +/- 5 to 22 +/- 4 for the latter. This was associated with a significant d ecrease in viral load (mean, 1.4 log(10)), and a decline in circulating pla sma TNF-alpha and sIL-2R levels from 50.5 +/- 10 to 21 +/- 6 and 92.5 +/- 1 1 to 68 +/- 9, respectively. These data indicate that short-term therapy wi th ddI, d4T, and HU in combination diminished AP, immune activation, and pa rtially restored naive and memory T cell subpopulations.