INCREASED NUMBERS OF PRIMED ACTIVATED CD8-CELLS PREDICT THE DECLINE OF CD4+ T-CELLS IN HIV-1-INFECTED PATIENTS(CD38+CD45RO+ T)

Objective: To look for surrogate markers in HIV-1 infection that can p redict the decline of CD4+ T cells. Methods: Multiparameter flow cytom etric analyses of CD8+ lymphocytes were performed. These cells were in vestigated for their expression of the activation marker CD38+ within the naive (CD45RA+) and primed (CD45RO+) subsets. Serial CD4 counts we re plotted for each patient and the straight line that best fitted was obtained using least squares regression. Differences in rate of decli ne were tested using analysis sis of variance, after each patient was weighted by the reciprocal of the variance. Results: Baseline levels o f percentages of CD8+CD38+ T lymphocytes predict the CD4 decline in HI V-1-infected patients. Within the CD8+ subset, the primed CD8+CD38+CD4 5RO+ population was responsible for this prediction. Conversely, the n aive CD8+CD38+CD45RA+ population was not predictive. Patients who init ially showed a percentage of CD8+CD38+ T lymphocytes above the median (> 25%) had a more marked decline in CD4+ T cells when compared to ind ividuals with percentages of CD8+CD38+ T lymphocytes below the median value (79.3 and 21.2x10(6)/l mean CD4 cell decline per year, respectiv ely). Similarly, percentages of CD8+CD38+CD45RO+ T cells above the med ian value (> 7%) were also associated with a more rapid decline (69.4 and 14.2x10(6)/l mean CD4+ cell decline per year). These results were statistically significant after adjustment for the baseline CD4 count and beta(2)-microglobulin levels. Conclusions: Percentages of activate d CD8+ cells expressing CD38+ can predict the rate of decline (slope) of the CD4+ T cells. This resides in the CD45RO+ primed population. An early prediction of the CD4+ slope will allow the clinician to target treatment to those patients that are most likely to benefit.