Increased levels of activated subsets of CD4 T cells add to the prognosticvalue of low CD4 T cell counts in a cohort of HIV-infected drug users

Objective: To identify subsets of CD4 T lymphocytes that can predict the de velopment of AIDS and to assess whether increased levels of these cellular markers could provide additional independent prognostic information to the CD4 T cell count and plasma HIV-1-RNA levels. Design and methods: In a prospective study, a cohort of 85 HIV-positive int ravenous drug users [clinical categories of the CDC classification A (n = 4 8) and B (n = 37)] were followed for a period of 37 +/- 13 months. Memory a nd activated CD4 and CD8 T cells were quantitated by three-colour flow cyto metry at baseline and expressed as a percentage of total CD4 and CD8 lympho cytes. Clinical evaluations were performed at 6 month intervals. The relati onships between these lymphocyte subsets and progression to AIDS were studi ed using Kaplan-Meier plots and proportional hazards regression models. Results: After adjustment for the level of CD4 T cells and plasma HIV-1-RNA levels, the elevation in the subset CD4+CD38+DR+ was the marker within the functionally distinct subsets of CD4 T lymphocytes with additional prognos tic value in bivariate Cox regression models. In multivariate models, incre ased percentages of CD4+CD38+DR+ T cells provided the strongest independent prognostic information for progression to AIDS (relative hazard, 1.07; P < 0.0001). Conclusion: Our results suggest that high levels of CD4+CD38+HLA- DR+ T cells reflect the increasing degree of CD4 T cell activation during t he progression of HIV infection, and could be used together with the CD4 T cell and HIV-RNA levels to evaluate more accurately the progressive cellula r immune impairment associated with the risk of progression to AIDS. (C) 20 00 Lippincott Williams & Wilkins.