Decline in total T cell count is associated with onset of AIDS, independent of CD4⁺ lymphocyte count: Implications for AIDS pathogenesis

We previously reported that blind T cell homeostasis, in which the total T cell count is maintained but the CD4⁺ and CD8⁺ subset composition of the T cells can vary, fails approximately 1.5 to 2.5 years before the onset of AIDS. The present study was premised on the hypothesis that if failure of T cell homeostasis (i.e., a decline in total T cell counts) is important in the pathogenesis of AIDS, it should be a significant predictor of AIDS after controlling for the CD4⁺ lymphocyte count. Data from 1556 homosexual men with sufficient sequential T cell subset measurements were evaluated, representing 11,988 person-visits in men with known clinical outcomes over a period of more than 10 years. Using regression models that incorporated CD4⁺ lymphocyte count and HIV-related symptoms (fever, thrush), it was determined that a yearly decline of more than 300 T cells/μl of peripheral blood was an independent predictor of the onset of AIDS for subjects with CD4⁺ lymphocyte counts of <500 cells/μl. The results support an important role for failure of T cell homeostasis in the pathogenesis of AIDS.