Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage

To define predictors of survival time in late human immunodeficiency virus type 1 (HIV-1) disease, long- and short-duration survivors were studied after their CD4(+) T cells fell to less than or equal to 50/mm(3). Immune activation of CD4(+) and CD8(+) T cells, as measured by elevated cell surface expression of CD38 antigen, was strongly associated with shorter subsequent survival (P less than or equal to.002), The naive CD45RA(+)CD62L(+) T cell reserve was low in all subjects and did not predict survival (P=.34 for CD4(+) and .08 for CD8(+) cells). Higher virus burden correlated with CD8(+) but not CD4(+) cell activation and, after correcting for multiple comparisons, was not associated with shorter survival (P=.02), All of the patients' viruses used CCR5, CXCR4, or both, and coreceptor usage did not predict survival (P=.27), Through mechanisms apparently unrelated to higher virus burden, immune activation is a major determinant of survival in advanced HIV-1 disease.