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 ≤50/mm³. 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 ≤ .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 CCRS, 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.