Persons infected with human immunodeficiency virus (HIV) for >8 years were studied to delineate virologic and immunologic attributes of long-term survival. Whereas those with 300-700 CD4 + cells/μL often had circulating cytotoxic T lymphocytes (CTL) against HIV antigens, those with > 1000 CD4 + cells/μL did not. The subjects with > 1000 CD4 + cells/μL had low virus burden, low levels of Gag-specific CTL precursors, and minimal CD8 + cell activation. Overall, elevated levels of CD8 + cells, CD38 antigen expression on CD8 + cells, and anti-HIV functions were correlated with increased virus burden, provirus load, and HIV plasma RNA levels. A factor that suppressed HIV replication was spontaneously secreted from CD8 + cells of most subjects but not from those with high CD4 + cell counts. CD8 + cell activities, therefore, may reflect chronic viral stimulation of the immune system. Long-term survivors with high levels of CD4 + cells maintained control of viral replication but lacked the CD8 + cell activities.
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