Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-HIV CD8+ lymphocyte activity

Abstract

Persons infected with human immunodeficincy virus (HIV) for > 8 years were studied to delinate virologic and immunologic attributes of long- term survival. Whereas those with 300-700 CD4+ cell/mL often had circulating cytotoxic T lymphocytes (CTL) agaist HIV antigens, those with > 1000 CD4+ cells/mL did not. The subjects with > 1000 CD4+ cells/mL 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 supressed HIV replication was spontaneously secrected from Cd8+ cells of most subjects but not from those with high CD 4+ cell counts. CD8+ cell activities, therefore, may reflect chronic viral stimulation of the immune system. Long-term survivors with high level of CD4+ cells maintained control of viral replication but lacked the CD8 + cell activation.