title: 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 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/microL often had circulating cytotoxic T lymphocytes (CTL) against HIV antigens, those with > 1000 CD4+ cells/microL did not. The subjects with > 1000 CD4+ cells/microL 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.
authors.affiliation: Department of Medicine, School of Medicine, University of California at Los Angeles, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ferbas
authors.forename: A H
authors.initials: AH
authors.lastname: Kaplan
authors.forename: M A
authors.initials: MA
authors.lastname: Hausner
authors.forename: L E
authors.initials: LE
authors.lastname: Hultin
authors.forename: J L
authors.initials: JL
authors.lastname: Matud
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: D L
authors.initials: DL
authors.lastname: Panicali
authors.forename: H
authors.initials: H
authors.lastname: Nerng-Ho
authors.forename: R
authors.initials: R
authors.lastname: Detels
authors.forename: J V
authors.initials: JV
authors.lastname: Giorgi
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000032:analysis; D005500:Follow-Up Studies; D006678:HIV / Q000302:isolation & purification*; D006679:HIV Seropositivity / Q000276:immunology / Q000821:virology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis; D012367:RNA, Viral / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015996:Survival Rate; D017741:Survivors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014762:Viral Interference / Q000276:immunology; D014776:Virus Cultivation; D014779:Virus Replication / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D000943:Antigens, Differentiation; C067361:CD8 receptor; D004279:DNA, Viral; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1