title: Improvement in immune function due to treatment with indinavir despite severe immune deficiency.
abstract: To study the virological, immunological and clinical effects of the protease inhibitor indinavir in human immunodeficiency virus (HIV)-infected patients with CD4 counts < 50 cells/mm3, indinavir was added to prior treatment with nucleoside analogues in a prospective open-label study in 23 HIV-infected patients with median CD4 count of 10 cells/mm3 and median serum HIV-1 RNA load of 27,508 copies/ml. Addition of indinavir induced a decrease in HIV-1 RNA levels to < 400 copies/ml in 15 patients that was maintained until week 36 of the study in 8 (35%) patients. The median increase in CD4 cell counts was 92 cells/mm3 (range 55-258 cells/mm3) and in CD8 counts was 245 cells/mm3 (range 51-1552 cells/mm3) at week 30. The treatment induced a significant CD8 T cell expansion, consisting in the first 6 weeks of predominantly memory CD45RO+ cells and followed by expansion of naive cells from week 12 on, and a significant decrease in the proportion of activated CD8/CD38 cells. In addition, significant increases in T cell proliferation following stimulation with phytohaemagglutinin and significant decreases in the rates of spontaneous apoptosis of CD4+ and CD8+ T cells were observed. In conclusion, the addition of indinavir induced restoration of both memory and naive CD8 T cells. Corresponding evidence of improving T cell function, as assessed by enhanced lymphoproliferative capacity and diminished propensity to undergo apoptosis, provides evidence for treatment-induced regeneration of immune function even in patients with severe immunodeficiency.
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Rothen
authors.forename: L R
authors.initials: LR
authors.lastname: Bisset
authors.forename: H I
authors.initials: HI
authors.lastname: Joller-Jemelka
authors.forename: P
authors.initials: P
authors.lastname: Grob
authors.forename: R
authors.initials: R
authors.lastname: Lüthy
authors.forename: M
authors.initials: M
authors.lastname: Opravil
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D019469:Indinavir