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Unique Identifier : AIDSLINE MED/20146714
Rothen M; Bisset LR; Joller-Jemelka HI; Grob P; Luthy R; Opravil M; Division of Infectious Diseases and Hospital Epidemiology,; University Hospital Zurich, Switzerland.
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.
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