Anti-retroviral therapy in HIV-infected patients: in vitro effects of AZT and saquinavir on the response of CD4 and CD8 lymphocytes to interleukin-7

IL-7 is a crucial cytokine regulating lymphopoiesis and peripheral T lymphocyte homeostasis. Plasma IL-7 levels increase during HIV infection and, although antiretroviral therapy (ARV therapy) decreases these levels, they fail to return to normal. Immune reconstitution in most ARV-treated patients is only partial. We tested the possibility that the IL-7R system might be affected by ARV drugs. The effects of the antireverse transcriptase AZT and the anti-protease saquinavir on CD3- and CD3+CD28-induced T lymphocyte stimulation, in the presence (or absence) of IL-7, were studied in vitro. Small amounts of the drugs did not interfere with the capacity of IL-7 to stimulate T cell proliferation, but higher concentrations significantly decreased IL-7-induced T cell proliferation both in cells from HIV-infected patients and in cells from healthy donors. IL-7 is known to down-modulate its own receptor on the surface of CD4 and CD8 T lymphocytes in vitro. In CD4 lymphocytes from healthy donors or HIV-infected patients, neither AZT, nor saquinavir, nor a combination of the two, interfered with this property. In contrast, AZT + saquinavir worsened the IL-7-induced down-regulation of CD127 expression by CD8 T cells from HIV-infected patients, while no such effect was observed with CD8 T cells from healthy donors. Our data suggest that, under certain conditions, antiretroviral therapy could interfere with the expression and function of the IL-7/IL-7R system, and more particularly it may affect the CD8-lymphocyte compartment of HIV-infected patients.