Immunological benefits of antiretroviral therapy in very early stages of asymptomatic chronic HIV-1 infection

Objectives: To assess whether an almost complete restoration of immune syst em can be achieved when antiretroviral therapy is initiated at very early s tages of asymptomatic chronic HIV-1 infection. Design: T cell subsets and cell-mediated responses were analysed at baselin e and after 12 months of either a double or a triple antiretroviral therapy in 26 asymptomatic HIV-1-infected patients with CD4 T cell counts > 500 x 10(6) cells/l and a baseline plasma viral load > 10 000 copies/ml. Results: Triple therapy was significantly more effective in reducing plasma HIV RNA to undetectable levels, in returning CD4:CD8 ratio to nearly norma l levels, in reducing activated cells (CD38) and in increasing naive (CD45R A(+)CD45RO(-)) and memory (CD45RA(-)CD45RO(+)) CD4 cells. Both double and t riple therapies caused a clear decrease in memory (CD45RA(-)CD45RO(+)) CD8 cells as well as a significant increase in the CD28 subset of CD8 cells. At baseline, there was an important increase in cells producing interferon-ga mma (IFN gamma) with no significant abnormalities in T lymphocytes producin g interleukin 2 (IL-2), tumour necrosis factor alpha and interleukin 4. Bot h types of therapy reduced IFN gamma- and IL2-producing CD4 T lymphocytes w hile IFN gamma-producing CD8 cells remained increased. Even before therapy, these HIV-1-positive patients lacked significant abnormalities in the T ce ll responsiveness to polyclonal stimuli as well as in the secretion of CCR5 chemokines by peripheral blood mononuclear cells. Conclusions: Initiating highly active antiretroviral therapy at very early stages of chronic HIV-1 infection allows rapid and almost complete normaliz ation of T cell subsets and preservation of T cell functions. These early-t reated patients could be excellent candidates for receiving additional HIV- specific immune-based therapies, which might be essential for the control o f HIV infection. (C) 2000 Lippincott Williams & Wilkins.