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

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ObjectivesTo assess whether an almost complete restoration of immune system can be achieved when antiretroviral therapy is initiated at very early stages of asymptomatic chronic HIV-1 infection.DesignT cell subsets and cell-mediated responses were analysed at baseline 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 × 106 cells/l and a baseline plasma viral load > 10 000 copies/ml.ResultsTriple therapy was significantly more effective in reducing plasma HIV RNA to undetectable levels, in returning CD4:CD8 ratio to nearly normal levels, in reducing activated cells (CD38) and in increasing naive (CD45RA+CD45RO−−) and memory (CD45RA−−CD45RO+) CD4 cells. Both double and triple 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-γ (IFNγ) with no significant abnormalities in T lymphocytes producing interleukin 2 (IL-2), tumour necrosis factor α and interleukin 4. Both types of therapy reduced IFNγ- and IL2-producing CD4 T lymphocytes while IFNγ-producing CD8 cells remained increased. Even before therapy, these HIV-1-positive patients lacked significant abnormalities in the T cell responsiveness to polyclonal stimuli as well as in the secretion of CCR5 chemokines by peripheral blood mononuclear cells.ConclusionsInitiating highly active antiretroviral therapy at very early stages of chronic HIV-1 infection allows rapid and almost complete normalization of T cell subsets and preservation of T cell functions. These early-treated patients could be excellent candidates for receiving additional HIV-specific immune-based therapies, which might be essential for the control of HIV infection.

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