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

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Abstract
To 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. T 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. Triple 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. Initiating 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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