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

Abstract

OBJECTIVES: 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. DESIGN: 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 x 10(6) cells/l and a baseline plasma viral load > 10000 copies/ml. RESULTS: 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-gamma (IFNgamma) with no significant abnormalities in T lymphocytes producing interleukin 2 (IL-2), tumour necrosis factor alpha and interleukin 4. Both types of therapy reduced IFNgamma- and IL2-producing CD4 T lymphocytes while IFNgamma-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. CONCLUSIONS: 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.