TY - JOUR
T1 - Anti-human immunodeficiency virus type 1 (HIV-1) CD8+ T-lymphocyte reactivity during combination antiretroviral therapy in HIV-1-infected patients with advanced immunodeficiency
AU - Rinaldo, Charles R.
AU - Huang, Xiao Li
AU - Fan, Zheng
AU - Margolick, Joseph B.
AU - Borowski, Luann
AU - Hoji, Aki
AU - Kalinyak, Christine
AU - Mcmahon, Deborah K.
AU - Riddler, Sharon A.
AU - Hildebrand, William H.
AU - Day, Richard B.
AU - Mellors, John W.
PY - 2000
Y1 - 2000
N2 - The long-term efficacy of combination antiretroviral therapy may relate to augmentation of anti-human immunodeficiency virus type 1 (HIV-1) CD8+ T- cell responses. We found that prolonged treatment of late-stage HIV-1- infected patients with a protease inhibitor and two nucleoside reverse transcriptase inhibitors failed to restore sustained, high levels of HIV-1- specific, HLA class I-restricted, cytotoxic-T-lymphocyte precursors and gamma interferon (IFN-γ) production by CD8+ T cells. In some patients, particularly those initiating three-drug combination therapy simultaneously rather than sequentially, there were early, transient increases in the frequency of anti-HIV-1 CD8+ T cells that correlated with decreases in HIV-1 RNA and increases in T-cell counts. In the other patients, HIV-1-specific T- cell functions either failed to increase or declined from baseline during triple-drug therapy, even though some of these patients showed suppression of plasma HIV-1 RNA. These effects of combination therapy were not unique to HIV-1 specific T-cell responses, since similar effects were noted for CD8+ T cells specific for the cytomegalovirus pp65 matrix protein. The level and breadth of CD8+ cell reactivity to HLA A*02 HIV-1 epitopes, as determined by IFN-γ production and HLA tetramer staining after combination therapy, were related to the corresponding responses prior to treatment. There was, however, a stable, residual population of potentially immunocompetent HIV-1- specific T cells remaining after therapy, as shown by tetramer staining of CD8+ CD45RO+ cells. These results indicate that new strategies will be needed to target residual, immunocompetent HIV-1-specific CD8+ T cells to enhance the effectiveness of antiretroviral therapy in patients with advanced immunodeficiency.
AB - The long-term efficacy of combination antiretroviral therapy may relate to augmentation of anti-human immunodeficiency virus type 1 (HIV-1) CD8+ T- cell responses. We found that prolonged treatment of late-stage HIV-1- infected patients with a protease inhibitor and two nucleoside reverse transcriptase inhibitors failed to restore sustained, high levels of HIV-1- specific, HLA class I-restricted, cytotoxic-T-lymphocyte precursors and gamma interferon (IFN-γ) production by CD8+ T cells. In some patients, particularly those initiating three-drug combination therapy simultaneously rather than sequentially, there were early, transient increases in the frequency of anti-HIV-1 CD8+ T cells that correlated with decreases in HIV-1 RNA and increases in T-cell counts. In the other patients, HIV-1-specific T- cell functions either failed to increase or declined from baseline during triple-drug therapy, even though some of these patients showed suppression of plasma HIV-1 RNA. These effects of combination therapy were not unique to HIV-1 specific T-cell responses, since similar effects were noted for CD8+ T cells specific for the cytomegalovirus pp65 matrix protein. The level and breadth of CD8+ cell reactivity to HLA A*02 HIV-1 epitopes, as determined by IFN-γ production and HLA tetramer staining after combination therapy, were related to the corresponding responses prior to treatment. There was, however, a stable, residual population of potentially immunocompetent HIV-1- specific T cells remaining after therapy, as shown by tetramer staining of CD8+ CD45RO+ cells. These results indicate that new strategies will be needed to target residual, immunocompetent HIV-1-specific CD8+ T cells to enhance the effectiveness of antiretroviral therapy in patients with advanced immunodeficiency.
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U2 - 10.1128/JVI.74.9.4127-4138.2000
DO - 10.1128/JVI.74.9.4127-4138.2000
M3 - Article
C2 - 10756025
AN - SCOPUS:0343183221
SN - 0022-538X
VL - 74
SP - 4127
EP - 4138
JO - Journal of Virology
JF - Journal of Virology
IS - 9
ER -