Primary human monocyte-derived macrophages (MDM) were shown to have diminished deoxynucleoside kinase activities compared to T lymphoblasts, and a reduced ability to phosphorylate dideoxynucleosides with anti-human immunodeficiency virus (HIV) activity. These drugs, azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyadenosine (ddA), which are potent anti-HIV agents in CD4 lymphocytes, did not inhibit HIV replication in MDM, even at concentrations of 100 microM. This drug concentration of AZT is approximately 100-fold higher than the levels attained in the serum of treated patients and the levels required to inhibit HIV replication in lymphocytes. These observations may explain the failure of AZT therapy to clear viremia, consistent with the presence of a drug-resistant reservoir of infected cells in vivo. New therapeutic approaches to inhibit the replication of HIV in MDM may be needed.
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October 01 1987
Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages.
D D Richman,
D D Richman
Department of Pathology, University of California, San Diego 92161.
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R S Kornbluth,
R S Kornbluth
Department of Pathology, University of California, San Diego 92161.
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D A Carson
D A Carson
Department of Pathology, University of California, San Diego 92161.
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D D Richman
Department of Pathology, University of California, San Diego 92161.
R S Kornbluth
Department of Pathology, University of California, San Diego 92161.
D A Carson
Department of Pathology, University of California, San Diego 92161.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1987) 166 (4): 1144–1149.
Citation
D D Richman, R S Kornbluth, D A Carson; Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages.. J Exp Med 1 October 1987; 166 (4): 1144–1149. doi: https://doi.org/10.1084/jem.166.4.1144
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