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Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages

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), dideoxycyti...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1987
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2188703/
https://www.ncbi.nlm.nih.gov/pubmed/2821152
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description 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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spelling pubmed-21887032008-04-17 Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages J Exp Med Articles 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. The Rockefeller University Press 1987-10-01 /pmc/articles/PMC2188703/ /pubmed/2821152 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
title Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
title_full Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
title_fullStr Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
title_full_unstemmed Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
title_short Failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
title_sort failure of dideoxynucleosides to inhibit human immunodeficiency virus replication in cultured human macrophages
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2188703/
https://www.ncbi.nlm.nih.gov/pubmed/2821152