ArticleProceedings of the National Academy of Sciences of the United States of America1995
Disparate actions of hydroxyurea in potentiation of purine and pyrimidine 2',3'-dideoxynucleoside activities against replication of human immunodeficiency virus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 72 citations in OpenAlex.
- Strategies to improve efficacy and safety of a novel class of antiviral hyper-activation-limiting therapeutic agents: the VS411 model in [corrected] HIV/AIDS.British journal of pharmacology · 2010Trial
- Effect of mycophenolate mofetil on the pharmacokinetics of antiretroviral drugs and on intracellular nucleoside triphosphate pools.Clinical pharmacokinetics · 2004Trial
- RRM2B deficiency causes dATP and dGTP depletion through enhanced degradation and slower synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Serine hydroxymethyltransferase as a potential target of antibacterial agents acting synergistically with one-carbon metabolism-related inhibitors.Communications biology · 2022Article
- Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.EMBO molecular medicine · 2020Article
- Disparate effects of cytotoxic chemotherapy on the antiviral activity of antiretroviral therapy: implications for treatments of HIV-infected cancer patients.Antiviral therapy · 2019Article
- Phospholipase D1 Couples CD4+ T Cell Activation to c-Myc-Dependent Deoxyribonucleotide Pool Expansion and HIV-1 Replication.PLoS pathogens · 2015Article
- Buffering of deoxyribonucleotide pool homeostasis by threonine metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Evidence and possible consequences of the phosphorylation of nucleoside reverse transcriptase inhibitors in human red blood cells.Antimicrobial agents and chemotherapy · 2007Article
- Quantification of the effects on viral DNA synthesis of reverse transcriptase mutations conferring human immunodeficiency virus type 1 resistance to nucleoside analogues.Journal of virology · 2005Article
- Hydroxyurea in the treatment of HIV infection: clinical efficacy and safety concerns.Drug safety · 2003Review
- In vitro hydroxyurea decreases Th1 cell-mediated immunity.Clinical and diagnostic laboratory immunology · 2001Article
- New uses for old drugs in HIV infection: the role of hydroxyurea, cyclosporin and thalidomide.Drugs · 1999Review
- Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs.Antimicrobial agents and chemotherapy · 1999Article
- Hydroxyurea enhances the activities of didanosine, 9-[2-(phosphonylmethoxy)ethyl]adenine, and 9-[2-(phosphonylmethoxy)propyl]adenine against drug-susceptible and drug-resistant human immunodeficiency virus isolates.Antimicrobial agents and chemotherapy · 1999Article
- Pharmacokinetics and pharmacodynamics of hydroxyurea.Clinical pharmacokinetics · 1998Review
- Limiting deoxynucleoside triphosphate concentrations emphasize the processivity defect of lamivudine-resistant variants of human immunodeficiency virus type 1 reverse transcriptase.Antimicrobial agents and chemotherapy · 1997Article
- Increased activation of the combination of 3'-azido-3'-deoxythymidine and 2'-deoxy-3'-thiacytidine in the presence of hydroxyurea.Antimicrobial agents and chemotherapy · 1997Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We and other groups have recently reported the potentiation by ribonucleotide reductase inhibitors such as hydroxyurea of the anti-human immunodeficiency virus type 1 (HIV-1) activity of purine and pyrimidine 2',3'-dideoxynucleosides in both resting and phytohemagglutinin-stimulated peripheral blood mononuclear cells. Little agreement prevails, however, as to the mechanism of the synergistic effects described. We report here that in phytohemagglutinin-stimulated peripheral blood mononuclear cells, two mechanisms exist for the potentiation of the anti-HIV-1 activity by low-dose hydroxyurea of the purine-based dideoxynucleoside 2',3'-dideoxyinosine and the pyrimidine-based dideoxynucleosides 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine. For 2',3'-dideoxyinosine, the enhancement arises from a specific depletion of dATP by hydroxyurea, resulting in a favorable shift of the 2',3'-dideoxyadenosine 5'-triphosphate/dATP ratio. For the pyrimidine dideoxynucleosides 3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine, the more modest anti-HIV enhancement results from hydroxyurea-induced increases of pyrimidine kinase activities in the salvage pathway and, hence, increased 5'-phosphorylation of these drugs, while depletion of the corresponding deoxynucleoside 5'-triphosphates (dTTP and dCTP) plays no significant role.
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