Enhancement by hydroxyurea of the anti-human immunodeficiency virus type 1 potency of 2'-beta-fluoro-2',3'-dideoxyadenosine in peripheral blood mononuclear cells.
Ribonucleotide reductase inhibitors such as hydroxyurea (HU) and related compounds, at low, non-toxic doses, enhance the anti-human immunodeficiency virus type 1 (HIV-1) potency of both purine and pyrimidine 2',3'-dideoxynucleosides (ddNs) in human lymphocytes and macrophages. The most marked enhancement of inhibition of HIV-1 replication reported to date has been seen with the purine ddN 2',3'-dideoxyinosine (ddIno): a low level of HU (0.1 mM) permitted a 4.5-fold reduction in optimal ddIno dosage with no decrease in therapeutic effect or increase in toxicity. We report here even more marked enhancement by HU of the potency of the purine ddN 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo), where the addition of 0.1 mM HU permitted a 7.1-fold reduction in the optimal dose of 2'-beta-F-ddAdo in the phytohemagglutinin-activated peripheral blood mononuclear cell HIV-1 test system.
Gao
W Y
WY
Experimental Retrovirology Section, NCI, National Institutes of Health, Bethesda, MD 20982, USA.
Mitsuya
H
H
Driscoll
J S
JS
Johns
D G
DG
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000821:virology
D000998:Antiviral Agents; D016655:HIV Core Protein p24; C073072:lodenosine; D016048:Dideoxyadenosine; D006918:Hydroxyurea