Journal Article

Rationale for the Use of Hydroxyurea as an Anti-Human Immunodeficiency Virus Drug

Franco Lori and Julianna Lisziewicz

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 30, issue Supplement_2, pages S193-S197
Published in print June 2000 | ISSN: 1058-4838
Published online June 2000 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/313851
Rationale for the Use of Hydroxyurea as an Anti-Human Immunodeficiency Virus Drug

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Hydroxyurea has been extensively used in medical practice, mainly for treating chronic myelogenous leukemia, sickle cell anemia, and other diseases. In light of its ability to inhibit DNA synthesis and to induce cell cycle arrest through inhibition of ribonucleotide reductase, the effects of hydroxyurea on replication of human immunodeficiency virus type 1 (HIV-1) have been investigated. In vitro hydroxyurea has been shown to block HIV-1 reverse transcription and/or replication in quiescent peripheral blood mononuclear cells (PBMC) and macrophages. Hydroxyurea was also found to be synergistic with the nucleoside reverse transcriptase inhibitor didanosine and to inhibit HIV-1 replication in activated PBMC; this inhibition may be due to a reduction in deoxynucleoside triphosphate pool sizes. Finally, hydroxyurea has been shown to sensitize didanosine-resistant mutants. Hydroxyurea may therefore be useful for limiting the spread of didanosine-resistant HIV-1 variants. The favorable toxicity profile of hydroxyurea and the lack of significant overlapping toxicities with some of the nucleoside reverse transcriptase inhibitors, as well as their distinct mechanisms of action, have provided further rationale for use of these agents in combination therapies.

Journal Article.  3436 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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