AIDSWEEKLY Plus; Monday, December 30, 2002
Michael Greer, Senior Medical Writer

"Recently, the use of the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) in combination with nucleoside analogs has gained attention as a potential strategy for anti-HIV-1 therapy," explained Christopher N. Mayhew and colleagues at the University of Kentucky in Lexington, the University of Wolverhampton in the United Kingdom, the University of the North in Sovenga, South Africa, and Richmond, Virginia-based Molecules for Health, Inc. "However, appeal for the long-term use of HU in HIV-1 infection may be limited by its propensity to induce hematopoietic toxicity."

Mayhew and coauthors identified two RR inhibitors with antiviral efficacy comparable to that of hydroxyurea, but without HU's adverse hematological effects.

The researchers evaluated the safety and effectiveness of the RR inhibitors didox (DX) and trimidox (TX) in a murine model of AIDS. In addition to suppressing RR activity, both of these agents act as free-radical scavengers, they noted.

DX and TX, like HU, suppressed the progression of retroviral disease in mice. Unlike HU, however, neither DX nor TX were associated with toxicity to hematopoietic cells, study data showed.

Eventually, HU-treated animals invariably died from HU-related hematopoietic progenitor cell damage (Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox - Novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea. Antiviral Res 2002 Nov;56(2):167-81.

"These results suggest that due to their reduced hematopoietic toxicity and ability to inhibit disease progression in murine AIDS, TX and DX may offer effective alternatives to HU therapy in HIV-1 infection," Mayhew and colleagues concluded.

The corresponding author for this report is Vincent S. Gallicchio, Department of Clinical Sciences, University of Kentucky Medical Center, CHS Building, 900 South Limestone Street, Lexington, KY 40536 USA. E-mail: vsgall1@uky.edu.

A search at www.NewsRx.net using the search term "AIDS and HIV therapy" yielded 1193 articles in 29 specialized reports.

Key points reported in this study include:

• A pair of novel agents may represent promising hydroxyurea (HU) alternatives for HIV patients

• The ribonucleotide reductase (RR) inhibitor HU significantly slows progression to AIDS, but can also cause life-threatening hematopoietic damage

• The RR inhibitors didox and trimidox provide the same benefits as HU with little or no toxicity

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference:

Mayhew CN, Mampuru LJ, Chendil D, et al., "Suppression of retrovirus-induced immunodeficiency disease (murine AIDS) by trimidox and didox: novel ribonucleotide reductase inhibitors with less bone marrow toxicity than hydroxyurea", Antiviral Res 2002 Nov;56(2):167-81

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