Important note: Information in this article was accurate in August 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, August 30, 1999
Daniel J. DeNoon, Senior Editor
CW HENDERSON PUBLISHER -- Hydroxyurea (HU) increases the action of other anti-HIV drugs - even against viral strains resistant to those drugs, a new study suggests.
HU, an anticancer agent of long standing, inhibits the cellular enzyme ribonucleotide reductase and leads to reduced pools of deoxynucleotide triphosphates (dNTPs). Reduced pools of dNTPs favor HIV uptake of nucleoside analog inhibitors of HIV reverse transcriptase.
As the most pronounced reduction of dNTP is among deoxyadenosine triphosphates (dATPs), Stanford researchers Sarah Palmer and colleagues explored the synergy between HU and three adenosine-based nucleoside-analog reverse transcriptase inhibitors (NARTIs): didanosine (the already approved ddI or 2'-3'-dideoxyinosine); PMEA (9-[2- (phosphonylmethoxy)ethyl]adenine); and PMPA ((9-[2- (phosphonylmethoxy)propyl]adenine).
They found that HU not only increased the drugs' anti-HIV activity, but that it increased the activity of ddI and PMEA against ddI- and PMEA-resistant HIV mutants.
"This study provides evidence that supports the need for clinical trials with HU (i) in combination with ddI against ddI-resistant patient isolates and (ii) in combination with two recently developed adenosine analogs, PMEA and PMPA," Palmer et al. wrote.
Palmer et al. reported their findings in the journal Antimicrobial Agents and Chemotherapy ("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," Antimic Ag Chem, 1999;43(8):2046-50).
Didanosine and HU are manufactured by Bristol Myers Squibb, while the as-yet-unapproved PMEA and PMPA are manufactured by Gilead Sciences, Foster City, California.
The corresponding author for this study is Sarah Palmer, whose current address is: Southern Research Institute/Serquest, Department of Infectious Disease Research, 431 Aviation Way, Frederick, MD 21701-4756. Phone: (301) 694- 3232. Fax: (301) 694-7223. Email: <palmer@SRI.org>.
990830
AW990807
Copyright © 1999 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA. Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588 http://www.newsrx.net
AEGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 1999. This material is designed to support, not replace, the relationship that exists between you and your doctor.
AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2000. AEGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ĘGIS, or the party credited as the provider of the content.