Important note: Information in this article was accurate in August 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; August 5, 2002
Michael Greer, Senior Medical Writer
"Removal of nucleoside chain terminator inhibitors mediated by human immunodeficiency virus (HIV) reverse transcriptase (RT) using ATP as an acceptor molecule has been proposed as a novel mechanism of HIV resistance," according to Lisa K. Naeger and colleagues at Gilead Sciences, Inc., in Foster City, California.
Mutant RT is indeed capable of extruding nucleoside RT inhibitors in the presence of ATP although the practical effects are marginal against most agents, the researchers found.
Naeger and coauthors assessed the ability of HIV RT to remove eight different nucleoside analogs, including zidovudine (AZT), lamivudine (3TC), and didanosine (ddI). Both wild-type RT and mutant forms of the enzyme with thymidine analog resistance were evaluated, they said.
Significant removal of the thymidine analogs AZT and stavudine (d4T) by mutant RT were seen in the presence of ATP, study data showed. Resistant RT also demonstrated a limited ATP-dependent ability to extrude zalcitabine (ddC), abacavir, amdoxovir (DAPD), 3TC, ddI, and tenofovir.
ATP-mediated efflux of ddC, d4T, DAPD was inhibited by complementary deoxynucleoside triphosphate, although removal of other agents was unaffected (ATP-dependent removal of nucleoside reverse transcriptase inhibitors by human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 2002 Jul;46(7):2179-84.
"Thymidine analogs AZT and d4T were the most significantly removed by the mutant enzyme, suggesting that removal of these inhibitors by the ATP-dependent removal mechanism contributes to the AZT and d4T resistance observed in patients with HIV expressing thymidine analog resistance mutations," Naeger and colleagues concluded.
The corresponding author for this report is Michael D. Miller, 333 Lakeside Dr., Foster City, CA 94404, USA. E-mail: michael_miller@gilead.com.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
020805
AW020802
Copyright © 2002 - 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 2002. 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 © 1980,2002. AEGiS. 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 AEGiS, or the party credited as the provider of the content.