AIDSWEEKLY Plus; Monday, December 21, 1998
Daniel J. DeNoon, Senior Editor
The drugs are the cornerstones of most highly active antiretroviral therapy (HAART) regimens. Recent studies seemed to predict trouble: they showed that PIs interact with the multidrug resistance protein MDR1 (also known as P-glycoprotein or Pgp) (Kim, R.B. et al., J Clin Invest, 1998;101:289-94; Lee, C.G.L. et al., Biochemistry, 1998;37:3594-601). The protein is a member of the ABC family of transporter proteins, which determine resistance to various chemotherapeutic agents used in cancer treatment.
But now Ranga V. Srinivas and colleagues of St. Jude Children's Research Hospital, Memphis, Tennessee, show that this interaction appears to inhibit the activity of MDR1 and the associated multiple- drug-resistance-associated protein MRP1 in T cells.
"HIV PIs were equally effective against HIV in both wild-type and multidrug-resistant T-lymphocytic cell lines, suggesting that cellular resistance to HIV PIs via activation of an ABC-type drug transporter protein may not be a major therapeutic concern," they concluded.
Srinivas et al. reported their findings in the journal Antimicrobial Agents and Chemotherapy ("Human Immunodeficiency Virus Protease Inhibitors Serve as Substrates for Multidrug Transporter Proteins MDR1 and MRP1 But Retain Antiviral Efficacy in Cell Lines Expressing These Transporters," Antimic Ag Chem, 1998;42(12):3157-62).
However, the authors noted that viral resistance to PIs accounts for up to a half of treatment failures. Because of the importance physiologic mechanisms appear to play in this process, they want to be sure their preliminary findings are accurate.
"We are currently investigating whether activation of multidrug transporters plays any role in failure of PI therapy," they wrote.
This work was supported by U.S. Public Health Service grants, by a Cancer Center (CORE) grant from the NIH, and by the American Lebanese Syrian Associated Charities.
The corresponding author for this study is Ranga V. Srinivas, Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, Tennessee 38105. Phone: (901) 495-2359. Fax: (901) 495-3099. Email: <ranga.srinivas@stjude.org>.
981221
AW981212
Copyright © 1998 - 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.newsfile.com
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 1998. 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, 1998. 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. .