AIDSWEEKLY Plus; Monday, December 14, 1998
Daniel J. DeNoon, Senior Editor
Recent studies have shown that efavirenz, recently approved, has extraordinarily potent anti-HIV activity. Efavirenz is a member of the highly specific non-nucleoside reverse transcriptase inhibitors (NNRTIs). Its potency holds promise that when used in combination with nucleoside-based inhibitors (NRTIs) it can allow patients the option of saving HIV protease inhibitors for second-line treatment.
Moreover, laboratory studies suggested that efavirenz might be active against HIV strains that had developed resistance to other NNRTIs, including the already-approved delavirdine and nevirapine.
Now clinical evidence suggests that NNRTI cross resistance may be of greater importance than had been hoped. Veronica Miller of Goethe University and colleagues explored NNRTI cross resistance in clinical samples obtained from patients treated over time with the novel NNRTI loviride (a member of the (alpha)-anilinophenylacetamide or (alpha)- APA group).
"Our data indicate that the available newer NNRTIs which retain activity against some HIV-1 strains selected by other compounds of this class in vitro may have compromised clinical efficacy in some patients pretreated with NNRTIs," Miller et al. found.
The researchers reported their findings in the journal Antimicrobial Agents and Chemotherapy ("Patterns of Resistance and Cross-Resistance to Human Immunodeficiency Virus Type 1 Reverse Transcriptase Inhibitors in Patients Treated with the Nonnucleoside Reverse Transcriptase Inhibitor Loviride," Antimic Ag Chem, 1998;42(12):3123-9).
Miller et al. tested for cross reactivity to nevirapine, delavirdine, efavirenz (a benzoxazin-2-one derivative), HBY-097 (a quinoxaline compound), and tivirapine (one of the 8-C1-TIBO derivatives).
The degree of loviride cross resistance to all of the NNRTIs tested was extinsime. However, loviride cross resistance to efavirenz was significantly less than that seen with nevirapine.
Unfortunately, phenotypic cross resistance could not be predicted from a genotypic search for known NNRTI resistance mutations.
"If NNRTI resistance exists due to prior NNRTI treatment failure, the options for subsequent treatment with this class of drugs may be severely limited," Miller et al. wrote. "Future research with this class of compounds should include the development of compounds selected for activity against NNRTI-resistant HIV-1 and the clinical testing of NNRTI combinations."
This work was supported by a grant from the Janssen Research Foundation.
The corresponding author for this study is Veronica Miller, Klinikum der J.W. Goethe Universitat, Zentrum der Inneren Medizin, Infektionsambulanz, Haus 68, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. Phone: (49) 69-6301-7680. Fax: (49) 69-6301-5712. Email: <miller@em.uni-frankfurt.de>.
981214
AW981209
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. .