Second International Congress Drug Therapy in HIV Infection 18-22 November 1994 Glasgow, UK

HIV DRUG RESISTANCE

Douglas D. Richman
Departments of Pathology and Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0679, USA

Int Cong Drug Therapy HIV 1994 Nov 18-22;2:Abstract No. 3.2
AIDS 1994, Vol. 8 (Suppl. 4);S3

Diminished susceptibility of HIV to antiretroviral drugs and the appearance of corresponding mutations are being extensively documented. The significance of the emergence of diminished drug susceptibility has been difficult to elucidate. Recent studies with nucleosides and with a non-nucleoside reverse transcriptase inhibitor (NNRTI) address this issue. A multicenter virologic analysis of ACTG 116B/117 documented that the acquisition of AZT resistance conferred a worse prognosis even if ddl, to which the virus was susceptible, was administered instead of AZT. Preliminary observations using a quantitative PCR based assay that can discriminate allele specific populations of 215 WT or AZT resistant plasma HIV RNA suggest that AZT resistant virus may be less amenable to antiviral effects of nucleosides like ddl and ddC and of nevirapine.

A study of the NNRTI, nevirapine, has more clearly provided compelling evidence that loss of drug activity can be attributed to the acquisition of drug resistance. Moreover, the combination of nevi rapine with AZT resulted in a dramatic shift in the patterns of drug resistance mutations utilized by the virus. In addition when drug doses were increased to generate plasma levels that exceeded the susceptibility of the resistant virus, sustained antiviral activity was observed. This may have important implications for the development of many antiretroviral drugs, including protease inhibitors. Every protease inhibitor examined has selected for virus with diminished susceptibility in vitro. Numerous mutations have been identified in the protease gene, each antiviral compound selecting for certain mutations. The role of this resistance in therapeutic activity may be a critical issue in the development of protease inhibitors.

Presenting author: Douglas D. Richman, M.D

1994-11-18
3.2

Originally published in AIDS Volume 8, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

Copyright © 1994 - Lippincott Williams & Wilkins. All rights reserved. All abstracts from the 2nd International Congress Drug Therapy in HIV Infection, appearing on the AEGiS web site, are protected by United States copyright law and may not be reproduced, distributed, transmitted, displayed, or otherwise published without the prior written permission of Lippincott Williams & Wilkins. You may not alter or remove any trademark, copyright or other notice. However, provided that you maintain all copyright and other notices contained therein, you may download material (one machine readable copy and one print copy per page) for your personal, non-commercial use only.

http://www.aidsonline.com http://www.ovid.com