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(BETA) News Briefs: Roche Investigators Say Invirase Does Not Cause Cross-Resistance to Other Protease Inhibitors




 

There is continuing controversy concerning the development of HIV resistance in vitro to the protease inhibitor drugs and the development of cross-resistance among these compounds. The most recent information on these subjects emerged at the Fourth HIV Drug Resistance Workshop in Sardinia, Italy (July 1995).

Simply stated, resistance refers to the ability of a microorganism (e.g., HIV) to overcome the inhibitory action of a drug used to suppress its replication. Cross-resistance refers to the development of resistance to one drug that also confers resistance to another drug (often a similar drug of the same class). New data presented at the Sardinia conference suggest that treatment with Invirase ( saquinavir) does not cause cross-resistance to other protease inhibitor drugs, including the Merck, Abbott and Vertex compounds, according to Italian researcher Stefano Vella, MD. In addition, the data suggest that HIV resistance to Invirase develops at a slower rate than seen with all other anti-HIV drugs, even after prolonged combination therapy with Invirase plus AZT.

If accurate, these data suggest that use of Invirase monotherapy does not threaten the efficacious use of other protease inhibitors now in development (e,.g., Crixivan, ritonavir, VX-478). Used in combination with other anti-HIV drugs, Invirase also may help to reduce the emergence of resistant strains of HIV.

Phase I/II studies of Invirase show that following 12 months of treatment, about 50% of study participants were still fully sensitive to the drug. Researchers say they discovered only a single critical mutation, L90M, or less commonly, G48V. These single mutations, say Roche investigators, lead to only a "modest" (3- to 10-fold) reduction in HIV sensitivity to Invirase. L90M and G48V are the only mutations consistently found after a year of treatment with Invirase monotherapy, Invirase plus AZT, or the triple combination of Invirase, AZT and ddC, according to Roche Swiss investigator Helmut Jacobsen, MD. "Additional results from the analysis of more than 1,500 protease sequences suggest that exposure to saquinavir (Invirase) does not select cross-resistance with other protease inhibitors," said Jacobsen. Laboratory studies presented in Sardinia by University of Wales researcher Sarah Wilson, MD, conclude that there is no cross-resistance between Invirase-resistant HIV and other, unrelated protease inhibitors.



 


Copyright © 1995 -BETA, Publisher. All rights reserved to the San Francisco AIDS Foundation. Reproduced by permission. Reproduction of this article (other than one copy for personal reference) must be cleared through BETA: PO Box 426182, San Francisco, CA 94142-6182. Tel: 415 487 8060 Fax: 415 487 8069 San Francisco AIDS Foundation, Mail SFAF..

Information in this article was accurate in September 1, 1995. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.