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Mutation Takes No Vacation: Can Structured Treatment Interruptions Increase the Risk of Drug-Resistant HIV-1?

Dorman Karin S.; Kaplan, Andrew H.; Lange, Kenneth; Sinsheimer, Janet S.
JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15th, 2000
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We use a mathematical model to study the dynamics of HIV-1 replication during structured treatment interruptions (STIs) in infected patients. The model predicts rapid viral rebound, restoration of a latently infected cell pool, and critically, partially resistant mutant rebound that may be missed because of high levels of wild type virus. Because partially resistant viruses are capable of mutating to full resistance, a substantial increase in their numbers represents a threat to therapeutic response durability. Compared with continued treatment, STIs may increase the chance of mutation to full resistance by several thousandfold.

Address correspondence and reprint requests to Janet Sinsheimer, Department of Biomathematics, University of California Los Angeles School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1766 U.S.A.;

© 2000 Lippincott Williams & Wilkins, Inc.