Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges?

Author:

Smith R.J1

Affiliation:

1. Department of Mathematics and College of Veterinary Medicine, The University of Illinois at Urbana-Champaign2001 S. Lincoln Ave, Urbana IL 61802, USA

Abstract

The question of determining how many doses may be skipped before HIV treatment response is adversely affected by the emergence of drug-resistance is addressed. Impulsive differential equations are used to develop a prescription to minimize the emergence of drug-resistance for protease-sparing regimens. A threshold for the maximal number of missable doses is determined. If the number of missed doses is below this threshold, then resistance levels are negligible and dissipate quickly, assuming perfect adherence subsequently. If the number of missed doses exceeds this threshold, even for 24 h, resistance levels are extremely high and will not dissipate for weeks, even assuming perfect adherence subsequently. After this interruption, the minimum number of successive doses that should be taken is determined. Estimates are provided for all protease-sparing drugs approved by the US Food and Drug Administration. Estimates for the basic reproductive ratios for the wild-type and mutant strains of the virus are also calculated, for a long-term average fractional degree of adherence. There are regions within this fraction of adherence where the outcome is not predictable and may depend on a patient's entire history of drug-taking.

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

Reference24 articles.

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5. Bainov D.D& Simeonov P.S Impulsive differential equations: asymptotic properties of the solutions. 1995 Singapore:World Scientific.

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