| Abstract | Induction-maintenance therapy is a treatment regime where patients are prescribed an intense course of treatment for a short period of time (the induction phase), followed by a simplified long-term regimen (maintenance). In this paper, we investigate, using mathematical modelling, the effect of imperfect adherence during the inductive phase. We address the following research questions: 1. Can we determine the maximal length of a drug holiday and the number of subsequent doses that must be taken to avoid resistance? 2. How many drug holidays can be taken during the induction phase? 3. Does the length of the induction period depend on the drug regimen? We show that, for a 180 day therapeutic program, a patient can take several drug holidays, but then has to follow each drug holiday with a strict, but fairly straightforward, drug-taking regimen. Since the results are dependent upon the drug regimen, we calculated the length and number of drug holidays for all fifteen protease-sparing triple-drug cocktails that have been approved by the US Food and Drug Administration. Our theoretical predictions are in line with recent results from pilot studies of short-cycle treatment interruption strategies and may be useful in guiding the design of future clinical trials. |
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