Figure 5.

Reducing drug pressure will delay emergence and slow spread. The benefits of halving drug pressure can be enormous, but they must be considered within a finite time horizon. The x-axis shows baseline drug pressure. Baseline waiting times are plotted in blue. Baseline waiting times for halving drug pressure are plotted in red. The net benefit (the difference) is plotted in black. Top) Time to emerge (solid lines) combines the time to appear (dashed lines) with stochastic establishment. Middle) Clinical efficacy would be preserved for 20 years if drug pressure were low (red). Reducing drug pressure (blue) has a benefit in an intermediate range--when drug pressure is not low enough to make an intervention necessary but not high enough that resistance will rapidly fix, even if reduced. Bottom) For a reference parameter set, the combined effects of delaying emergence and slowing spread guarantee that MFTs will last 20 years. For high baseline drug pressure, the estimated waiting time to failure was as low as 5 years.