…hopefully what we are seeing here in terms of resistance are the adverse consequences of using a weak inhibitor up front - the HIV space might provide an instructive analogy.
The HIV analogy might not be entirely appropriate. The resistance problem that permeated the HIV landscape in the early days of HAART regimens was not so much that the early drugs were weak agents, but rather that they made multi-drug compliance extremely difficult. For instance, the constituents of Truvada are not monumentally better antiretroviral agents than the older nucleoside drugs they superseded, but Truvada resulted in a very large improvement in patient compliance.
“The efficient-market hypothesis may be the foremost piece of B.S. ever promulgated in any area of human knowledge!”