How and why does resistance emerge?–
Competition within the prevailing
competitive edge depends on the prevailing environment of the virus; use of one or more suppressive antiretrovirals changes
the environment to favour
other populations over the wild-type.
with even a very small degree of resistance to one or more of the drugs used will quickly seize the bulk of the
residual replication under therapy;
these so-called ‘escape mutants’ may not cause regimen failure directly, but will provide the ‘backbone’ for further,
stepwise accumulation of mutations
increasing the degree of resistance to give an eventual outgrowth.
multiple drugs in a regimen significantly delays the development of resistance in two ways:
•By markedly reducing the likelihood of there being a pre-existing escape mutant in the quasispecies, particularly
if more than a single mechanistic
class is employed.
•By reducing residual replication by a much greater amount
than that derived from only one or
principle, a sufficient number of drugs in a regimen might be expected to suppress replication to such a degree that, even were an
escape mutant to eventually emerge, it would
be functionally disabled and non-reproductive.
to date, no combination of drugs has proved to be ‘resistance-proof’ in this way.