  Drug resistance remains a major problem for the treatment of HIV. Resistance
can occur due to mutations that were present before treatment starts or due to
mutations that occur during treatment. The relative importance of these two
sources is unknown. We study three different situations in which HIV drug
resistance may evolve: starting triple-drug therapy, treatment with a single
dose of nevirapine and interruption of treatment. For each of these three cases
good data are available from literature, which allows us to estimate the
probability that resistance evolves from standing genetic variation. Depending
on the treatment we find probabilities of the evolution of drug resistance due
to standing genetic variation between 0 and 39%. For patients who start
triple-drug combination therapy, we find that drug resistance evolves from
standing genetic variation in approximately 6% of the patients. We use a
population-dynamic and population-genetic model to understand the observations
and to estimate important evolutionary parameters. We find that both, the
effective population size of the virus before treatment, and the fitness of the
resistant mutant during treatment, are key-parameters that determine the
probability that resistance evolves from standing genetic variation.
Importantly, clinical data indicate that both of these parameters can be
manipulated by the kind of treatment that is used.
