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Drug resistance remains a major problem for the treatment of HIV. Resistancecan occur due to mutations that were present before treatment starts or due tomutations that occur during treatment. The relative importance of these twosources is unknown. We study three different situations in which HIV drugresistance may evolve: starting triple-drug therapy, treatment with a singledose of nevirapine and interruption of treatment. For each of these three casesgood data are available from literature, which allows us to estimate theprobability that resistance evolves from standing genetic variation. Dependingon the treatment we find probabilities of the evolution of drug resistance dueto standing genetic variation between 0 and 39%. For patients who starttriple-drug combination therapy, we find that drug resistance evolves fromstanding genetic variation in approximately 6% of the patients. We use apopulation-dynamic and population-genetic model to understand the observationsand to estimate important evolutionary parameters. We find that both, theeffective population size of the virus before treatment, and the fitness of theresistant mutant during treatment, are key-parameters that determine theprobability that resistance evolves from standing genetic variation.Importantly, clinical data indicate that both of these parameters can bemanipulated by the kind of treatment that is used.

Standing genetic variation and the evolution of drug resistance in HIV