Comparison of different treatment regimens for the emergence of new resistance under therapy.
OBJECTIVE
To compare the effects of different therapy regimens on the probability of emergence of new resistant mutants during therapy.


METHODS
We developed a stochastic model of infection and treatment to calculate the probability of de novo resistance during therapy. We simulated diverse treatment regimens, with different efficacy in controlling HIV replication. We studied the use of genotypic testing to choose treatment protocols specifically tailored against the wild type.


RESULTS
The probability of emergence of a previously nonexisting drug-resistant mutant during therapy depends crucially on the drug regimen used. In particular, therapy protocols targeting the wild-type strain may lead to a higher probability of treatment failure due to resistance. Conversely, targeting the minority strains in the population, which readily mutate into the resistant variety, significantly lowers the probability of a new resistant emerging under therapy.


CONCLUSIONS
Use of genotypic testing may lead to wrong decisions in the choice of therapy if the population dynamics of production of new resistant mutants is not taken into account.
Roberts
D E
DE
Florida State University, Tallahassee, Florida, USA.
Ribeiro
R M
RM
D023241:Antiretroviral Therapy, Highly Active; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D009154:Mutation; D014779:Virus Replication / Q000187:drug effects