Recombination favors the evolution of drug resistance in HIV-1 during antiretroviral therapy.
We studied the relationship between recombination and the fixation time of multiple drug resistance mutations after HIV-1 drug therapy, under a set of different realistic scenarios. We have generalized a previous model by Bretscher et al. [Bretscher, Althaus, Muller, Bonhoeffer, 2004. Recombination in HIV and the evolution of drug resistance: for better or for worse? Bioessays 26(2), 180-188] in order to explore different implementations of phenotypic mixing and more realistic demographic and selective regimes. Using computer simulations we show that the effect of recombination on the evolution of drug resistance depends strongly on the intensity of selection, as well as on the viral population size. Under the high selection pressure expected during antiretroviral therapy, the strength of the Hill-Robertson effect increases and recombination favors the evolution of resistance under a wide range of population sizes, independently of the sign of the epistatic interaction. Our results suggest that recombination plays an important role in the evolution of drug resistance in HIV-1 under various realistic scenarios. These findings could be taken into account in order to develop optimal HIV-1 drug treatments.
Carvajal-Rodríguez
Antonio
A
Department of Microbiology and Molecular Biology, Brigham Young University, 84602 Provo, UT, USA. acraaj@uvigo.es
Crandall
Keith A
KA
Posada
David
D
D023241:Antiretroviral Therapy, Highly Active; D024921:Drug Resistance, Multiple, Viral; D019143:Evolution, Molecular; D015497:HIV-1 / Q000235:genetics*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics*; D013269:Stochastic Processes