resistance evolution

Feder AF, Thee S-Y, Holmes SP, Shafer RW, Petrov DA & Pennings PS 2016 More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1. eLife 5:e10670.

• we use 6717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013
• the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps

• whether populations evolve slowly or quickly is driven by the availability of adaptive mutations

• population genetic theory predicts that populations should evolve primarily by soft sweeps when resistance is likely and by hard sweeps when resistance is rare
• soft sweeps should mark cases of resistance that arise deterministically through many origins
• hard sweeps mark cases of rare, 'unlucky' resistance
• these predictions have not been tested in HIV or, in fact, in any natural population