RT Journal Article SR Electronic T1 More efficacious drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 024109 DO 10.1101/024109 A1 Alison F. Feder A1 Soo-Yon Rhee A1 Robert W. Shafer A1 Dmitri A. Petrov A1 Pleuni S. Pennings YR 2015 UL http://biorxiv.org/content/early/2015/08/07/024109.abstract AB In the early days of HIV treatment, drug resistance occurred rapidly and predictably in all patients, but under modern treatments, resistance arises slowly, if at all. The probability of resistance should be controlled by the rate of generation of resistant mutations. If many adaptive mutations arise simultaneously, then adaptation proceeds by soft selective sweeps in which multiple adaptive mutations spread concomitantly, but if adaptive mutations occur rarely in the population, then a single adaptive mutation should spread alone in a hard selective sweep. Here we use 6,717 HIV-1 consensus sequences from patients treated with first-line therapies between 1989 and 2013 to confirm that the transition from fast to slow evolution of drug resistance was indeed accompanied with the expected transition from soft to hard selective sweeps. This suggests more generally that evolution proceeds via hard sweeps if resistance is unlikely and via soft sweeps if it is likely.