More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1

Elife. 2016 Feb 15;5:e10670. doi: 10.7554/eLife.10670.

Abstract

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 resistance 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 6717 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.

Keywords: HIV; drug resistance; evolutionary biology; evolutionary dynamics; genomics; soft sweeps; within-host evolutionary.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Biological
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use*
  • Drug Resistance, Viral*
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / drug effects*
  • Humans
  • Mutation Rate
  • Selection, Genetic*

Substances

  • Anti-HIV Agents