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

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 ari...

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Bibliographic Details
Published in:eLife 2016-02, Vol.5
Main Authors: Feder, Alison F, Rhee, Soo-Yon, Holmes, Susan P, Shafer, Robert W, Petrov, Dmitri A, Pennings, Pleuni S
Format: Article
Language:English
Subjects:
Adaptation
Adaptation, Biological
Anti-HIV Agents - pharmacology
Anti-HIV Agents - therapeutic use
Biology
Drug Resistance
Drug resistance in microorganisms
Drug Resistance, Viral
Evolution
Evolutionary Dynamics
Generalized linear models
Genetic diversity
Genomics and Evolutionary Biology
Genotype
Health aspects
HIV
HIV (Viruses)
HIV Infections - drug therapy
HIV Infections - virology
HIV-1 - drug effects
Human immunodeficiency virus
Humans
Mutation
Mutation Rate
Observations
Patients
Population
Selection, Genetic
Soft Sweeps
Within-host evolutionary
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Summary: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.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.10670