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

View ORCID ProfileAlison F. Feder, View ORCID ProfileSoo-Yon Rhee, View ORCID ProfileRobert W. Shafer, View ORCID ProfileDmitri A. Petrov, View ORCID ProfilePleuni S. Pennings
doi: https://doi.org/10.1101/024109
Alison F. Feder
1Department of Biology, Stanford University, Stanford, CA
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  • For correspondence: afeder@stanford.edu
Soo-Yon Rhee
2Department of Medicine, Stanford University, Stanford, CA
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Robert W. Shafer
2Department of Medicine, Stanford University, Stanford, CA
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Dmitri A. Petrov
1Department of Biology, Stanford University, Stanford, CA
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Pleuni S. Pennings
1Department of Biology, Stanford University, Stanford, CA
3Department of Biology, San Francisco State University, San Francisco, CA
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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 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.

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Posted August 07, 2015.
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More efficacious drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1
Alison F. Feder, Soo-Yon Rhee, Robert W. Shafer, Dmitri A. Petrov, Pleuni S. Pennings
bioRxiv 024109; doi: https://doi.org/10.1101/024109
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More efficacious drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1
Alison F. Feder, Soo-Yon Rhee, Robert W. Shafer, Dmitri A. Petrov, Pleuni S. Pennings
bioRxiv 024109; doi: https://doi.org/10.1101/024109

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