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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.<\/jats:p>","DOI":"10.7554\/elife.10670","type":"journal-article","created":{"date-parts":[[2016,2,12]],"date-time":"2016-02-12T20:16:14Z","timestamp":1455308174000},"source":"Crossref","is-referenced-by-count":92,"title":["More effective drugs lead to harder selective sweeps in the evolution of drug resistance in HIV-1"],"prefix":"10.7554","volume":"5","author":[{"given":"Alison F","family":"Feder","sequence":"first","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Yon","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Statistics, Stanford University, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Shafer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stanford University, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitri A","family":"Petrov","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pleuni S","family":"Pennings","sequence":"additional","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, United States"},{"name":"Department of Biology, San Francisco State University, San Francisco, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2016,2,14]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1111\/eva.12221","article-title":"Evolutionary rescue: linking theory for conservation and medicine","volume":"7","author":"Alexander","year":"2014","journal-title":"Evolutionary Applications"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"e4724","DOI":"10.1371\/journal.pone.0004724","article-title":"Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update","volume":"4","author":"Bennett","year":"2009","journal-title":"PloS One"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.1128\/JVI.02712-06","article-title":"The fitness cost of mutations associated with human immunodeficiency virus type 1 drug resistance is modulated by mutational interactions","volume":"81","author":"Cong","year":"2007","journal-title":"Journal of Virology"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1098\/rsbl.2011.1136","article-title":"Selective bird predation on the peppered moth: the last experiment of michael majerus","volume":"8","author":"Cook","year":"2012","journal-title":"Biology Letters"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1007\/s004380100531","article-title":"DDT resistance in correlates with over-expression and confers cross-resistance to the neonicotinoid imidacloprid","volume":"266","author":"Daborn","year":"2001","journal-title":"Molecular Genetics and Genomics"},{"key":"bib6","volume-title":"On the Origin of Species by Means of Natural Selection","author":"Darwin","year":"1859"},{"key":"bib7","article-title":"Panel on antiretroviral guidelines for adults & adolescents. guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents","author":"Department of Health & Human Services","unstructured":"Department of Health & Human Services. 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