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We use an epidemiological-evolutionary model parameterised with this data to derive evolutionary predictions based on analysis and detailed individual-based simulations. We robustly predict stabilising selection towards a low level of virulence, and rapid attenuation of the virus. Accordingly, set-point viral load, the most common measure of virulence, has declined in the last 20 years. Our model also predicts that subtype A is slowly outcompeting subtype D, with both subtypes becoming less virulent, as observed in the data. Reduction of set-point viral loads should have resulted in a 20% reduction in incidence, and a three years extension of untreated asymptomatic infection, increasing opportunities for timely treatment of infected individuals.<\/jats:p>","DOI":"10.7554\/elife.20492","type":"journal-article","created":{"date-parts":[[2016,11,5]],"date-time":"2016-11-05T09:00:10Z","timestamp":1478336410000},"source":"Crossref","is-referenced-by-count":55,"title":["A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda"],"prefix":"10.7554","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0591-2466","authenticated-orcid":true,"given":"Fran\u00e7ois","family":"Blanquart","sequence":"first","affiliation":[{"name":"MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, United Kingdom"},{"name":"Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom"},{"name":"School of Public Health, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary Kate","family":"Grabowski","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins University, Baltimore, United States"},{"name":"Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4577-7406","authenticated-orcid":true,"given":"Joshua","family":"Herbeck","sequence":"additional","affiliation":[{"name":"International Clinical Research Center, University of Washington, Seattle, United States"},{"name":"Department of Global Health, University of Washington, Seattle, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Nalugoda","sequence":"additional","affiliation":[{"name":"Rakai Health Sciences Program, Entebbe, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Serwadda","sequence":"additional","affiliation":[{"name":"Rakai Health Sciences Program, Entebbe, Uganda"},{"name":"School of Public Health, Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Eller","sequence":"additional","affiliation":[{"name":"U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States"},{"name":"Henry M. 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