MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, United Kingdom; Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom; School of Public Health, Imperial College London, London, United Kingdom
Mary Kate Grabowski
Department of Epidemiology, Johns Hopkins University, Baltimore, United States; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States
International Clinical Research Center, University of Washington, Seattle, United States; Department of Global Health, University of Washington, Seattle, United States
Fred Nalugoda
Rakai Health Sciences Program, Entebbe, Uganda
David Serwadda
Rakai Health Sciences Program, Entebbe, Uganda; School of Public Health, Makerere University, Kampala, Uganda
Michael A Eller
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Merlin L Robb
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, United States; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, United States
Ronald Gray
Department of Epidemiology, Johns Hopkins University, Baltimore, United States; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States; Rakai Health Sciences Program, Entebbe, Uganda
Godfrey Kigozi
Rakai Health Sciences Program, Entebbe, Uganda
Oliver Laeyendecker
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
Katrina A Lythgoe
MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, United Kingdom; Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom; School of Public Health, Imperial College London, London, United Kingdom; Department of Zoology, University of Oxford, Oxford, United Kingdom
Gertrude Nakigozi
Rakai Health Sciences Program, Entebbe, Uganda
Thomas C Quinn
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
Steven J Reynolds
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, United States
Maria J Wawer
Department of Epidemiology, Johns Hopkins University, Baltimore, United States; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States
Christophe Fraser
MRC Centre for Outbreak Analysis and Modelling, Imperial College London, London, United Kingdom; Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom; School of Public Health, Imperial College London, London, United Kingdom; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
Evolutionary theory hypothesizes that intermediate virulence maximizes pathogen fitness as a result of a trade-off between virulence and transmission, but empirical evidence remains scarce. We bridge this gap using data from a large and long-standing HIV-1 prospective cohort, in Uganda. 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.
