A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda.
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.
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.
François
0000-0003-0591-2466
F
Blanquart
Department of Epidemiology, Johns Hopkins University, Baltimore, United States.|Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Mary Kate
MK
Grabowski
International Clinical Research Center, University of Washington, Seattle, United States.|Department of Global Health, University of Washington, Seattle, United States.
Joshua
0000-0003-4577-7406
J
Herbeck
Rakai Health Sciences Program, Entebbe, Uganda.
Fred
F
Nalugoda
Rakai Health Sciences Program, Entebbe, Uganda.|School of Public Health, Makerere University, Kampala, Uganda.
David
D
Serwadda
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.
Michael A
MA
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
ML
Robb
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.
Ronald
R
Gray
Rakai Health Sciences Program, Entebbe, Uganda.
Godfrey
G
Kigozi
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.
Oliver
O
Laeyendecker
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.
Katrina A
KA
Lythgoe
Rakai Health Sciences Program, Entebbe, Uganda.
Gertrude
G
Nakigozi
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.
Thomas C
TC
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
SJ
Reynolds
Department of Epidemiology, Johns Hopkins University, Baltimore, United States.|Bloomberg School of Public Health, Johns Hopkins University, Baltimore, United States.
Maria J
MJ
Wawer
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.
Christophe
C
Fraser
D005075:Biological Evolution; D056084:Genetic Fitness / Q000235:genetics; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D008954:Models, Biological; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load / Q000235:genetics
adaptation; epidemiology; evolutionary biology; genomics; global health; quantitative genetics; selection; transmission-virulence trade-off; viral evolution; virus