A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda

François Blanquart, Mary Grabowski, Joshua Herbeck, Fred Nalugoda, David Serwadda, Michael A. Eller, Merlin L. Robb, Ronald H Gray, Godfrey Kigozi, Oliver B. Laeyendecker, Katrina A. Lythgoe, Gertrude Nakigozi, Thomas C Quinn, Steven James Reynolds, Maria J Wawer, Christophe Fraser

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere20492
JournaleLife
Volume5
Issue numberNOVEMBER2016
DOIs
StatePublished - Nov 5 2016

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Uganda
Virulence
HIV-1
Pathogens
Viral Load
Viruses
Asymptomatic Infections
Incidence

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Blanquart, F., Grabowski, M., Herbeck, J., Nalugoda, F., Serwadda, D., Eller, M. A., ... Fraser, C. (2016). A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda. eLife, 5(NOVEMBER2016), [e20492]. https://doi.org/10.7554/eLife.20492

A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda. / Blanquart, François; Grabowski, Mary; Herbeck, Joshua; Nalugoda, Fred; Serwadda, David; Eller, Michael A.; Robb, Merlin L.; Gray, Ronald H; Kigozi, Godfrey; Laeyendecker, Oliver B.; Lythgoe, Katrina A.; Nakigozi, Gertrude; Quinn, Thomas C; Reynolds, Steven James; Wawer, Maria J; Fraser, Christophe.

In: eLife, Vol. 5, No. NOVEMBER2016, e20492, 05.11.2016.

Research output: Contribution to journalArticle

Blanquart, F, Grabowski, M, Herbeck, J, Nalugoda, F, Serwadda, D, Eller, MA, Robb, ML, Gray, RH, Kigozi, G, Laeyendecker, OB, Lythgoe, KA, Nakigozi, G, Quinn, TC, Reynolds, SJ, Wawer, MJ & Fraser, C 2016, 'A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda', eLife, vol. 5, no. NOVEMBER2016, e20492. https://doi.org/10.7554/eLife.20492
Blanquart F, Grabowski M, Herbeck J, Nalugoda F, Serwadda D, Eller MA et al. A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda. eLife. 2016 Nov 5;5(NOVEMBER2016). e20492. https://doi.org/10.7554/eLife.20492
Blanquart, François ; Grabowski, Mary ; Herbeck, Joshua ; Nalugoda, Fred ; Serwadda, David ; Eller, Michael A. ; Robb, Merlin L. ; Gray, Ronald H ; Kigozi, Godfrey ; Laeyendecker, Oliver B. ; Lythgoe, Katrina A. ; Nakigozi, Gertrude ; Quinn, Thomas C ; Reynolds, Steven James ; Wawer, Maria J ; Fraser, Christophe. / A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in uganda. In: eLife. 2016 ; Vol. 5, No. NOVEMBER2016.
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