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

• Published in: eLife Vol. 5
• Main Authors: Blanquart, François, Grabowski, Mary Kate, Herbeck, Joshua, Nalugoda, Fred, Serwadda, David, Eller, Michael A, Robb, Merlin L, Gray, Ronald, Kigozi, Godfrey, Laeyendecker, Oliver, Lythgoe, Katrina A, Nakigozi, Gertrude, Quinn, Thomas C, Reynolds, Steven J, Wawer, Maria J, Fraser, Christophe
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 05.11.2016; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Acquired immune deficiency syndrome; adaptation; AIDS; Asymptomatic infection; Biological Evolution; Epidemiology; Epidemiology and Global Health; Evolution; Generalized linear models; Genetic Fitness - genetics; Genomics and Evolutionary Biology; Health aspects; Health sciences; HIV; HIV Infections - epidemiology; HIV Infections - genetics; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - pathogenicity; Host-Pathogen Interactions - genetics; Human immunodeficiency virus; Humans; Hypotheses; Infections; Infectious diseases; Models, Biological; Observations; Pathogens; Public health; quantitative genetics; Reproductive fitness; selection; transmission-virulence trade-off; Trends; Uganda - epidemiology; viral evolution; Viral Load - genetics; Virulence; Virulence (Microbiology); Uganda; global health; epidemiology; quantitative genetics; evolutionary biology; selection; viral evolution; adaptation; genomics; virus; transmission-virulence trade-off
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.20492

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.