A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda
Blanquart F., Grabowski MK., Herbeck J., Nalugoda F., Serwadda D., Eller MA., Robb ML., Gray R., Kigozi G., Laeyendecker O., Lythgoe KA., Nakigozi G., Quinn TC., Reynolds SJ., Wawer MJ., Fraser C.
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.