TY - JOUR TI - A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda AU - Blanquart, François AU - Grabowski, Mary Kate AU - Herbeck, Joshua AU - Nalugoda, Fred AU - Serwadda, David AU - Eller, Michael A AU - Robb, Merlin L AU - Gray, Ronald AU - Kigozi, Godfrey AU - Laeyendecker, Oliver AU - Lythgoe, Katrina A AU - Nakigozi, Gertrude AU - Quinn, Thomas C AU - Reynolds, Steven J AU - Wawer, Maria J AU - Fraser, Christophe A2 - Neher, Richard A VL - 5 PY - 2016 DA - 2016/11/05 SP - e20492 C1 - eLife 2016;5:e20492 DO - 10.7554/eLife.20492 UR - https://doi.org/10.7554/eLife.20492 AB - 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. KW - viral evolution KW - transmission-virulence trade-off KW - adaptation KW - quantitative genetics KW - selection JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -