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 publication

DOI

10.7554/elife.20492

Type

Journal article

Journal

eLife

Publication Date

05/11/2016

Volume

5

Addresses

School of Public Health, Imperial College London, London, United Kingdom.

Keywords

Humans, HIV-1, HIV Infections, Viral Load, Models, Biological, Uganda, Host-Pathogen Interactions, Genetic Fitness, Biological Evolution