A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 05, 2016
- Source ID
- 10.7554/elife.20492
Entities
People
- Christophe Fraser
- David Serwadda
- François Blanquart
- Fred Nalugoda
- Gertrude Nakigozi
- Godfrey Kigozi
- Joshua Herbeck
- Katrina A Lythgoe
- Maria J. Wawer
- Mary Kate Grabowski
- Merlin L Robb
- Michael A Eller
- Oliver Laeyendecker
- Ronald Gray
- Steven J. Reynolds
- Thomas C. Quinn
Organizations
- Big Data Institute
- European Commission
- European Research Council
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- Imperial College London
- John E. Fogarty Foundation
- Johns Hopkins University
- Makerere University
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Pfizer
- Rakai Health Sciences Program
- Rockefeller Foundation
- United States Department of Defense
- University of Oxford
- University of Washington
- Walter Reed Army Institute of Research
- World Bank