@article{13bffab26166431e8d02dce913a9c50a,
title = "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.",
author = "Fran{\c c}ois Blanquart and Grabowski, {Mary Kate} and Joshua Herbeck and Fred Nalugoda and David Serwadda and Eller, {Michael A.} and Robb, {Merlin L.} and Ronald Gray and Godfrey Kigozi and Oliver Laeyendecker and Lythgoe, {Katrina A.} and Gertrude Nakigozi and Quinn, {Thomas C.} and Reynolds, {Steven J.} and Wawer, {Maria J.} and Christophe Fraser",
note = "Funding Information: We thank Troy Day, Florence D{\'e}barre, Sylvain Gandon, Prabhat Jha, Richard Neher and an anonymous reviewer for useful comments. FB is supported by a Marie Sk{\l}odowska-Curie Individual Fellowship (grant number 657768). JTH is supported by grants from the U.S. National Institutes of Health (R01AI108490 to JTH, and P30AI027757 to the University of Washington Center for AIDS Research). CF is supported by the European Research Council (Advanced Grant PBDR-339251). This work is supported by the National Institutes of Health (NIH), National Institute of Allergy and Infectious Diseases (NIAID) (grant R01 AI 29314, R01 AI34826); the NIH, NIAID, Division of AIDS, and in part the NIH, NIAID, Division of Intramural Research (grant U01 AI11171-01-02); the National Institute of Child Health and Development, Johns Hopkins Population Center (grant 5P30 HD 06268); the Fogarty Foundation (grant 5D43TW00010); John Snow Inc, Pfizer Inc (grant 5024-30); the Rockefeller Foundation; the World Bank STI Project, Uganda; a cooperative agreement (W81XWH-07-2-0067) between the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of Defense, nor the US Government. Publisher Copyright: {\textcopyright} Blanquart et al.",
year = "2016",
month = nov,
day = "5",
doi = "10.7554/eLife.20492",
language = "English (US)",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
number = "NOVEMBER2016",
}