A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda
- Imperial College London, United Kingdom
- Johns Hopkins University, United States
- University of Washington, United States
- Rakai Health Sciences Program, Uganda
- Walter Reed Army Institute of Research, United States
- National Institutes of Health, United States
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.
Data availability
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Data from: A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in UgandaAvailable at Dryad Digital Repository under a CC0 Public Domain Dedication.
Article and author information
Author details
François Blanquart
Funding
European Commission (Intra European Fellowship 657768)
- François Blanquart
World Bank Group
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
Henry M. Jackson Foundation (W81XWH-07-2-0067)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
U.S. Department of Defense (W81XWH-07-2-0067)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
National Institutes of Health (R01AI108490; P30AI027757)
- Joshua Herbeck
European Research Council (PBDR-339251)
- Christophe Fraser
National Institute of Allergy and Infectious Diseases (R01 Al 29314; R01 AI34826; UO1 AI11171-01-02)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
National Institute of Child Health and Human Development (5P30 HD 06268)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
John E. Fogarty Foundation for Persons with Intellectual and Developmental Disabilities (5D43TW00010)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
John Snow Inc. (5024-30)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
Pfizer (5024-30)
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
Rockefeller Foundation
- Mary Kate Grabowski
- Fred Nalugoda
- David Serwadda
- Michael A Eller
- Merlin L Robb
- Ronald Gray
- Godfrey Kigozi
- Oliver Laeyendecker
- Gertrude Nakigozi
- Thomas C Quinn
- Steven J Reynolds
- Maria J Wawer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Informed consent was obtained from all the participants in the Rakai Community Cohort Study.The Scientific and Ethics Committee of the Uganda Virus Research Institute (UVRI) of the Ministry of Health provides the Institutional Review Board approval and monitoring of all Rakai research.
Copyright
© 2016, Blanquart et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A transmission-virulence evolutionary trade-off explains attenuation of HIV-1 in Uganda
eLife 5:e20492.
https://doi.org/10.7554/eLife.20492
Further reading
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- Cancer Biology
- Epidemiology and Global Health
Cancer is considered a risk factor for COVID-19 mortality, yet several countries have reported that deaths with a primary code of cancer remained within historic levels during the COVID-19 pandemic. Here, we further elucidate the relationship between cancer mortality and COVID-19 on a population level in the US. We compared pandemic-related mortality patterns from underlying and multiple cause (MC) death data for six types of cancer, diabetes, and Alzheimer’s. Any pandemic-related changes in coding practices should be eliminated by study of MC data. Nationally in 2020, MC cancer mortality rose by only 3% over a pre-pandemic baseline, corresponding to ~13,600 excess deaths. Mortality elevation was measurably higher for less deadly cancers (breast, colorectal, and hematological, 2–7%) than cancers with a poor survival rate (lung and pancreatic, 0–1%). In comparison, there was substantial elevation in MC deaths from diabetes (37%) and Alzheimer’s (19%). To understand these differences, we simulated the expected excess mortality for each condition using COVID-19 attack rates, life expectancy, population size, and mean age of individuals living with each condition. We find that the observed mortality differences are primarily explained by differences in life expectancy, with the risk of death from deadly cancers outcompeting the risk of death from COVID-19.
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- Epidemiology and Global Health
Background:
The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer.
Methods:
Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed.
Results:
A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19–1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18–1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer.
Conclusions:
Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases.
Funding:
This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).
