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Relational concurrency, stages of infection, and the evolution of HIV set point viral load

HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that population mean...

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Autores principales: Goodreau, Steven M, Stansfield, Sarah E, Murphy, James T, Peebles, Kathryn C, Gottlieb, Geoffrey S, Abernethy, Neil F, Herbeck, Joshua T, Mittler, John E
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249390/
https://www.ncbi.nlm.nih.gov/pubmed/30483403
http://dx.doi.org/10.1093/ve/vey032
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author Goodreau, Steven M
Stansfield, Sarah E
Murphy, James T
Peebles, Kathryn C
Gottlieb, Geoffrey S
Abernethy, Neil F
Herbeck, Joshua T
Mittler, John E
author_facet Goodreau, Steven M
Stansfield, Sarah E
Murphy, James T
Peebles, Kathryn C
Gottlieb, Geoffrey S
Abernethy, Neil F
Herbeck, Joshua T
Mittler, John E
author_sort Goodreau, Steven M
collection PubMed
description HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that population mean SPVL (MSPVL) has evolved near an optimum that reflects a trade-off between transmissibility and host survival. Sexual network structures affect rates of potential exposure during different within-host phases of infection marked by different transmission probabilities, and thus affect the number and timing of transmission events. These structures include relational concurrency, which has been argued to explain key differences in HIV burden across populations. We hypothesize that concurrency will alter the fitness landscape for SPVL in ways that differ from other network features whose impacts accrue at other times during infection. To quantitatively test this hypothesis, we developed a dynamic, stochastic, data-driven network model of HIV transmission, and evolution to assess the impact of key sexual network phenomena on MSPVL evolution. Experiments were repeated in sensitivity runs that made different assumptions about transmissibility during acute infection, SPVL heritability, and the functional form of the relationship between VL and transmissibility. For our main transmission model, scenarios yielded MSPVLs ranging from 4.4 to 4.75 log(10) copies/ml, covering much of the observed empirical range. MSPVL evolved to be higher in populations with high concurrency and shorter relational durations, with values varying over a clinically significant range. In linear regression analyses on these and other predictors, main effects were significant (P < 0.05), as were interaction terms, indicating that effects are interdependent. We also noted a strong correlation between two key emergent properties measured at the end of the simulations—MSPVL and HIV prevalence—most clearly for phenomena that affect transmission networks early in infection. Controlling for prevalence, high concurrency yielded higher MSPVL than other network phenomena. Interestingly, we observed lower prevalence in runs in which SPVL heritability was zero, indicating the potential for viral evolution to exacerbate disease burden over time. Future efforts to understand empirical variation in MSPVL should consider local HIV burden and basic sexual behavioral and network structure.
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spelling pubmed-62493902018-11-27 Relational concurrency, stages of infection, and the evolution of HIV set point viral load Goodreau, Steven M Stansfield, Sarah E Murphy, James T Peebles, Kathryn C Gottlieb, Geoffrey S Abernethy, Neil F Herbeck, Joshua T Mittler, John E Virus Evol Research Article HIV viral load (VL) predicts both transmission potential and rate of disease progression. For reasons that are still not fully understood, the set point viral load (SPVL) established after acute infection varies across individuals and populations. Previous studies have suggested that population mean SPVL (MSPVL) has evolved near an optimum that reflects a trade-off between transmissibility and host survival. Sexual network structures affect rates of potential exposure during different within-host phases of infection marked by different transmission probabilities, and thus affect the number and timing of transmission events. These structures include relational concurrency, which has been argued to explain key differences in HIV burden across populations. We hypothesize that concurrency will alter the fitness landscape for SPVL in ways that differ from other network features whose impacts accrue at other times during infection. To quantitatively test this hypothesis, we developed a dynamic, stochastic, data-driven network model of HIV transmission, and evolution to assess the impact of key sexual network phenomena on MSPVL evolution. Experiments were repeated in sensitivity runs that made different assumptions about transmissibility during acute infection, SPVL heritability, and the functional form of the relationship between VL and transmissibility. For our main transmission model, scenarios yielded MSPVLs ranging from 4.4 to 4.75 log(10) copies/ml, covering much of the observed empirical range. MSPVL evolved to be higher in populations with high concurrency and shorter relational durations, with values varying over a clinically significant range. In linear regression analyses on these and other predictors, main effects were significant (P < 0.05), as were interaction terms, indicating that effects are interdependent. We also noted a strong correlation between two key emergent properties measured at the end of the simulations—MSPVL and HIV prevalence—most clearly for phenomena that affect transmission networks early in infection. Controlling for prevalence, high concurrency yielded higher MSPVL than other network phenomena. Interestingly, we observed lower prevalence in runs in which SPVL heritability was zero, indicating the potential for viral evolution to exacerbate disease burden over time. Future efforts to understand empirical variation in MSPVL should consider local HIV burden and basic sexual behavioral and network structure. Oxford University Press 2018-11-21 /pmc/articles/PMC6249390/ /pubmed/30483403 http://dx.doi.org/10.1093/ve/vey032 Text en © The Author(s) 2018. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Research Article
Goodreau, Steven M
Stansfield, Sarah E
Murphy, James T
Peebles, Kathryn C
Gottlieb, Geoffrey S
Abernethy, Neil F
Herbeck, Joshua T
Mittler, John E
Relational concurrency, stages of infection, and the evolution of HIV set point viral load
title Relational concurrency, stages of infection, and the evolution of HIV set point viral load
title_full Relational concurrency, stages of infection, and the evolution of HIV set point viral load
title_fullStr Relational concurrency, stages of infection, and the evolution of HIV set point viral load
title_full_unstemmed Relational concurrency, stages of infection, and the evolution of HIV set point viral load
title_short Relational concurrency, stages of infection, and the evolution of HIV set point viral load
title_sort relational concurrency, stages of infection, and the evolution of hiv set point viral load
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249390/
https://www.ncbi.nlm.nih.gov/pubmed/30483403
http://dx.doi.org/10.1093/ve/vey032
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