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Title: Increased inflammation in sanctuary sites may explain viral blips in HIV infection

Abstract

Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days –1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R 0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection betweenmore » compartments.« less

Authors:
 [1];  [2];  [3]
  1. Pennsylvania State Univ., Malvern, PA (United States)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. of Delaware, Newark, DE (United States)
  3. Univ. of Delaware, Newark, DE (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1255268
Report Number(s):
LA-UR-16-20164
Journal ID: ISSN 1751-8849
Grant/Contract Number:
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
IET Systems Biology
Additional Journal Information:
Journal Name: IET Systems Biology; Journal ID: ISSN 1751-8849
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science

Citation Formats

Piovoso, Michael J., Cardozo, E. Fabian, and Zurakowski, Ryan. Increased inflammation in sanctuary sites may explain viral blips in HIV infection. United States: N. p., 2016. Web. doi:10.1049/iet-syb.2015.0066.
Piovoso, Michael J., Cardozo, E. Fabian, & Zurakowski, Ryan. Increased inflammation in sanctuary sites may explain viral blips in HIV infection. United States. doi:10.1049/iet-syb.2015.0066.
Piovoso, Michael J., Cardozo, E. Fabian, and Zurakowski, Ryan. 2016. "Increased inflammation in sanctuary sites may explain viral blips in HIV infection". United States. doi:10.1049/iet-syb.2015.0066. https://www.osti.gov/servlets/purl/1255268.
@article{osti_1255268,
title = {Increased inflammation in sanctuary sites may explain viral blips in HIV infection},
author = {Piovoso, Michael J. and Cardozo, E. Fabian and Zurakowski, Ryan},
abstractNote = {Here, combined antiretroviral therapy (cART) suppress HIV-1 viral replication, such that viral load in plasma remains below the limit of detection in standard assays. However, intermittent episodes of transient viremia (blips) occur in a set of HIV-patients. Given that follicular hyperplasia occurs during lymphoid inflammation as a normal response to infection, it is hypothesised that when the diameter of the lymph node follicle (LNF) increases and crosses a critical size, a viral blip occurs due to cryptic viremia. To study this hypothesis, a theoretical analysis of a mathematical model is performed to find the conditions for virus suppression in all compartments and different scenarios of LNF size changes are simulated. According to the analysis, blips with duration of around 30 days arise when the diameter rise rate is between 0.02 and 0.03 days–1. Moreover, the final diameter of the site is directly related to the steady states of the virus load after the occurrence of a blip. When the value of R0 is around 2.1, to have a steady-state below the limit of detection after the viral blip, the maximum final diameters should be greater than 0.7 mm so that there is a relative loss of connection between compartments.},
doi = {10.1049/iet-syb.2015.0066},
journal = {IET Systems Biology},
number = ,
volume = ,
place = {United States},
year = 2016,
month = 8
}

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