Comparison of predictors for terminal disease progression in simian immunodeficiency virus/simian-HIV-infected rhesus macaques.
Journal
AIDS (London, England)
ISSN: 1473-5571
Titre abrégé: AIDS
Pays: England
ID NLM: 8710219
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
pubmed:
13
3
2021
medline:
20
5
2021
entrez:
12
3
2021
Statut:
ppublish
Résumé
CD4+ T-cell decline and increasing virus levels are considered hallmarks of HIV/AIDS pathogenesis but we previously demonstrated in rhesus macaques that tissue macrophage destruction by simian immunodeficiency virus (SIV) infection associated with increased monocyte turnover also appear to impact pathogenesis. It remains unclear, however, which factors best predict onset of terminal disease progression and survival time. The objective of this study, therefore, was to directly compare these co-variates of infection for predicting survival times in retrospective studies of SIV/simian-HIV (SHIV)-infected adult rhesus macaques. Rhesus macaques were infected with various strains of SIV/SHIV and evaluated longitudinally for monocyte turnover, CD4+ T-cell loss, plasma viral load, and SIV/SHIV strain. Correlation analyses and machine learning algorithm modeling were applied to compare relative contributions of each of the co-variates to survival time. All animals with AIDS-related clinical signs requiring euthanasia exhibited increased monocyte turnover regardless of CD4+ T-cell level, viral strain, or plasma viral load. Regression analyses and machine learning algorithms indicated a stronger correlation and contribution between increased monocyte turnover and reduced survival time than between CD4+ T-cell decline, plasma viral load, or virus strain and reduced survival time. Decision tree modeling categorized monocyte turnover of 13.2% as the initial significant threshold that best predicted decreased survival time. These results demonstrate that monocytes/macrophages significantly affect HIV/SIV pathogenesis outcomes. Monocyte turnover analyses are not currently feasible in humans, so there is a need to identify surrogate biomarkers reflecting tissue macrophage damage that predict HIV infection disease progression.
Identifiants
pubmed: 33710021
doi: 10.1097/QAD.0000000000002874
pii: 00002030-202106010-00003
pmc: PMC8102323
mid: NIHMS1680200
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1021-1029Subventions
Organisme : NIAID NIH HHS
ID : R21 AI110163
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139278
Pays : United States
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NIH HHS
ID : P51 OD011104
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH108458
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH107333
Pays : United States
Organisme : NIAID NIH HHS
ID : R33 AI110163
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI097059
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG052349
Pays : United States
Informations de copyright
Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
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