Modelling the impact of protein-kinase R allelic variant on HIV biomarkers trajectories by means of latent class mixed models.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
03 11 2022
Historique:
received: 06 06 2022
accepted: 28 10 2022
entrez: 4 11 2022
pubmed: 5 11 2022
medline: 8 11 2022
Statut: epublish

Résumé

This paper is based on a retrospective longitudinal study on people living with HIV under antiretroviral treatment (ART) where allelic variants (either heterozygous CT genotype or homozygous CC genotype) have been evaluated at position -168 of the promoter region of the protein kinase R (-168/PKR). In general, antiviral effects of interferon are partially mediated by a RNA-dependent protein kinase (PKR) that, once activated, inhibits protein synthesis. Indeed, activation of PKR response can inhibit HIV replication. To explore the role of allelic variants in shaping dynamics of commonly monitored HIV biomarkers, CD4 cells, CD8 cells and HIV-load were modelled within a latent class mixed model (LCMM) to account for participants' heterogeneity over time. The estimated models identified two sub-groups from CD4 and HIV-load dynamics, revealing better outcomes for subgroups of participants with the heterozygous CT genotype. Heterozygous CT subjects in one of the two identified subgroups exhibited higher increase of CD4 cells and more marked decrease of HIV-load, over time, with respect to the homozygous CC subjects assigned to the same group.

Identifiants

pubmed: 36329104
doi: 10.1038/s41598-022-23289-4
pii: 10.1038/s41598-022-23289-4
pmc: PMC9633692
doi:

Substances chimiques

Biomarkers 0
Antiviral Agents 0
eIF-2 Kinase EC 2.7.11.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

18575

Informations de copyright

© 2022. The Author(s).

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Auteurs

Chiara Brombin (C)

University Centre for Statistics in the Biomedical Sciences (CUSSB), Milan, Italy. brombin.chiara@hsr.it.
Vita-Salute San Raffaele University, Milan, Italy. brombin.chiara@hsr.it.

Sabrina Bagaglio (S)

Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Federica Cugnata (F)

University Centre for Statistics in the Biomedical Sciences (CUSSB), Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.

Antonella Castagna (A)

Vita-Salute San Raffaele University, Milan, Italy.
Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Caterina Uberti-Foppa (C)

Vita-Salute San Raffaele University, Milan, Italy.
Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Stefania Salpietro (S)

Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Clelia Di Serio (C)

University Centre for Statistics in the Biomedical Sciences (CUSSB), Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Biomedical Faculty, Università della Svizzera Italiana, 6900, Lugano, Switzerland.

Giulia Morsica (G)

Department of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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