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

• Published in: Scientific reports Vol. 12; no. 1; pp. 18575 - 9
• Main Authors: Brombin, Chiara, Bagaglio, Sabrina, Cugnata, Federica, Castagna, Antonella, Uberti-Foppa, Caterina, Salpietro, Stefania, Di Serio, Clelia, Morsica, Giulia
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 639/705/531; 692/308/53; 692/499; 692/699/255; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Antiviral Agents - therapeutic use; Antiviral drugs; Biomarkers; CD4 antigen; CD8 antigen; eIF-2 kinase; eIF-2 Kinase - metabolism; Genotype & phenotype; Genotypes; Heterogeneity; HIV; HIV Infections - drug therapy; HIV Infections - genetics; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Interferon; Kinases; Latent class analysis; Longitudinal Studies; multidisciplinary; Protein biosynthesis; Protein kinase R; Protein synthesis; Proteins; Retrospective Studies; Science; Science (multidisciplinary); Viral Load
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-23289-4

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.