Unveiling ecological/evolutionary insights in HIV viral load dynamics: Allowing random slopes to observe correlational changes to CpG-contents and other molecular and clinical predictors.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101484711 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-0067 (Electronic) Linking ISSN: 18780067 NLM ISO Abbreviation: Epidemics Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier
    • Subject Terms:
    • Abstract:
      In the context of infectious diseases, the dynamic interplay between ever-changing host populations and viral biology demands a more flexible modeling approach than common fixed correlations. Embracing random-effects regression models allows for a nuanced understanding of the intricate ecological and evolutionary dynamics underlying complex phenomena, offering valuable insights into disease progression and transmission patterns. In this article, we employed a random-effects regression to model an observed decreasing median plasma viral load (pVL) among individuals with HIV in Mexico City during 2019-2021. We identified how these functional slope changes (i.e. random slopes by year) improved predictions of the observed pVL median changes between 2019 and 2021, leading us to hypothesize underlying ecological and evolutionary factors. Our analysis involved a dataset of pVL values from 7325 ART-naïve individuals living with HIV, accompanied by their associated clinical and viral molecular predictors. A conventional fixed-effects linear model revealed significant correlations between pVL and predictors that evolved over time. However, this fixed-effects model could not fully explain the reduction in median pVL; thus, prompting us to adopt random-effects models. After applying a random effects regression model-with random slopes and intercepts by year-, we observed potential "functional changes" within the local HIV viral population, highlighting the importance of ecological and evolutionary considerations in HIV dynamics: A notably stronger negative correlation emerged between HIV pVL and the CpG content in the pol gene, suggesting a changing immune landscape influenced by CpG-induced innate immune responses that could impact viral load dynamics. Our study underscores the significance of random effects models in capturing dynamic correlations and the crucial role of molecular characteristics like CpG content. By enriching our understanding of changing host-virus interactions and HIV progression, our findings contribute to the broader relevance of such models in infectious disease research. They shed light on the changing interplay between host and pathogen, driving us closer to more effective strategies for managing infectious diseases. SIGNIFICANCE OF THE STUDY: This study highlights a decreasing trend in median plasma viral loads among ART-naïve individuals living with HIV in Mexico City between 2019 and 2021. It uncovers various predictors significantly correlated with pVL, shedding light on the complex interplay between host-virus interactions and disease progression. By employing a random-slopes model, the researchers move beyond traditional fixed-effects models to better capture dynamic correlations and evolutionary changes in HIV dynamics. The discovery of a stronger negative correlation between pVL and CpG content in HIV-pol sequences suggests potential changes in the immune landscape and innate immune responses, opening avenues for further research into adaptive changes and responses to environmental shifts in the context of HIV infection. The study's emphasis on molecular characteristics as predictors of pVL adds valuable insights to epidemiological and evolutionary studies of viruses, providing new avenues for understanding and managing HIV infection at the population level.
      Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
    • References:
      Viruses. 2020 May 25;12(5):. (PMID: 32466170)
      Annu Rev Immunol. 2002;20:709-60. (PMID: 11861616)
      Nature. 2000 Dec 7;408(6813):740-5. (PMID: 11130078)
      Immunity. 2012 Sep 21;37(3):426-40. (PMID: 22999948)
      N Engl J Med. 2001 Feb 15;344(7):472-80. (PMID: 11172188)
      Sci China Life Sci. 2013 Nov;56(11):1014-9. (PMID: 24114445)
      Sex Transm Infect. 2012 Dec;88 Suppl 2:i76-85. (PMID: 23172348)
      Curr Opin HIV AIDS. 2019 May;14(3):194-204. (PMID: 30925534)
      Philos Trans A Math Phys Eng Sci. 2016 Apr 13;374(2065):20150202. (PMID: 26953178)
      PLoS Comput Biol. 2008 Nov;4(11):e1000225. (PMID: 19023406)
      J Med Internet Res. 2023 Mar 29;25:e43277. (PMID: 36989038)
      Front Immunol. 2022 Aug 02;13:943481. (PMID: 35983032)
      N Engl J Med. 2000 Mar 30;342(13):921-9. (PMID: 10738050)
      J Anim Ecol. 2020 Jan;89(1):80-92. (PMID: 31454066)
      Infect Genet Evol. 2013 Oct;19:337-48. (PMID: 23660484)
      Clin Microbiol Rev. 2019 May 15;32(3):. (PMID: 31092508)
      Front Immunol. 2016 Jan 18;6:665. (PMID: 26834742)
      J Virol. 2018 Jan 2;92(2):. (PMID: 29093100)
      JAMA. 2019 Feb 5;321(5):451-452. (PMID: 30629090)
      Infect Genet Evol. 2017 Oct;54:98-107. (PMID: 28645708)
      AIDS Res Hum Retroviruses. 1995 Nov;11(11):1413-6. (PMID: 8573400)
      Annu Rev Med. 2003;54:535-51. (PMID: 12525683)
      Int J Epidemiol. 1998 Oct;27(5):897-903. (PMID: 9839750)
      Nat Rev Immunol. 2013 Dec;13(12):875-87. (PMID: 24157572)
      Sci Rep. 2017 Aug 15;7(1):8162. (PMID: 28811638)
      J Infect Dis. 1999 Sep;180(3):666-72. (PMID: 10438353)
      Nature. 2008 Nov 6;456(7218):98-101. (PMID: 18758442)
      AIDS. 2004 Jan 1;18 Suppl 1:S87-98. (PMID: 15075503)
      AIDS Res Hum Retroviruses. 2015 Apr;31(4):401-11. (PMID: 25347163)
      J Virol. 2014 Aug;88(15):8242-55. (PMID: 24829343)
      Mol Biol Evol. 2010 Jun;27(6):1257-68. (PMID: 20097660)
      AIDS Res Ther. 2020 Nov 12;17(1):66. (PMID: 33183355)
      J Clin Microbiol. 2012 Jun;50(6):1936-42. (PMID: 22403431)
      Science. 2013 Apr 5;340(6128):87-91. (PMID: 23559252)
      Clin Infect Dis. 2015 Nov 1;61(9):1462-8. (PMID: 26129754)
      Lancet. 1998 Nov 7;352(9139):1510-4. (PMID: 9820299)
      Ecology. 2019 Apr;100(4):e02644. (PMID: 30714129)
      Ecol Appl. 2019 Apr;29(3):e01852. (PMID: 30653797)
      Clin Infect Dis. 2006 Jun 1;42(11):1608-18. (PMID: 16652319)
      J Virol. 2020 Feb 28;94(6):. (PMID: 31748389)
      Stat Med. 2008 Jul 10;27(15):2865-73. (PMID: 17960576)
      PLoS Pathog. 2023 May 5;19(5):e1011357. (PMID: 37146066)
      Nat Commun. 2019 Dec 19;10(1):5788. (PMID: 31857582)
    • Grant Information:
      P30 AI036214 United States AI NIAID NIH HHS; R01 AI135992 United States AI NIAID NIH HHS
    • Contributed Indexing:
      Keywords: Biological markers; CpG islands; HIV viral load; Prognostic factors; Regression analysis
    • Publication Date:
      Date Created: 20240518 Date Completed: 20240615 Latest Revision: 20240629
    • Publication Date:
      20240629
    • Accession Number:
      PMC11213286
    • Accession Number:
      10.1016/j.epidem.2024.100770
    • Accession Number:
      38761432