1. Microbiology and Infectious Disease
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A mechanistic model for long-term immunological outcomes in South African HIV-infected children and adults receiving ART

  1. Eva Liliane Ujeneza  Is a corresponding author
  2. Wilfred Ndifon
  3. Shobna Shawry
  4. Geoffrey Fatti
  5. Julien Riou
  6. Mary-Ann Davies
  7. Martin Nieuwoudt
  8. IeDEA-Southern Africa collaboration
  1. Stellenbosch University, South Africa
  2. African Institute for Mathematical Sciences Next Einstein Initiative, Rwanda
  3. University of the Witwatersrand, South Africa
  4. Kheth'Impilo AIDS Free Living, Division of Epidemiology and Biostatistics, South Africa
  5. University of Bern, Switzerland
  6. University of Cape Town, South Africa
Research Article
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Cite this article as: eLife 2021;10:e42390 doi: 10.7554/eLife.42390

Abstract

Long-term effects of the growing population of HIV-treated people in Southern Africa on individuals and the public health sector at large are not yet understood. This study proposes a novel 'ratio' model that relates CD4+ T-cell counts of HIV-infected individuals to the CD4+ count reference values from healthy populations. We use mixed-effects regression to fit the model to data from 1,616 children (median age 4.3 years at ART initiation) and 14,542 adults (median age 36 years at ART initiation). We found that the scaled carrying capacity, maximum CD4+ count relative to an HIV-negative individual of similar age, and baseline scaled CD4+ counts were closer to healthy values in children than in adults. Post-ART initiation, CD4+ growth rate was inversely correlated with baseline CD4+ T-cell counts, and consequently higher in adults than children. Our results highlight the impacts of age on dynamics of the immune system of healthy and HIV-infected individuals.

Data availability

Data used is from the International epidemiologic Databases to Evaluate AIDS Southern Africa collaboration. They maintain a database of routinely collected data from various clinics , mostly located in South Africa. We recommend that interested readers contact Dr. Morna Cornell, Project Manager IeDEA-SA in Cape Town (morna.cornell@uct.ac.za) to establish a data-sharing agreement. A research proposal highlighting how the data will be used is required.Source data for Figures / Figure supplements are provided and the Source code is available via GitHub.

Article and author information

Author details

  1. Eva Liliane Ujeneza

    DST/NRF South African Center for Epidemiological Modelling and Analysis (SACEMA), Mathematics, Stellenbosch University, Stellenbosch, South Africa
    For correspondence
    ujeneva@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5760-4847
  2. Wilfred Ndifon

    Research, African Institute for Mathematical Sciences Next Einstein Initiative, Kigali, Rwanda
    Competing interests
    The authors declare that no competing interests exist.
  3. Shobna Shawry

    Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  4. Geoffrey Fatti

    Research, Kheth'Impilo AIDS Free Living, Division of Epidemiology and Biostatistics, Cape Town, South Africa
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6467-662X
  5. Julien Riou

    Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Mary-Ann Davies

    Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine and Family Medecine, University of Cape Town, Cape Town, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  7. Martin Nieuwoudt

    DST/NRF South African Center for Epidemiological Modelling and Analysis, Institute for Biomedical Engineering (IBE), Stellenbosch University, Stellenbosch, South Africa
    Competing interests
    The authors declare that no competing interests exist.
  8. IeDEA-Southern Africa collaboration

Funding

Schlumberger Foundation

  • Eva Liliane Ujeneza

South African Department of Science and Technology and the National Research Foundation's Center of Excellence for Modelling and Analysis of Epidemiological Data

  • Eva Liliane Ujeneza

National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number (U01AI069924)

  • Mary-Ann Davies

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This study was approved as part of the IeDEA Southern African collaboration's protocol, by the Human Research Ethics Committee of the University of Cape Town, with a reference number N1810119 RECIP UCT 084/2006. Informed consent was obtained from all participants by the clinics collecting the data according to IeDEA protocols.

Reviewing Editor

  1. Miles P Davenport, University of New South Wales, Australia

Publication history

  1. Received: September 27, 2018
  2. Accepted: January 13, 2021
  3. Accepted Manuscript published: January 14, 2021 (version 1)
  4. Version of Record published: February 3, 2021 (version 2)

Copyright

© 2021, Ujeneza et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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