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