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

Author:

Ujeneza Eva Liliane12ORCID,Ndifon Wilfred2,Sawry Shobna3,Fatti Geoffrey45ORCID,Riou Julien6,Davies Mary-Ann7,Nieuwoudt Martin18,

Affiliation:

1. Department of Science and Technology and National Research Foundation, South African Centre for Epidemiological Modelling and Analysis (SACEMA), Stellenbosch University, Stellenbosch, South Africa

2. African Institute for Mathematical Sciences (AIMS), Next Einstein Initiative, Kigali, Rwanda

3. Harriet Shezi Children’s Clinic, Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

4. Kheth’Impilo AIDS Free Living, Cape Town, South Africa

5. Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

6. Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland

7. Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa

8. Institute for Biomedical Engineering (IBE), Stellenbosch University, Stellenbosch, South Africa

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 1616 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.

Funder

Schlumberger Stichting Fund, under the context of the Future Fellowship Program

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

National Institute Of Allergy And Infectious Diseases of the National Institutes of Health

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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