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

Eva Liliane Ujeneza,Martin Nieuwoudt,Geoffrey Fatti,Wilfred Ndifon,Shobna Sawry,Mary-Ann Davies,Julien Riou

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 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.

Highlights

The efficacy with which antiretroviral therapy (ART) suppresses human immunodeficiency virus (HIV) viral load and restores lymphocyte responses to pathogen-derived antigens, normally lost due to viral replication, is well established (Cooney, 2002; Autran et al, 1997)
Understanding its dynamics is crucial, to ensure that the best care is delivered to HIV-infected patients
Previous studies described CD4+ T-cell count dynamics in HIVtreated patients, using non-mechanistic (Sempa et al, 2017) and mechanistic models (Lewis et al, 2012; Means et al, 2016; Di Mascio et al, 2006), none provided a method that allows for direct comparison with age-matched healthy controls

Summary

Introduction

The efficacy with which antiretroviral therapy (ART) suppresses HIV viral load and restores lymphocyte responses to pathogen-derived antigens, normally lost due to viral replication, is well established (Cooney, 2002; Autran et al, 1997). Following ART initiation, for the majority of HIV-infected individuals, the CD4+ T-cell counts rapidly increase for approximately 4–6 months (Lawn et al, 2006), followed by a slower increase in the 2–4 years, after which cell numbers plateau (Pinzone et al, 2012). There is currently no cure for HIV, but antiretroviral therapies can keep the virus in check and allow individuals with HIV to live longer, healthier lives. They block the ability of the virus to multiply and they allow numbers of an important type of infection-fighting cell called CD4+ T cells to rebound

Methods

Results

Conclusion