Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

Mary-Ann Davies,James Ndirangu,Maureen Wellington,Robin Wood,Karl Technau,Nicola Maxwell,Olivia Keiser,Brian Eley,Matthias Egger,Carolyn Bolton-Moore,Janet Giddy,Vivian Cox,Andrew Boulle,Venessa Timmerman,Harry Moultrie,Sam Phiri,Helena Rabie,Eduard J Beck

doi:10.1371/journal.pone.0081037

Abstract

BackgroundSince 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration.Methodology/Principal FindingsData from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<−3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines.Conclusions/SignificanceBetween 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.

Highlights

The estimated number of children receiving antiretroviral therapy (ART) in southern and eastern Africa has increased several-fold from,50,000 in 2005 to 337,200 by the end of December 2010, corresponding to a coverage of 26% of those eligible for ART [1]
Even after ART initiation, early mortality remains very high in children with advanced disease, whereas starting ART with less advanced disease is associated with a good prognosis in terms of mortality, immunological, growth and neurodevelopmental outcomes [7,8,9,10,11,12]
In addition to examining characteristics across the cohort as a whole, we aimed to focus on changes in infants starting therapy as the Children with HIV Early Antiretroviral Therapy (CHER) trial has shown that ART initiation in infants before disease progression substantially reduces mortality and morbidity [2,12,18,19]

Summary

Introduction

The estimated number of children receiving antiretroviral therapy (ART) in southern and eastern Africa has increased several-fold from ,50,000 in 2005 to 337,200 by the end of December 2010, corresponding to a coverage of 26% of those eligible for ART [1]. WHO 2010 guidelines recommended immediate ART for HIV infected children ,2 years of age irrespective of disease severity, and ART at much higher CD4 thresholds than before in older children [2]. This means that more children are starting therapy and increasingly those initiating treatment should have less advanced disease. Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration

Methods

Results

Conclusion