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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
When to Start Antiretroviral Therapy in Children Aged 2-5 Years: A Collaborative Causal Modelling Analysis of Cohort Studies from Southern Africa
PLoS Medicine, Volume 10, No. 11, Article e1001555, Year 2013
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Description
Background:There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4 percentage (CD4%) <25%.Methods and Findings:ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping.The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm3 (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm3 or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data.Conclusions:The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm3 or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values.Please see later in the article for the Editors' Summary. © 2013 Schomaker et al.
Authors & Co-Authors
Schomaker, Michael
South Africa, Cape Town
University of Cape Town
Egger, Matthias
Switzerland, Bern
University of Bern
Ndirangu, James
South Africa, Durban
University of Kwazulu-natal
Phiri, Sam John Peter
Malawi, Lilongwe
Kamuzu Central Hospital
United Kingdom, Liverpool
Liverpool School of Tropical Medicine
Malawi, Lilongwe
Lighthouse Trust
Moultrie, Harry
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
South Africa, Johannesburg
University of the Witwatersrand
Technau, Karl
South Africa, Johannesburg
Rahima Moosa Mother and Child Hospital
Cox, Vivian
Switzerland, Geneva
Medecins Sans Frontieres
South Africa, Cape Town
Khayelitsha Art Programme
Giddy, Janet
South Africa, Durban
Mccord Hospital
Chimbetete, Cleophas
Zimbabwe, Harare
Newlands Clinic
Wood, Robin Y.
South Africa, Cape Town
Desmond Tutu Health Foundation
South Africa, Cape Town
University of Cape Town
Gsponer, Thomas
Switzerland, Bern
University of Bern
Bolton Moore, Carolyn
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Zambia, Lusaka
Centre for Infectious Disease Research in Zambia
Rabie, Helena
South Africa, Tygerberg
Tygerberg Hospital
Eley, Brian S.
South Africa, Cape Town
University of Cape Town
Muhe, Lulu Mussa
Switzerland, Geneva
Organisation Mondiale de la Santé
Penazzato, Martina
Switzerland, Geneva
Organisation Mondiale de la Santé
United Kingdom, London
Medical Research Council
Essajee, Shaffiq M.
United States, Boston
Clinton Health Access Initiative, Inc.
Keiser, Olivia
Switzerland, Bern
University of Bern
Davies, M. A.
South Africa, Cape Town
University of Cape Town
Hoffmann, Christopher J.
South Africa, Johannesburg
The Aurum Institute
Chi, Benjamin H.
Zambia, Lusaka
Centre for Infectious Disease Research in Zambia
Naniche, Denise
Mozambique, Manhica
Centro de Investigação em Saúde de Manhiça Cism
Wood, Robin R.
South Africa, Cape Town
Desmond Tutu Health Foundation
Dickinson, Diana B.
Botswana, Gaborone
Independence Surgery
Stinson, Kathryn
Switzerland, Geneva
Medecins Sans Frontieres
Fatti, Geoffrey L.
South Africa
Kheth'impilo Programme
Wellington, Maureen
Zimbabwe, Harare
Newlands Clinic
Malisita, Kennedy
Malawi, Blantyre
Queen Elizabeth Central Hospital Malawi
Llenas-García, Jara
Mozambique, Pemba Region
Solidarmed Smart Programme
Fritz, Christiane
Zimbabwe, Masvingo
Solidarmed
Fox, Matthew P.
South Africa, Johannesburg
Themba Lethu Clinic
Maskew, Mhairi
South Africa, Johannesburg
Themba Lethu Clinic
Prozesky, Hans (Hw)
South Africa, Tygerberg
Tygerberg Hospital
Statistics
Citations: 33
Authors: 33
Affiliations: 28
Identifiers
Doi:
10.1371/journal.pmed.1001555
ISSN:
15491277
e-ISSN:
15491676
Research Areas
Infectious Diseases
Maternal And Child Health
Study Design
Cohort Study
Participants Gender
Male