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Int J Epidemiol. 2017 Apr 1;46(2):453-465. doi: 10.1093/ije/dyw097.

Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe.

Author information

1
Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
2
Inserm, U1027, Université Paul Sabatier Toulouse 3 Toulouse, France.
3
Children's Hospital/UMCU, Department of Infectious Diseases, Utrecht, The Netherlands.
4
Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa.
5
Empilweni Services and Research Unit, Department of Paediatrics & Child Health, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa.
6
University of Ghana Medical School, Accra, Ghana.
7
MRC Clinical Trials Unit, University College London, London, UK.
8
University of the Witwatersrand, Wits Reproductive Health and HIV Institute, Chris Hani Baragwanath Academic Hospital, Soweto, South Africa.
9
Félix Houphouët Boigny University Hospital, Abidjan, Côte d'Ivoire.
10
Pediatrics Department, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
11
Africa Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa.
12
School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.
13
Centre for the AIDS Programme of Research in South Africa - CAPRISA, University of KwaZulu-Natal, Congella, South Africa.
14
Yopougon University Hospital, Abidjan, Côte d'Ivoire.
15
Hospital Gregorio Marañón, Madrid, Spain.
16
Newlands Clinic, Harare, Zimbabwe.
17
MTCT-Plus Center, Abidjan, Côte d'Ivoire.
18
Centre de recherche en épidémiologie et santé des populations, 1018 Inserm, France.
19
Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi.
20
Centre de Prise en Charge de Recherche et de Formation Enfants, Abidjan, Côte d'Ivoire.
21
Médecins Sans Frontiéres South Africa, Cape Town, South Africa.
22
Charles de Gaulle University Hospital, Ouagadougou, Burkina Faso.
23
Sinikithemba Clinic, McCord Hospital, Durban, South Africa.
24
Albert Royer Hospital, Dakar, Senegal.
25
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
26
University of Bordeaux Bordeaux, ISPED, Centre INSERM U1219-Bordeaux Population Health, F-33000 Bordeaux, France.
27
INSERM, ISPED, Centre INSERM U1219-Bordeaux Population Health, F-33000 Bordeaux, France.
28
CHU de Bordeaux, Pôle de santé publique, Service d information médicale, F-33000 Bordeaux, France.

Abstract

Background:

There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents.

Methods:

A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula.

Results:

Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm 3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm 3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes.

Conclusions:

Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.

KEYWORDS:

Antiretroviral treatment; causal inference; g-formula; paediatrics

PMID:
27342220
PMCID:
PMC5837574
DOI:
10.1093/ije/dyw097
[Indexed for MEDLINE]
Free PMC Article

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