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Epidemiology. 2016 Mar;27(2):237-46. doi: 10.1097/EDE.0000000000000412.

Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children Ages 1-5 Years: A Causal Modeling Analysis.

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From the aCentre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa; bInstitute of Epidemiology and Public Health, University of Bordeaux, Bordeaux, France; cUniversity of Ghana Medical School, Accra, Ghana; dWits Reproductive Health and HIV Institute, Harriet Shezi Children's Clinic, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Soweto, South Africa; eCentre de Prise en Charge de Recherche et de Formation Enfants, Abidjan, Côte d'Ivoire; fEmpilweni Service and Research Unit, Rahima Moosa Mother and Child Hospital and University of the Witwatersrand, Johannesburg, South Africa; gYopougon University Hospital, Abidjan, Côte d'Ivoire; hAfrica Centre for Health and Population Studies, University of KwaZulu-Natal, Somkhele, South Africa; iAlbert Royer Hospital, Dakar, Senegal; jLighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi; kUniversity of North Carolina, Chapel Hill, NC; lFélix Houphouët Boigny University Hospital, Abidjan, Côte d'Ivoire; mMédecins Sans Frontiéres South Africa, CapeTown, South Africa; nKhayelitsha ART Programme, Khayelitsha, Cape Town, South Africa; oCharles de Gaulle University Hospital, Ouagadougou, Burkina Faso; pNewlands Clinic, Harare, Zimbabwe; qHospital du Tokoin, Lomé, Togo; rSinikithemba Clinic, McCord Hospital, Durban, South Africa; sMTCT-Plus Center, Abidjan, Côte d'Ivoire; tDesmond Tutu HIV Centre, Cape Town, South Africa; uInstitute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; vInstitute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; and wInserm, U897, Epidémiologie-Biostatistiques, Université Bordeaux, Bordeaux, France.



There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 1-5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups, and regions.


ART-naïve children of ages 12-59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation.


About one quarter of the 5,826 included children was from West Africa (24.6%).The median (first; third quartile) CD4% at the first visit was 16% (11%; 23%), the median weight-for-age z-scores and height-for-age z-scores were -1.5 (-2.7; -0.6) and -2.5 (-3.5; -1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count <750 cells/mm³ or CD4% <25% was 0.2% (95% CI = -0.2%; 0.3%), and the difference in the mean height-for-age z-scores of those who survived was -0.02 (95% CI = -0.04; 0.01). Younger children ages 1-2 and children in West Africa had worse outcomes.


Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, although we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below 750/25%.

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