Mary-Ann Davies1, Margaret May, Carolyn Bolton-Moore, Cleophas Chimbetete, Brian Eley, Daniela Garone, Janet Giddy, Harry Moultrie, James Ndirangu, Sam Phiri, Helena Rabie, Karl-Günter Technau, Robin Wood, Andrew Boulle, Matthias Egger, Olivia Keiser. 1. From the *School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; †School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom; ‡Centre for Infectious Disease Research in Zambia, Lusaka, Zambia; §University of North Carolina, Chapel Hill, NC; ¶Newlands clinic, Harare, Zimbabwe; ‖Red Cross Children's Hospital and School of Child and Adolescent Health, University of Cape Town; **Médecins Sans Frontières (MSF) South Africa and Khayelitsha ART Programme, Cape Town; ††Sinikithemba Clinic, McCord Hospital, Durban; ‡‡Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg; §§Harriet Shezi Children's Clinic, Chris Hani Baragwanath Hospital, Soweto; ¶¶Africa Centre for Health and Population Studies, University of Kwazulu-Natal, Somkhele, South Africa; ‖‖Lighthouse Trust Clinic, Kamuzu Central Hospital, Lilongwe, Malawi and Liverpool School of Tropical Medicine, Liverpool, United Kingdom; ***Tygerberg Academic Hospital, University of Stellenbosch, Stellenbosch; †††Empilweni Services and Research Unit, Rahima Moosa Mother and Child Hospital, and University of the Witwatersrand, Johannesburg; ‡‡‡Gugulethu ART Programme and Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa; and §§§Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
Abstract
BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years of age who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004 to 2010. Children lost to follow up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct 2 prognostic models: 1 with CD4%, age, World Health Organization clinical stage, weight-for-age z-score (WAZ) and anemia and the other without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12,655 children, 877 (6.9%) died in the first year of ART. We excluded 1780 children who were lost to follow up/transferred from main analyses; 10,875 children were therefore included. With the CD4% model probability of death at 1 year ranged from 1.8% [95% confidence interval (CI): 1.5-2.3] in children 5-10 years with CD4% ≥10%, World Health Organization stage I/II, WAZ ≥ -2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% < 5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics = 0.753 and 0.745 for models with and without CD4%, respectively). CONCLUSIONS: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.
BACKGROUND: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. METHODS: We analyzed data from children ≤10 years of age who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004 to 2010. Children lost to follow up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct 2 prognostic models: 1 with CD4%, age, World Health Organization clinical stage, weight-for-age z-score (WAZ) and anemia and the other without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. RESULTS: Among 12,655 children, 877 (6.9%) died in the first year of ART. We excluded 1780 children who were lost to follow up/transferred from main analyses; 10,875 children were therefore included. With the CD4% model probability of death at 1 year ranged from 1.8% [95% confidence interval (CI): 1.5-2.3] in children 5-10 years with CD4% ≥10%, World Health Organization stage I/II, WAZ ≥ -2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% < 5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics = 0.753 and 0.745 for models with and without CD4%, respectively). CONCLUSIONS: These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.
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