Variations in the characteristics and outcomes of children living with HIV following universal ART in sub-Saharan Africa (2006–17): a retrospective cohort study

Background: The proportion of children living with HIV and receiving antiretroviral therapy (ART) in sub-Saharan Africa has increased greatly since 2006, yet the changes in their demographic characteristics and treatment outcomes have not been well described. We examine the trends in characteristics and outcomes of children living with HIV who were younger than 5 years at ART initiation, and compare outcomes over time and across country income groups. Methods: We conducted a retrospective cohort analysis of data from children living with HIV who were younger than 5 years at ART initiation from 45 paediatric sites in 16 low-income, lower-middle-income, and upper-middle-income countries in sub-Saharan Africa (Benin, Burundi, Côte d'Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe). Outcomes were trends in patient characteristics at ART initiation (age, weight, height, and CD4%), and comparisons of mortality and loss to follow-up during ART over time and in various economic settings. We identified risk factors for mortality using Cox proportional hazards models. Each participating region had relevant institutional ethics review board approvals to contribute data to the analysis. Findings: We included 32 221 children living with HIV and initiating ART younger than 5 years between Jan 1, 2006, and Dec 31, 2017. Median age at ART initiation was 20·4 months (IQR 9·4–36·0) in 2006–10, 19·2 months (8·3–33·6) in 2011–13, and 19·2 months (8·8–33·7) in 2014–17. Median age at ART initiation was 13·2 months (IQR 4·7–26·8) in upper-middle-income countries, 22·6 months (13·2–37·5) in lower-middle-income countries and 24·2 months (13·5–39·1) in low-income countries. The proportion of children initiating ART younger than 3 months increased from 770 (5·1%) of 14 943 children in 2006–10 to 728 (10·0%) of 7290 children in 2014–17. The proportion of children initiating ART with severe immunosuppression decreased from 5469 (74·7%) of 7314 children for whom CD4% data were available in 2006–10 to 2353 (55·2%) of 4269 children in 2014–17. Mortality at 24 months on ART decreased from 970 (6·5%) of 14 943 children in 2006–10 to 214 (2·9%) of 7290 children in 2014–17. Loss to follow-up was 20·5% (95% CI 20·1–21·0) overall, and was similar across time periods. In multivariable analysis, lower mortality was observed for more recent ART initiation cohorts (adjusted hazard ratio 0·70, 95% CI 0·63–0·79 for 2011–13; 0·53, 0·45–0·72 for 2014–17 vs 2006–10) and for those residing in an upper-middle-income country (0·42, 0·35–0·49 vs low-income countries). Interpretation: Mortality declined significantly after universal ART recommendations for children younger than 2 years in 2010 and children younger than 5 years in 2013. However, substantial variations persisted across country income groups, and one in five children continue to be lost to follow-up. Targeted interventions are required to improve outcomes of children living with HIV, especially in the poorest countries. Funding: National Institute of Allergy and Infectious Disease.