The authors of this retrospective cohort analysis, noting a lack of data on how the expansion of ART affected pediatric patient populations, wrote: “Several observational studies have described the results of children with HIV from some cohorts and in the pre-ART era. Moreover, we have not found any studies comparing the results of young children with HIV in different economic situations. “
Their primary outcomes were mortality and loss to follow-up during ART as influenced by different economic conditions, with patients less than 5 years old (N = 32,221) from 16 low, low, and upper middle income countries in SSA. (Benin, Burundi, Ivory Coast, Democratic Republic of Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia and Zimbabwe) which ART founded between January 1, 2006, and December 31, 2017.
For the three periods evaluated – 2006 to 2010, 2011 to 2013 and 2014 to 2017 – the median (interquartile range [IQR]) age at initiation of ART, which the authors say is a surrogate of prior diagnosis, decreased from first to last: 20.4 (9.4-36.0) to 19.2 (8.8- 33.7) months.
Patients were also nearly twice their age in the low-income countries versus the upper-middle-income countries when they started ART, with a median (IQR) of 24.2 (13.5-39.1) versus 13, 2 (4.7-26.8) months, and the percentage of children who started ART before their first birthday were more than twice as high in upper-middle-income countries versus lower-middle-income, low-income countries:
Upper middle income: 47.4% Lower middle income: 20.9% Low income: 21.7%
The median (IQR) CD4 rate at the start of ART increased by 25% over the study periods: from 16% (11% -22%) in 2006-2010 to 20% (13% -28%) in 2014-2017.
In addition, despite nearly doubling the onset rates of ART among children under 3 months from 2006-2010 to 2014-2014 (5.1% to 10.0%), there was a 26.1% decrease to the same extent in patients with severe immunosuppression (evaluated with CD4 rates) between the same periods, and the total number of children on ART decreased from 14,943 to 7,290.
Overall, by 24 months after the start of the ART, mortality decreased from 6.5% to 2.9% despite the above median (IQR) of 20.5% (20.1% -21.0%) losing had gone for follow-up – which in itself was lower in upper middle income (14.3%) versus low-income countries (21.5%).
And multivariate analysis points to a decrease in mortality among those who recently started ART (2011-2013: adjusted HR [aHR]0.70; 95% CI, 0.63-0.79; 2014-2017: aHR, 0.53; 95% CI, 0.45-0.72 vs. 2006-2010) and people living in upper middle-income countries (aHR, 0.42; 95% CI, 0.35-0.49 vs. low-income countries).
Factors identified as increasing the overall mortality risk were living in lower middle income countries (aHR, 1.26, 95% CI, 1.09-1.44), severe immunosuppression at ART baseline (aHR, 1.54, 95% CI, 1.30-1.82) and underweight (aHR, 1.72, 95% CI, 1.47-2.01).
A total of 5.1% (95% CI, 4.8% -5.3%) died during the study period, and mortality was shown to increase with age at initiation of ART.
“Sub-Saharan Africa is home to about 80% of the 1.8 million children living with HIV worldwide,” the authors emphasize. “However, the scaling-up of routine pediatric care programs in sub-Saharan Africa lags behind HIV care for adults and many still have advanced disease and are still at high risk of premature death or dropout.”
They emphasize that their findings demonstrate the immense, ever-present need for focused efforts to support earlier diagnosis and treatment efforts, especially in patients less than 3 months of age, mothers and pregnant women. Also, 25% of the children evaluated were in advanced stages of the disease in the last study period of 2014-2017 when they enrolled for ART initiation.
“There is still a need to pay more attention to sustainable approaches to better acceptance of early childhood diagnosis in children, early ART initiation, and engagement and maintenance of care for young children living with HIV,” the authors conclude. “Our findings reveal an ongoing loss to follow-up and significant heterogeneity across the country’s income groups.”
Iyun V, Technai KG, Vinikoor M, et al. Variations in the characteristics and outcomes of children with HIV after universal ART in sub-Saharan Africa (2006-17): a retrospective cohort study. Lancet HIV. Published online April 28, 2021.doi: 10.1016 / S2352-3018 (21) 00004-7