Pediatric HIV Survival Outcomes Continue to Vary in Sub-Saharan Africa

Despite overall survival improvements among pediatric patients living with HIV in sub-Saharan Africa (SSA) following initiation of antiretroviral therapy (ART), 20.5% do not remain engaged in care, report study findings in Lancet HIV.

In addition, marked mortality differences are especially apparent when stratifying by income and when considering the effects of uneven access to and coverage of ART in SSA.

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 outcomes of children living with HIV from single cohorts and in the pre-ART era. Furthermore, we did not find any studies that compared outcomes of young children living with HIV across economic settings.”

Their primary outcomes were mortality and loss to follow-up during ART as affected by different economic settings, with patients younger than 5 years (N = 32,221) from 16 low-, lower-middle-, and upper-middle-income countries in SSA (Benin, Burundi, Côte d’Ivoire, Democratic Republic of the Congo, Ghana, Kenya, Lesotho, Malawi, Mali, Mozambique, Rwanda, South Africa, Togo, Uganda, Zambia, and Zimbabwe) who initiated ART between January 1, 2006, and December 31, 2017.

For the 3 time periods evaluated—2006 to 2010, 2011 to 2013, and 2014 to 2017—the median (interquartile range [IQR]) age when initiating ART, which the authors point out is a surrogate of earlier diagnosis, decreased from the first through the last: 20.4 (9.4-36.0) to 19.2 (8.8-33.7) months.

Patients were also almost twice as old in the low-income vs the upper-middle-income countries when starting ART, at a median (IQR) of 24.2 (13.5-39.1) vs 13.2 (4.7-26.8) months, and the rate of children starting ART before their first birthdays was more than twice as higher in upper-middle-income countries vs lower-middle- and low-income countries:

• Upper-middle-income: 47.4%
• Lower-middle-income: 20.9%
• Low-income: 21.7%

The median (IQR) CD4 percentage when starting ART jumped 25% over the study periods: from 16% (11%-22%) in 2006-2010 to 20% (13%-28%) in 2014-2017.

In addition, despite ART initiation rates nearly doubling among children younger than 3 months from 2006-2010 to 2014-2014—5.1% to 10.0%—there was a 26.1% decrease in the same measure among patients with severe immunosuppression (evaluated with CD4 percentages) between the same periods, and total children initiating ART fell from 14,943 to 7290.

Overall, by the 24-month mark after ART initiation, mortality decreased from 6.5% to 2.9% despite the aforementioned median (IQR) of 20.5% (20.1%-21.0%) who were lost to follow-up—which itself was lower in upper-middle-income (14.3%) vs low-income (21.5%) countries.

And multivariate analysis bears out drops in mortality among those who recently initiated 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 those 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 risk for mortality were living in lower-middle-income countries (aHR, 1.26; 95% CI, 1.09-1.44), severe immunosuppression at ART initiation (aHR, 1.54; 95% CI, 1.30-1.82), and being 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 the older a child was at ART initiation.

“Sub-Saharan Africa is home to approximately 80% of the 1.8 million children living with HIV globally,” the authors highlight. “However, the scale-up of routine paediatric care programmes in sub-Saharan Africa continues to lag behind adult HIV care and many still present with advanced disease and remain at a high risk of early death or attrition.”

They stress that their findings showcase the immense, ever-present need for targeted efforts to buffet earlier diagnosis and treatment efforts, especially among patients younger than 3 months, mothers, and pregnant women. Also, in the final study period of 2014-2017, 25% of the children evaluated were at an advanced stage of disease when presenting for ART initiation.

“There is still a need to increase focus on sustainable approaches for improved paediatric HIV programme uptake of early infant diagnosis, early ART initiation, and engagement and retention in care for young children living with HIV,” the authors conclude. “Our findings reveal persistent loss to follow-up and considerable heterogeneity across country income groups.”

Reference

Iyun V, Technai K-G, Vinikoor M, et al. Variations in the characteristics and outcomes of children living with HIV following 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