Q&A: HIV-related mortality among children and adolescents on antiretroviral therapy

A new analysis examined HIV-related mortality among children and adolescents (aged 0 to 14 years) who have received antiretroviral therapy (ART). Mortality decreased between 2000 and 2020 globally, after adjusting for region, baseline CD4 cell count (an indicator of the strength of the immune system), age, treatment duration, and sex.

However, the mortality risk remains highest among the youngest children, especially those under one 1 year of age, as well as for children who started ART treatment late at low CD4 counts, and within the first six months after initiating it.

Dr. Hmwe Kyu presents findings from this analysis.

Video transcript

This transcript has been lightly revised for clarity.

Why did you carry out this study, and what methods did you use?

We carried out this study because, although many cohort studies have examined mortality among children and young adolescents living with HIV and receiving antiretroviral therapy, or ART, there has not yet been a comprehensive, systematic review synthesizing all these findings. We conducted a systematic review searching PubMed and Embase and used a meta-regression method to analyze mortality data across several dimensions, including region, age, sex, CD4 count – which is an indicator of the strength of the immune system – and treatment duration.

We also performed a sensitivity analysis by restricting our analysis to high-quality studies and found that results were similar, regardless of whether all studies or only those of high quality were included.

What were your key findings?

We found that HIV-related mortality rates among children and young adolescents have decreased over time. However, the mortality risk remains highest among the youngest children, especially those under 1 year of age, as well as for children who started treatment late at low CD4 counts, and within the first six months after initiating it.

Regional differences persist, although these gaps have narrowed over time.

Key factors influencing HIV-related mortality include treatment duration and CD4 counts at treatment initiation. Let’s take a look at the results for male children aged 3 to 4 years in sub-Saharan Africa. In this first chart, we see that when children in the lowest CD4 category received HRT for up to six months, mortality per 100 person-years dropped from more than 30 deaths in central sub-Saharan Africa, shown in light blue, and just over 10 deaths in eastern sub-Saharan Africa, shown in dark blue, in 2000, to less than eight and three deaths, respectively, in 2020. As shown on the x-axis of all charts, as CD4 counts improved, fewer deaths occurred.

When ART was given for 7 to 12 months among children in the lowest CD4 group, deaths fell from a little over six in western sub-Saharan Africa, shown in red, in 2000, to fewer than two in the same region in 2020.

When children in the lowest CD4 group received ART for 13 to 24 months in central sub-Saharan Africa, shown in light blue, mortality rates per 100 person-years fell from under 3 in 2000 to less than 1 in 2020. In southern sub-Saharan Africa, shown in green, the corresponding mortality rates decreased from approximately 0.7 in 2000 to 0.3 per 100 person-years in 2020.

All together, these results demonstrate significant progress in reducing HIV-related mortality among children and reinforce the value of early initiation and long-term retention in care.

How have geographical variations in risk of mortality changed during the period studied?

Geographical variations in HIV-related mortality rates have historically been substantial, although the differences between regions have narrowed over the period from 2000 to 2020.

For example, in 2000, regions such as central and western sub-Saharan Africa had much higher mortality rates compared to other areas. By 2020, these rates had declined and the gap between regions was smaller, although some differences remained.

What do your findings tell us about the best path forward?

Our results suggest that, despite progress, sustained global support is essential to maintain and build on these gains. Strengthening efforts to prevent vertical transmission and ensuring HIV testing for all exposed infants remain critical. Initiating it promptly, ideally at higher CD4 count, along with supporting long-term retention in care and adherence to treatment, is key to improving survival.