7% of children living with HIV in sub-Saharan Africa die in the two years after starting treatment
HIV care attrition is more common in paediatric patients living with HIV; understanding how much of this is mortality-related can help policymakers develop interventions to stop it.
In sub-Saharan Africa, 7% of children living with HIV died in the two years after they started antiretroviral therapy, according to a systematic review and meta-analysis published in BMC Public Health earlier this month.
The aim of the study was to understand the pooled magnitude of mortality of paediatric patients on first-line ART at different follow-up periods, which had previously not been analysed or reported. The results reveal that 3% of children living with HIV on the continent died three months after taking ART, 5% died in the first six months, 6% died by 12 months, and 7% by 24 months.
These high rates of mortality in the first three to six months after children start ART, show that this is a critical time period for programmers and policymakers to develop interventions, curbing these outcomes.
In 2013, another systematic review reported high death rates among paediatric patients in low- and middle-income countries. That year, a test-and-treat policy was recommended for under fives – where all are started on antiretroviral treatment (ART) as soon as possible after they are diagnosed, regardless of CD4 count or disease progression. This was then extended to all people living with HIV in 2016.
This latest systematic review presents new data from observational cohort studies published between January 2014 and June 2018, and includes 51,619 paediatric ART patients among cohorts of children enrolled on ART from 2001 to 2016 in 15 countries in sub-Saharan Africa.
There was considerable variability between studies in the analysis, with most reporting mortality at just one specific time point. The proportion of deaths also varied greatly between locations and was as low as 2% in a study in Ethiopia and 21% in study from South Africa. The previous systematic review suggested rates as high as 26% in Mozambique and as low as 0% in Botswana, which the authors suggest could be the result of different ART enrolment policies in children starting ART before test-and-treat was initiated, and perhaps even after because some countries were slower to adopt. In an additional pooled sub-group analysis,.
The authors suggest that the high death rates in the first six months after stating ART could be linked to immune reconstitution inflammatory syndrome (IRIS children in Western Africa were also slightly worse off than their counterparts in East and Southern Africa). This occurs when the immune response immediately after treatment initiation is so strong that it actually exacerbates existing infections or leads to new ones due to intense inflammation. In a study from South Africa, 21% of children starting ART developed IRIS, and a quarter of deaths in the first six months after ART-initiation was because of IRIS.
A notable limitation of the study is the fact that it only includes documented mortality, which could be underestimated as many children are lost to follow-up. In this review, loss to follow-up ranged from 2.5% to 31.9%, meaning their outcomes are unknown and may include death. Because of this, studies with high loss to follow-up (over 15%) were excluded from the pooled analysis to reduce heterogeneity between studies, although this was found not to have too much impact on the pooled outcomes.
In their conclusion, the authors note that high mortality rates among children starting ART should highlight the need for specific and targeted strategies to reduce mortality in this time – including screening and management of opportunistic infections before ART initiation to limit possible IRIS.