“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

More than 200,000 children die from TB every year, and 1 million new cases are reported. However, TB in childhood can be treated effectively – mortality rates are just 1% – suggesting that many children are dying because their TB is never diagnosed.

Unfortunately, TB is hard to diagnose in children. Clinical symptoms are similar to those for other respiratory infections and young children may find it hard to generate a sputum sample for analysis. Furthermore, because of the way that the TB bacterium infects children, sputum samples may contain few bacteria. Reliable new diagnostics suitable for children are thus urgently needed.

The RaPaed TB project has brought together a consortium of experts from different fields to evaluate eight promising new diagnostic approaches for childhood TB. These include TAM-TB, a blood test that showed promise in the EDCTP-funded TB-CHILD project, as well as a version of the Xpert MTB/RIF molecular diagnostic adapted for stool samples. The RaPaed team will also evaluate two LAM-based tests, which detect a component of Mycobacterium tuberculosis in urine known as lipoarabinomannan (LAM); a LAM-based urine test is now recommended by WHO for detection of TB in HIV-infected adults.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The RaPaed TB team anticipates that at least two of these innovative new approaches will prove sufficiently sensitive to attract WHO endorsement. The team’s make-up and project partners are designed to ensure rapid capture of field-relevant results, encompassing experts in child TB clinical research, industry partners developing point-of-care tests, the Foundation for Innovative New Diagnostics (FIND), and national TB control programmes. FIND, which has developed a portfolio of possible technologies, would be well-placed to take forward the WHO submission process for diagnostics achieving sensitive and specific detection of TB in children.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact