“
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

TB is responsible for almost 1.5 million deaths every year, with sub-Saharan Africa accounting for around a third of them. A major challenge globally is the detection of infection – an estimated 4 million cases go undiagnosed each year, hampering control efforts.

Late diagnosis can lead to additional lung damage, with long-term consequences for patients’ respiratory health, and creates further opportunities for the spread of infection. However, it is becoming increasingly clear that TB infection occurs along a clinical continuum, as low-level sub-clinical infection gradually develops into a more clinically serious and infectious state. Being able to track this transition would provide more opportunities for early intervention.

The ERASE-TB study aims to explore the potential of new molecular approaches to detect early signs of clinical TB. Distinctive gene activity signatures have been identified that correlate with the transition to active disease. However, they are not yet specific enough to be used in clinical practice, as they generate too many false positives.

The ERASE-TB study is simultaneously assessing ten of the most promising candidate tests for identifying incipient TB. The tests encompass a range of detection technologies, assessing immunological, gene transcription and protein markers, as well as automated image processing and analysis of metabolites in urine.

Their performance will be evaluated and compared in more than 2,000 heavily exposed household contacts of people living with TB, who are at high risk of contracting a TB infection and progressing to TB disease. This approach will ensure that the precise timing of TB infection can be determined, so that the precision of diagnostic validation can be enhanced. A biobank of samples will also be created to support the evaluation of future tests.

Based on the data collected, the study team will also develop algorithms to identify the combination of tests that provide the best performance.

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 ERASE-TB project will generate, in a single study, key evidence on multiple potential TB biomarker technologies – a highly efficient way of generating high-quality comparative data. It will also enable the performance of combinations of tests to be assessed. By including commercial and academic test developers in the project team, the study will also have rapid impact on test development. Ultimately, it should accelerate the development of tests filling a key gap in TB diagnosis and facilitate regional and global TB control efforts.

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