“
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 kills more people than any other single microorganism. However, an estimated one in three cases worldwide are never identified, meaning individuals do not get the treatment they need and can continue to pass on infection to others.

Unfortunately, it is difficult to diagnose TB on the basis of symptoms. Other diagnostic methods are often time-consuming or unreliable. Molecular tests show good performance but are expensive. As a result, WHO has prioritised development of ‘triage tests’ that would rapidly identify individuals most likely to have active TB, who could then be referred for confirmatory molecular testing.

With funding from the EDCTP, the TriageTB project team has been searching for host biomarkers that could act as signatures of active TB infections. Its goal is to identify a combination of markers that could form the basis of an easy-to-use dipstick-type point-of-care diagnostic.

In its first EDCTP-funded project, the team identified a six-marker signature that was highly predictive of active TB disease. This was used to develop a potential point-of-care diagnostic with the ability to deliver results within 30 minutes using fingerprick blood samples. Prototype devices achieved a sensitivity of more than 90% and a specificity of 75%. This Multi-Biomarker Test (MBT) was evaluated in the EDCTP-funded ScreenTB project.

The team’s results also suggested that a smaller number of markers, three or four, might give similarly high levels of performance. This would make a test easier to produce – particularly three-marker systems, which could use standard lateral flow assay strips (which can accommodate a maximum of three markers).

The TriageTB project is validating the new tool on a collection of samples from around the world, which is necessary if the test is to have global use. The best performing combination will then be tested on 100 patients from sub-Saharan Africa. Once the design has been finalised, a validation study will be carried out on samples from 600 adult participants from Southern, East and West Africa. 

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 TriageTB project will determine whether MBT use offers a practical additional step in the TB diagnostic pathway. It has the potential to rationalise use of expensive molecular testing, greatly reducing unnecessary testing of those without TB. Moreover, with the chances of TB diagnosis being much higher, and with results available immediately, it is more likely that healthcare workers and patients will adhere to referral procedures following a positive MBT result.

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