“
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

Across sub-Saharan Africa, 200 million people are infected with the bacterium causing TB. Globally, in 2017, an estimated 1.6 million people (300,000 of them with HIV infections) died of TB.

It is not practical to treat all those with TB infections. Unfortunately, it is not easy to identify those likely to develop active TB disease. With current methods, 25–50 people would need to be treated to prevent one case, which would not be a good use of resources. However, new biomarkers are emerging that may allow those on the pathway to active disease to be identified and treated.

The PreFIT project is evaluating a range of tests that individually or collectively hold promise as potential tools to identify those destined to develop active TB. The project team has analysed the product pipeline and selected the most promising products with potential to be introduced in the region. These include a version of the widely used Xpert diagnostic platform, Predict3, based on a three-gene signature associated with transition to active TB disease.

Alongside Predict3, two other simple tests are being assessed – a cheap test for C-reactive protein (CRP) based on fingerprick blood samples and a point-of-care test for haemoglobin. By evaluating the devices in the same study, the project will be able to determine if combinations of tests offer improved performance, generating cost-optimised algorithms for diagnosis.

The project team includes representatives from the Foundation for Innovative New Diagnostics (FIND), who bring wide-ranging expertise in diagnostic development and are advising on the generation of ‘admissible evidence’ for WHO endorsement. Also involved in the project are two EDCTP-funded Regional Networks of Excellence, TESA (Southern Africa) and EACCR (East Africa), which will provide connections to local policymakers and offer the potential of accelerated translation into practice. 

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 PreFIT project will provide key data on the use of urgently needed new diagnostic tools for TB. Based on the performance of the tools, the project team suggests that the number needed to be tested to prevent a case of TB could be as low as five, which would likely make introduction highly cost-effective. Use of the tools would support more targeted treatment, reducing unnecessary use of drugs, and improve the efficiency of preventive treatment. It is estimated that active case finding and preventive treatment could reduce the incidence of TB by 40–90%. A 40% cut would reduce the number of TB patients by 1 million and deaths by 265,000 a year.

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