“
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

Globally, around 40% of cases of TB are being missed, leading to unnecessary loss of life and providing opportunities for the spread of infection.

Many of these cases are in urban and peri-urban settlements in resource-poor settings. Reducing the numbers of missed TB cases will require a shift from ‘passive’ case finding, waiting for people with symptoms of TB to visit health facilities, to ‘active’ case finding – going out into communities to search for likely cases.

Active case finding is reliant on efficient approaches to diagnose TB infections. In the EDCTP-funded XACT I project, the XACT team showed that Xpert molecular diagnostic technology could provide the foundation for active case-finding programmes. However, the recently developed Xpert Omni system provides additional advantages – notably, portable equipment ideally suited to active case finding.

In the XACT II study, funded by the US National Institutes of Health, the XACT team demonstrated that community-based point-of-care testing for TB was feasible. This approach was based on use of the Xpert Omni system in low-cost panel vans, a highly practical and scalable approach to case finding within communities.

In the XACT III study, the team aims to collect confirmatory data from a larger population – with 17,000 people projected to be screened – in a range of settings in sub-Saharan Africa. The trial will compare Omni-based community testing with Xpert-based laboratory testing of samples; laboratory testing has the advantage that it does not require any new infrastructure, but typically leads to relatively high loss to follow up. The project team will also compare the cost-effectiveness of the two approaches.

The project will also characterise patients with few or no symptoms, for example by genome sequencing of TB isolates and cough aerosol sampling, to provide insights into how such patients contribute to the transmission of TB. This will inform the development of more accurate models of transmission for assessing the impact of case-finding interventions.

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.

Omni-based diagnosis could transform active case finding for TB. The approach being trialled has already been shown to be feasible, practical and low cost, and could readily be introduced in other low-resource settings in sub-Saharan African. Given the enormous financial impact of TB – projected to cost 2.5% of GDP over 15 years, or US$130bn – there is a high likelihood that improved disease control through active case finding will be cost-effective. The project team has already established close links with national and global policymakers, including the Foundation for Innovative New Diagnostics (FIND) and the STOP-TB Partnership, which are awaiting the results of the trial with great interest.    

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