“
test the safety and efficacy of this new formulation in young children

”

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 remains the leading cause of death in sub-Saharan Africa, accounting for more than 400,000 lives every year. Sensitive and rapid point-of-care tests could ensure that more people begin timely treatment, but currently used tests have so far had limited impact.

However, a new wave of improved diagnostics are beginning to be introduced. A key challenge is not only to assess their performance in real-life settings, but also to determine how they can best be deployed in existing health systems.

Professor Grant Theron is an emerging authority on TB diagnostics. He was part of the team that demonstrated the practicability of the Xpert molecular diagnostic platform, informing WHO recommendations on its use. However, he also played a key role in highly influential EDCTP-funded studies revealing that, in practice, Xpert had less impact than expected because clinicians’ treatment choices were only partly based on diagnostic results – emphasising the importance of understanding the context in which diagnostic tests are used.

In his EDCTP Senior Fellowship, Professor Theron is undertaking a range of studies on a new generation of Xpert-based and other TB diagnostics. These include studies of the performance and impact of Xpert Ultra and AlereQ TB point-of-care testing for pulmonary TB in clinics, as well as the potential to use automated digital chest radiography to optimise the use of molecular tests.

A second study will assess the impact and accuracy of Xpert Ultra and AlereQ TB testing for extra-pulmonary TB in a hospital setting. A third study is focusing on next-generation tests to detect drug resistance, MTBDRsl v2.0 and Xpert XDR, using laboratory samples. These tests have the advantage that they can be performed directly on patient specimens, removing the need for time-consuming culture.  

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.

Professor Theron’s Senior Fellowship will provide key evidence from a high-burden setting on both the performance and the impact of potentially highly significant new tools for TB diagnosis, including how they can be optimally used, for example with other technologies such as radiography. Findings will be of great relevance to policymakers considering whether to implement the new technologies.

The project will also create a biobank of well-characterised samples to serve as a platform for future research, including the training of new researchers. At least three PhD students will be trained as part of the project, building capacity in a priority area for sub-Saharan Africa.

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