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

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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 around 1.5 million people a year. In 2018, 24% of TB cases occurred in sub-Saharan Africa; with 608,000 deaths, the region accounts for 40% of global TB mortality.

Diagnosis of TB is challenging. The most commonly used method, smear microscopy, is not particularly accurate, and laboratory culture is slow and requires special facilities. 

New rapid molecular tests have been developed and are recommended by WHO. These include the Xpert MTB/RIF platform and the so-called line probe assay. However, these tools are often not available at frontline health facilities in low-income settings.

The TWENDE team – ‘twende’ means ‘let’s go’ in Swahili – has developed a new method for detecting Mycobacterium tuberculosis (Mtb) and for assessing responses to treatment, based on detection of Mtb-specific RNA. In EDCTP-funded research related to this technique, known as the molecular bacterial load assay, the team began to explore the practical and health systems factors affecting the introduction of molecular tests for TB.

The TWENDE study has extended this work, used surveys and interviews with multiple stakeholder groups to identify barriers to the implementation of molecular TB diagnostics. Key factors included inadequate financing, procurement difficulties and insufficient human resources. The study developed a model identifying health system, socioeconomic, cultural and other barriers to translation, which will be of wider relevance to the uptake of innovations into health systems.

To help overcome barriers to the translation of research into practice, the TWENDE study has established knowledge transfer centres at four partner institutions in Kenya, Uganda and Tanzania. More than 25 early-career researchers received training on the translation of research into practice, public communication, and commercialisation of research findings. In addition, six events were held to promote dialogue with regional policymakers.

The team has also secured further funding to evaluate implementation of the molecular bacterial load assay in programmatic settings.

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 TWENDE project has generated key data on the reasons for the slow implementation of molecular testing for TB. It has also created an infrastructure that will more generally create stronger links between policymaking and research communities, and promote the uptake of research into practice.

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