“
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

It is estimated that around 3.6 million cases of active TB disease are not detected every year. This means that people fail to get the treatment they need, and also continue to transmit TB to others.

WHO recommends that active attempts are made to identify TB cases in the community, focusing on high-risk groups such as household contacts, those likely to be exposed, and hard-to-reach groups with less access to healthcare facilities. Implementing and expanding this active case-finding strategy requires sensitive and rapid tests to identify potential cases.

The TB TRIAGE + project team is comparing two possible technologies for active case-finding. The first is an innovative X-ray analysis system, based on machine learning, that has proven highly effective at detecting TB in chest X-rays. The portable platform, CAD4TB, rapidly generates accurate results.

The second approach is based on readily available tests that detect C-reactive protein (CRP), a marker of infection. These are affordable and easy to use at point-of-care.

The project team is organising two studies to evaluate these options. The first, TB TRIAGE + -ACCURACY, aims to evaluate the performance of CAD4TB and CRP testing in sub-Saharan African settings, with tests on 1,400 presumptive TB patients in Lesotho and KwaZulu Natal. The study will also determine appropriate cut-offs for diagnosis of TB in these groups.

The second study, TB TRIAGE + -RCT, is a very large, community-based clinical trial involving 35,000 participants. Its three arms will compare CAD4TB, CRP testing and standard diagnostic pathways as a control. The aim is to determine the impact of CAD4TB- and CRP-based screening on notification rates, diagnosis and treatment delays, and patient outcomes. Health economic and equity analyses will also be carried out.

The infrastructure established for the project will also support a range of sub-studies, for example to refine the CAD4TB software for diagnosis of other conditions, evaluation of a point-of-care test for CD4 cell counts in people living with HIV, and mapping of risk factors such as diabetes and alcohol use in targeted populations.

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 TB TRIAGE + project will determine the feasibility of using CAD4TB or CRP testing, after clinical screening but before molecular testing with the Xpert system. It has the potential to increase the numbers of people with TB receiving care, but could also lower costs by reducing unnecessary treatment, decreasing demand for molecular testing, and reducing the numbers of drug-resistant infections requiring longer and more intensive treatment.

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