“
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

Infections of the central nervous system (CNS) are responsible for 25–30% of HIV-related deaths, with cryptococcal fungal infections alone accounting for up to 20% of such deaths. There is growing evidence, from EDCTP-funded and other trials, that early screening for cryptococcal infections and prompt treatment can save lives, but take-up of diagnostics has so far been limited, in part because of the practical difficulties of implementing new procedures in existing healthcare systems.

The DREAMM project is a product-based implementation study aiming to demonstrate how screening for CNS infections can be introduced into routine care of people with HIV, and the likely benefits this would deliver.

One key aim of the project is to generate data on an upgraded version of a dipstick diagnostic for cryptococcal infections, the CrAG LFA test, a diagnostic dipstick test that is heat-stable, inexpensive, requires minimal training and has been shown to be cost-effective in resource-limited settings. The test provides an indication of the severity of infection and the need for more intensive care.

In collaboration with healthcare staff, the DREAMM team will develop new clinical pathways and decision-making procedures that incorporate use of an upgraded CrAG LFA test and assessment of other possible causes of meningitis. This should facilitate more rapid use of lumbar punctures to confirm infection and faster initiation of treatment.

Once these new procedures have been finalised, staff will be given training in their use. The project will then evaluate whether they reduce the delays in assessment and treatment, and lead to improved survival.

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.

DREAMM has been designed to generate both evidence and resources directly relevant to health policymakers. It will provide a measure of the added value of the upgraded CrAG LFA test used in conjunction with specific patient management algorithms designed for low-resource settings. The study will also produce training and other materials to support implementation elsewhere, enabling the new procedures and diagnostics tools to be readily introduced in other settings.

More generally, the study illustrates how product-based implementation research can provide a stepping stone between clinical trials and routine clinical use, accelerating the introduction of new interventions.

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