“
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

Mycobacterium tuberculosis (Mtb) is the most common pathogen on the planet, causing 10 million new infections and almost 1.5 million deaths every year, around a third of them in sub-Saharan Africa.

Diagnosis of TB generally relies on analysis of sputum samples, which may be difficult to obtain from children and people with HIV. As a result, confirmation of infection is rare in these groups. This can lead to under-diagnosis and delayed treatment or mis-diagnosis, wasting resources and exposing patients unnecessarily to powerful drugs.

The Stool4TB study team has developed a method for identifying Mtb in stool samples. As Mtb bacteria are transported up the airways in the lungs and enter the gastrointestinal tract, stool samples have long been seen as a potential alternative source of samples for diagnosis, but results to date have been mixed.

The Stool4TB study aims to validate an innovative new approach to diagnosis based on novel methods of stool preparation, DNA extraction and quantification of Mtb numbers using DNA amplification (polymerase chain reaction, PCR) methods.  Preliminary findings suggest that this approach has advantages over other diagnostic methods and increases the number of cases detected.

Importantly, repeated use of the test would provide a way to track responses to treatment, which is highly challenging in these groups of patients.

The Stool4TB study will generate more data on the PCR-based approach in areas with a high burden of TB and HIV in three African countries, assessing its ability to improve confirmation rates and its usefulness for monitoring treatment responses.

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 project will assess the feasibility, usability and acceptability of stool collection from both the patient and the health system perspective. Increasing numbers of peripheral health facilities in sub-Saharan Africa are developing PCR capabilities, so the approach is likely to be technologically feasible. There is also the potential to develop it into a more convenient point-of-care test.

The project will also create a biobank of samples to support additional studies of TB diagnosis or detection of drug resistance in these groups. In addition, it will establish a TB diagnostic network among African countries with a high TB burden, boosting the capacity of sites to carry out clinical studies on children and people living with HIV.

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